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Sample records for skinned murine myocardium

  1. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    International Nuclear Information System (INIS)

    Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

    2016-01-01

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  2. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

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    Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

    2016-03-15

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  3. Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

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    Gibbs-Strauss, Summer L.; Davis, Scott C.; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2008-02-01

    Aminolevulinic Acid (ALA) is a prodrug which can be administered to cells, animals or patients after which it is transformed via the Heme synthesis pathway into the fluorescent molecule Protoporphyrin IX (PpIX). PpIX has been shown to be useful as both a photosensitizer for photodynamic therapy (PDT) and as a fluorescence imaging contrast agent. The ALA-PpIX system not only provides contrast for fluorescence imaging but also gives information about the metabolic activity of the imaged tissue and thus could be useful for monitoring cancer therapy. In the current study skin photobleaching was examined to determine if PpIX fluorescence contrast in malignant brain tumors could be better visualized noninvasively. Red light photobleaching decreased skin PpIX fluorescence and increased the ability to noninvasively quantify PpIX fluorescence in murine gliomas, as in vivo measurements of mean PpIX fluorescence more closely matched ex vivo quantification following skin photobleaching. Three doses of blue light photobleaching (4 J/cm2, 8 J/cm2 and 12 J/cm2) were tested and determined to give similar levels of skin photobleaching as well as a similar window of decreased skin PpIX fluorescence for noninvasive fluorescence imaging following the photobleaching dose administration.

  4. Anti-ageing effects of a new synthetic sphingolipid (K6EAA-L12) on aged murine skin.

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    Jung, Minyoung; Lee, Sanghoon; Park, Hwa-young; Youm, Jong-Kyung; Jeong, Sekyoo; Bae, Jonghwan; Kwon, Mi Jung; Park, Byeong Deog; Lee, Seung Hun; Choi, Eung Ho

    2011-04-01

    Recently, we reported on the anti-ageing effects of K6PC-5. This compound induced keratinocyte differentiation and fibroblast proliferation by increasing sphingosine-1 phosphate synthesis. We performed this study to confirm the anti-ageing effects of new synthetic products (the K6EAA series) derived from K6PC-5 through an amino group induction. Cellular responses such as differentiation, proliferation and calcium mobilization were investigated using cultured human keratinocytes and fibroblasts. Also, we measured the expressions of collagen mRNA and protein using real time RT-PCR and ELISA, respectively. The K6EAA-L12 product, selected by in vitro screening, was evaluated for anti-ageing effects on intrinsically and extrinsically (photo) aged models of hairless mice. In the intrinsically aged murine skin, K6EAA-L12 showed anti-ageing effects by activating collagen synthesis, eventually causing dermal thickening. Also, in the photo-aged skin, the dermal collagen density and dermal thickness were increased. In photo-aged murine skin, K6EAA-L12 increased stratum corneum integrity by increasing corneodesmosome density and improved the barrier recovery rate. However, there were no changes in the expressions of epidermal differentiation maker proteins. In conclusion, topical K6EAA-L12, a new synthetic K6PC-5 derivative, improves intrinsically and extrinsically (photo) aged skin by increasing the collagen density and improving the skin barrier function. © 2011 John Wiley & Sons A/S.

  5. Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions

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    Z.K. Tuong

    2018-06-01

    Full Text Available Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice, and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i the literature findings and ii the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines.

  6. Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

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    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-06-11

    Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.

  7. Mitochondrial complex III defects contribute to inefficient respiration and ATP synthesis in the myocardium of Trypanosoma cruzi-infected mice.

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    Wen, Jian-Jun; Garg, Nisha Jain

    2010-01-01

    In this study, we conducted a thorough analysis of mitochondrial bioenergetic function as well as the biochemical and molecular factors that are deregulated and contribute to compromised adenosine triphosphate (ATP) production in the myocardium during Trypanosoma cruzi infection. We show that ADP-stimulated state 3 respiration and ATP synthesis supported by pyruvate/malate (provides electrons to complex I) and succinate (provides electrons to complex II) substrates were significantly decreased in left ventricular tissue and isolated cardiac mitochondria of infected mice. The decreased mitochondrial ATP synthesis in infected murine hearts was not a result of uncoupling between the electron-transport chain and oxidative phosphorylation and decreased availability of the intermediary metabolites (e.g., NADH). The observed decline in the activities of complex-I, -IV, and -V was not physiologically relevant and did not contribute to compromised respiration and ATP synthesis in infected myocardium. Instead, complex III activity was decreased above the threshold level and contributed to respiratory-chain inefficiency and the resulting decline in mitochondrial ATP synthesis in infected myocardium. The loss in complex III activity occurred as a consequence of cytochrome b depletion. Treatment of infected mice with phenyl-alpha-tert-butyl nitrone (PBN, antioxidant) was beneficial in preserving the mtDNA-encoded cytochrome b expression, and subsequently resulted in improved complex III activity, mitochondrial respiration, and ATP production in infected myocardium. Overall, we provide novel data on the mechanism(s) involved in cardiac bioenergetic inefficiency during T. cruzi infection.

  8. Mismatched regional myocardial uptake between [sup 123]I-BMIPP and [sup 201]Tl SPECT; Comparison between hypertrophic myocardium and dilated myocardium

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    Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Ejima, Junichi; Tsuda, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1992-07-01

    The distribution of a new myocardial fatty acid metabolic agent [sup 123]I-BMIPP was compared in 6 each patients with hypertrophic myocardium (4 cases of hypertensive heart disease and 2 of hypertrophic cardiomyopathy) and dilated myocardium (4 of dilated type of valvular heart disease and 2 of dilated cardiomyopathy) with that of [sup 201]Tl. Mismatched regional myocardial uptake between [sup 123]I-BMIPP and [sup 201]Tl SPECT was observed in all of the hypertrophic myocardium, however no but one in the dilated myocardium. Relative increase or decrease in regional BMIPP from the images of 20 min and to those of 4 h was observed in 3 cases of the hypertrophic myocardium. FDG-PET was performed in 2 cases of the hypertrophic myocardium. The distribution of FDG was different from neither those of BMIPP nor Tl in a hypertrophic cardiomyopathy case with the reserved distribution of BMIPP and Tl. Although more investigations are necessary, we concluded that [sup 123]I-BMIPP is a promising radiopharmaceutical for evaluating myocardial fatty acid metabolism in hypertrophic myocardium. (author).

  9. Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.

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    Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal; Mahmood, Javed; Lindsay, Patricia E; Okunieff, Paul; Doctrow, Susan R; Bristow, Robert G; Hill, Richard P

    2013-08-01

    Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm

  10. Pred-Skin: A Fast and Reliable Web Application to Assess Skin Sensitization Effect of Chemicals.

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    Braga, Rodolpho C; Alves, Vinicius M; Muratov, Eugene N; Strickland, Judy; Kleinstreuer, Nicole; Trospsha, Alexander; Andrade, Carolina Horta

    2017-05-22

    Chemically induced skin sensitization is a complex immunological disease with a profound impact on quality of life and working ability. Despite some progress in developing alternative methods for assessing the skin sensitization potential of chemical substances, there is no in vitro test that correlates well with human data. Computational QSAR models provide a rapid screening approach and contribute valuable information for the assessment of chemical toxicity. We describe the development of a freely accessible web-based and mobile application for the identification of potential skin sensitizers. The application is based on previously developed binary QSAR models of skin sensitization potential from human (109 compounds) and murine local lymph node assay (LLNA, 515 compounds) data with good external correct classification rate (0.70-0.81 and 0.72-0.84, respectively). We also included a multiclass skin sensitization potency model based on LLNA data (accuracy ranging between 0.73 and 0.76). When a user evaluates a compound in the web app, the outputs are (i) binary predictions of human and murine skin sensitization potential; (ii) multiclass prediction of murine skin sensitization; and (iii) probability maps illustrating the predicted contribution of chemical fragments. The app is the first tool available that incorporates quantitative structure-activity relationship (QSAR) models based on human data as well as multiclass models for LLNA. The Pred-Skin web app version 1.0 is freely available for the web, iOS, and Android (in development) at the LabMol web portal ( http://labmol.com.br/predskin/ ), in the Apple Store, and on Google Play, respectively. We will continuously update the app as new skin sensitization data and respective models become available.

  11. The comparison of nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201Tl re-injection imaging to detect viable myocardium

    International Nuclear Information System (INIS)

    Gao Zhou; Shi yu; Chen Hongyan; Jia Shaowei

    2002-01-01

    Objective: Employing the differences in physical properties of 99m Tc-MIBI and 201 Tl, the authors discuss the contrast result of nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging to detect viable myocardium so that authors can enhance the image quality and shorten the examination time. Method: 34 OMI patients took the 99m Tc-MIBI and 201 Tl dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging respectively in two weeks. During the peak of normal dipyridamole stress i.v. 201 Tl 100 MBq was given and myocardium imaging was taken 15 min later. The dual-isotope group was given nitroglycerin 1mg under the tongue. Five min later, i.v. 99m Tc-MIBI 1110 mBq was given. In 201 Tl re-injection group i.v. 201 Tl 40 MBq was given 4 hour later and were imaged. Among the 34 OMI patients, 19 patients undertook another 99m Tc-MIBI static imaging. Results: There are no obvious differences between nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging in detection rate of viable myocardium, χ 2 =0.823, p>0.25. But they have great difference in perfusion changed sectional myocardium absorb rate, t=2.73, p 2 =27.867, p 201 Tl re-injection imaging

  12. Gene Expression Networks in the Murine Pulmonary Myocardium Provide Insight into the Pathobiology of Atrial Fibrillation

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    Jordan K. Boutilier

    2017-09-01

    Full Text Available The pulmonary myocardium is a muscular coat surrounding the pulmonary and caval veins. Although its definitive physiological function is unknown, it may have a pathological role as the source of ectopic beats initiating atrial fibrillation. How the pulmonary myocardium gains pacemaker function is not clearly defined, although recent evidence indicates that changed transcriptional gene expression networks are at fault. The gene expression profile of this distinct cell type in situ was examined to investigate underlying molecular events that might contribute to atrial fibrillation. Via systems genetics, a whole-lung transcriptome data set from the BXD recombinant inbred mouse resource was analyzed, uncovering a pulmonary cardiomyocyte gene network of 24 transcripts, coordinately regulated by chromosome 1 and 2 loci. Promoter enrichment analysis and interrogation of publicly available ChIP-seq data suggested that transcription of this gene network may be regulated by the concerted activity of NKX2-5, serum response factor, myocyte enhancer factor 2, and also, at a post-transcriptional level, by RNA binding protein motif 20. Gene ontology terms indicate that this gene network overlaps with molecular markers of the stressed heart. Therefore, we propose that perturbed regulation of this gene network might lead to altered calcium handling, myocyte growth, and contractile force contributing to the aberrant electrophysiological properties observed in atrial fibrillation. We reveal novel molecular interactions and pathways representing possible therapeutic targets for atrial fibrillation. In addition, we highlight the utility of recombinant inbred mouse resources in detecting and characterizing gene expression networks of relatively small populations of cells that have a pathological significance.

  13. Myocardium tracking via matching distributions.

    Science.gov (United States)

    Ben Ayed, Ismail; Li, Shuo; Ross, Ian; Islam, Ali

    2009-01-01

    The goal of this study is to investigate automatic myocardium tracking in cardiac Magnetic Resonance (MR) sequences using global distribution matching via level-set curve evolution. Rather than relying on the pixelwise information as in existing approaches, distribution matching compares intensity distributions, and consequently, is well-suited to the myocardium tracking problem. Starting from a manual segmentation of the first frame, two curves are evolved in order to recover the endocardium (inner myocardium boundary) and the epicardium (outer myocardium boundary) in all the frames. For each curve, the evolution equation is sought following the maximization of a functional containing two terms: (1) a distribution matching term measuring the similarity between the non-parametric intensity distributions sampled from inside and outside the curve to the model distributions of the corresponding regions estimated from the previous frame; (2) a gradient term for smoothing the curve and biasing it toward high gradient of intensity. The Bhattacharyya coefficient is used as a similarity measure between distributions. The functional maximization is obtained by the Euler-Lagrange ascent equation of curve evolution, and efficiently implemented via level-set. The performance of the proposed distribution matching was quantitatively evaluated by comparisons with independent manual segmentations approved by an experienced cardiologist. The method was applied to ten 2D mid-cavity MR sequences corresponding to ten different subjects. Although neither shape prior knowledge nor curve coupling were used, quantitative evaluation demonstrated that the results were consistent with manual segmentations. The proposed method compares well with existing methods. The algorithm also yields a satisfying reproducibility. Distribution matching leads to a myocardium tracking which is more flexible and applicable than existing methods because the algorithm uses only the current data, i.e., does not

  14. Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

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    Mao-Qiang Man

    2012-01-01

    Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

  15. Reirradiation of healing murine skin

    International Nuclear Information System (INIS)

    Terry, N.H.A.; Aldana, M.W.; Travis, E.L.

    1987-01-01

    The most common way of assessing residual radiation damage in a tissue has been to retreat at a fixed time interval after a first treatment. Previous studies in skin have shown that the greatest proportion of remembered dose (20-40%) was seen if the retreatment interval was one month, shortly after the acute reaction caused by the first treatment has subsided. Moreover, the observed state of the foot at retreatment depended on the size of the first dose. After a priming dose of 22.5 Gy, the peak skin reaction of 0.8 returned to zero by Day 27. On retreatment at Day 30, the foot was indistinguishable from controls. After higher first doses, the feet still had significant reaction scores ranging from 0.5 to more than 1.0. Thus, in this present study, feet were retreated at a common level of healing rather than after a fixed time interval. Mice feet were irradiated with a range of X-ray doses (22.5-37.5 Gy) covering the threshold to full response. The feet were reirradiated when their skin reactions had fallen to a common value of 0.5. The time of this retreatment was therefore earlier (13 days) after the lowest priming dose (22.5 Gy) than after higher doses. In these latter instances retreatment times ranged from 18-40 days. These data are compared with those from schedules where the second irradiations were performed a fixed time after the first treatment

  16. FTY720 ameliorates murine sclerodermatous chronic graft-versus-host disease by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin.

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    Huu, Doanh Le; Matsushita, Takashi; Jin, Guihua; Hamaguchi, Yasuhito; Hasegawa, Minoru; Takehara, Kazuhiko; Fujimoto, Manabu

    2013-06-01

    Sphingosine 1-phosphate (S1P) exerts a variety of activities in immune, inflammatory, and vascular systems. S1P plays an important role in systemic sclerosis (SSc) pathogenesis. Regulation of S1P in fibrotic diseases as well as in SSc was recently reported. FTY720, an oral S1P receptor modulator, has been shown to be a useful agent for the prevention of transplant rejection and autoimmune diseases. Murine sclerodermatous chronic graft-versus-host disease (GVHD) is a model for human sclerodermatous chronic GVHD and SSc. We undertook this study to investigate the effects of FTY720 in murine sclerodermatous chronic GVHD. FTY720 was orally administered to allogeneic recipient mice from day 0 to day 20 (short-term, early-treatment group), from day 0 to day 42 (full-term, early-treatment group), or from day 22 to day 42 (delayed-treatment group) after bone marrow transplantation. Delayed administration of FTY720 attenuated, and early administration of FTY720 inhibited, the severity and fibrosis in murine sclerodermatous chronic GVHD. With early treatment, FTY720 induced expansion of splenic myeloid-derived suppressor cells, Treg cells, and Breg cells. Vascular damage in chronic GVHD was inhibited by FTY720 through down-regulating serum levels of S1P and soluble E-selectin. FTY720 inhibited infiltration of immune cells into skin. Moreover, FTY720 diminished the expression of messenger RNA for monocyte chemotactic protein 1, macrophage inflammatory protein 1α, RANTES, tumor necrosis factor α, interferon-γ, interleukin-6 (IL-6), IL-10, IL-17A, and transforming growth factor β1 in the skin. FTY720 suppressed the immune response by promoting the expansion of regulatory cells and reducing vascular damage and infiltration of immune cells into the skin. Taken together, these results have important implications for the potential use of FTY720 in the treatment of sclerodermatous chronic GVHD and SSc in humans. Copyright © 2013 by the American College of Rheumatology.

  17. Substrate use in ischemic and reperfused canine myocardium: quantitative considerations

    International Nuclear Information System (INIS)

    Myears, D.W.; Sobel, B.E.; Bergmann, S.R.

    1987-01-01

    The patterns of use of substrate in reperfused myocardium are not yet well elucidated, and their delineation is essential for adequate interpretation of results of analyses performed after positron emission tomography with labeled substrates to differentiate normal from abnormal heart muscle. Accordingly, in open-chest, anesthetized dogs the authors measured glucose and fatty acid utilization in normal, ischemic, and reperfused myocardium and assessed the contributions of metabolism of each substrate to overall oxidative metabolism. Intracoronary [ 3 H]glucose and [ 14 C]palmitate were administered in five control dogs, eight dogs subjected to 1 h of coronary occlusion, and nine dogs subjected to reperfusion after 1 h of ischemia. Regional coronary venous blood samples were assayed sequentially. In reperfused myocardium, utilization of glucose was 103% greater than that in ischemic and 273% greater than in normal myocardium. Utilization of fatty acid during reperfusion, although greater than that in ischemic myocardium, was significantly less than that in normal myocardium despite restoration of flow to 80% of control values. Despite diminished net uptake of fatty acid, oxidation of fatty acid accounted for 63% of total oxygen consumption in reperfused myocardium. These studies indicate that canine myocardium reperfused after 1 h of ischemia exhibits enhanced uptake of glucose and impaired utilization of palmitate. Nevertheless, palmitate continues to comprise the substrate primarily utilized for oxidative metabolism

  18. Abnormal mitochondrial respiration in failed human myocardium.

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    Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N

    2000-12-01

    Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.

  19. Contribution to the study of thallium 201 myocardium scintigraphy

    International Nuclear Information System (INIS)

    Annweiler, Marc.

    1976-01-01

    In this work a new isotope was tested in the field of myocardium scintigraphy: thallium 201. The different radioisotopes used so far in myocardium scintigraphy are reviewed to begin with. The main biological and physical characteristics of thallium and the scintillation camera used for this work are described next. In our opinion thallium 201 owing to its biological behavior similar to that of potassium and to its physical characteristics, appears as one of the better -if not the best- known tracer suitable for use in myocardium scintigraphy. Its properties are suited to the use of a scintillation camera, which considerably shortens the examination time and thus allows an isotopic exploration of the myocardium from several incidences. The only disadvantage of this cyclotron-produced isotope seems to be its high price which will probably limit its use on a large scale. Fifty thallium 201 myocardium scintigraphs were practised on forty-eight coronary thrombosis patients. From this was established a precise topographic correlation between the electrocardiographic diagnosis and the scintigraph. The two corresponded in 47 cases out of 50. The few disagreements between ECG and scintigraphic results seem to be due either to poor-quality images or to an overall myocardium hypofixation connected with a very extensive necrosis. This means that thallium 201 myocardium scintigraphy is a reliable method of examination in the great majority of cases, giving a direct picture of the heart muscle and its necrotic lesions [fr

  20. Influence of trichloroacetic acid peeling on the skin stress response system.

    Science.gov (United States)

    Kimura, Ayako; Kanazawa, Nobuo; Li, Hong-Jin; Yonei, Nozomi; Yamamoto, Yuki; Furukawa, Fukumi

    2011-08-01

    Although trichloroacetic acid (TCA) peeling is widely applied for cosmetic treatment of photodamaged skin, the entire biological mechanisms have yet to be determined. The skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) products that are locally-generated in response to locally-provided stressors or pro-inflammatory cytokines. This system would restrict tissue damage and restore local homeostasis. To determine the influence of TCA peeling on the SSRS in vitro and in vivo, expressions of POMC, melanocortin receptor 1 (MC1R), CRH and CRH receptor 1 (CRHR1) mRNA were examined by reverse transcription polymerase chain reaction in Pam212 murine keratinocytes, murine plantar and healthy human abdominal skin specimens after TCA treatment. In addition, their protein expressions as well as those of POMC-derived peptides were examined immunohistochemically. After TCA treatment, transient upregulation of POMC and MC1R mRNA expressions was observed in both murine and human skin, as well as in Pam212. Enhanced POMC protein, recovery of once-impaired MC1R protein, and no enhancement of POMC-derived peptide productions were revealed immunohistochemically in both murine and human epidermis. In contrast, neither expression levels of CRH and CRHR1 mRNA nor epidermal protein were enhanced after TCA application in murine and human skin, except for induction of human CRH mRNA expression. These results suggest that TCA activates the SSRS by inducing POMC and MC1R productions of keratinocytes in the CRH-independent manner, and that the biological effects of POMC itself are responsible for the TCA-induced epidermal SSRS activation. © 2010 Japanese Dermatological Association.

  1. Probabilistic derivation of the interspecies assessment factor for skin sensitization.

    NARCIS (Netherlands)

    Bil, W; Schuur, A G; Ezendam, J; Bokkers, B G H

    An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization

  2. Effect of Topical Administration of Fractions and Isolated Molecules from Plant Extracts on Skin Wound Healing: A Systematic Review of Murine Experimental Models

    Directory of Open Access Journals (Sweden)

    Mariáurea Matias Sarandy

    2016-01-01

    Full Text Available Background and Purpose. Skin wound healing is a dynamic process driven by molecular events responsible for the morphofunctional repair of the injured tissue. In a systematic review, we analyzed the relevance of plant fractions and isolates on skin wound healing. By revising preclinical investigations with murine models, we investigated if the current evidence could support clinical trials. Methods. Studies were selected in the MEDLINE/PubMed and Scopus databases according to the PRISMA statement. All 32 identified studies were submitted to data extraction and the methodological bias was investigated according to ARRIVE strategy. Results. The studies demonstrated that plant fractions and isolates are able to modulate the inflammatory process during skin wound healing, being also effective in attenuating the oxidative tissue damage in the scar tissue and stimulating cell proliferation, neoangiogenesis, collagen synthesis, granulation tissue expansion, reepithelialization, and the wound closure rate. However, we identified serious methodological flaws in all studies, such as the high level of reporting bias and absence of standardized experimental designs, analytical methods, and outcome measures. Conclusion. Considering these limitations, the current evidence generated from flawed methodological animal studies makes it difficult to determine the relevance of herbal medicines to treat skin wounds and derails conducting clinical studies.

  3. Infestivity of Demodex canis to hamster skin engrafted onto SCID mice.

    Science.gov (United States)

    Tani, Kenji; Une, Satoshi; Hasegawa, Atsuhiko; Adachi, Makoto; Kanda, Naoko; Watanabe, Shin-ichi; Nakaichi, Munekazu; Taura, Yasuho

    2005-04-01

    We demonstrated that Demodex canis was transferred to skin xenografts of a dog and a hamster onto severe combined immunodeficiency mice. After the transfer of mites, the number of eggs, larvae, nymphs and adult mites per gram of canine and hamster xenografts increased, whereas no live mites were detected on murine allograft. These results indicate that D. canis proliferates in hair follicles of dog and hamster skins but not in murine allograft. Therefore, D. canis may have host preference but not strict host-specificity.

  4. Detection of the myocardium ischemia in scintigraphy

    International Nuclear Information System (INIS)

    Faraggi, M.; Pierquet-Ghazzar, N.; Maunoury, C.

    2005-01-01

    The myocardium scintigraphy (SPECT) gives excellent elements of prognosis allowing to select at the best, the patients having a revascularization, and then an angiography examination. It appears complementary of the coronaries tree imaging and should (in theory) be practised in first in an organisation chart of taking over. In the search of practicable myocardium, the PET with 18 FDG, although being competitive, is more and more forsaken to the MRI profit. In retaliation, the PET with 82 Rb with test of pharmacology stimulation could develop in detection of coronaries disease. (N.C.)

  5. Backscatter and attenuation characterization of ventricular myocardium

    Science.gov (United States)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  6. Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-07-01

    Full Text Available Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

  7. Probability mapping of scarred myocardium using texture and intensity features in CMR images

    Science.gov (United States)

    2013-01-01

    Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

  8. Arachidonic acid metabolism in fibroblasts derived from canine myocardium

    International Nuclear Information System (INIS)

    Weber, D.R.; Prescott, S.M.

    1986-01-01

    Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

  9. The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

    International Nuclear Information System (INIS)

    Trunova, V.A.; Zvereva, V.V.; Okuneva, G.N.; Levicheva, E.N.

    2007-01-01

    It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower

  10. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    Science.gov (United States)

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

  11. Diagnosis of Non-compacted Myocardium of the Left Ventricle in Children

    Directory of Open Access Journals (Sweden)

    I.B. Yershova

    2014-05-01

    Full Text Available The authors presented a review of published literature data on rare congenital abnormalities in children — a non-compacted myocardium of the left ventricle, which refers to unclassified cardiomyopathy. This pathology by the American Heart Association classification relates to genetic cardiomyopathy. Non-compacted myocardium of the left ventricle in children develops due to violation of myocardial induration of the fetus in utero. Diagnosis of the disease is difficult due to the lack of specific clinical signs. The authors also presented a clinical case of non-compacted left ventricular myocardium in 6-year-old girl.

  12. Development of a murine model of acute radiation encephalopathy

    International Nuclear Information System (INIS)

    Xing Yigang; Tang Yamei; Liu Jun; Sun Ying

    2003-01-01

    Objective: To develop a murine model of acute radiation encephalopathy. Methods: A total of 40 rats were subjected to local γ-irradiation to the brain with the dosage of 7 Gy/d for 6 consecutive days. The amount of food intake, hairs and skin of irradiated field, body weight, general activities, CNS symptoms and signs were examined and recorded after irradiation. On day 3, 7, 14 and 30, the brain tissue was removed to observe histopathologic changes. Results: During the first two days after irradiation, the irradiated rats were agitated, and the amount of food intake decreased from day 2 onwards. No serious skin reaction to irradiation was observed. Survived rats had normal activities without any abnormal nervous signs. Histopathologic changes showed slight neuronal degeneration, smaller cell body, red-colored cytoplasm, disappearance of Nissl body, vacuolation, typical cell shrinkage, chromatin condensation and nuclear divergence. On the 14th and 30th days, hypochromatism, loose and reticular necrotic foci were found in some samples. Conclusion: The murine model of acute radiation encephalopathy is useful and practical in radiobiological studies

  13. Effect of synthetic vernix biofilms on barrier recovery of damaged mouse skin

    NARCIS (Netherlands)

    Oudshoorn, M.H.M.; Rissmann, R.; van der Coelen, D.; Hennink, W.E.; Ponec, M.; Bouwstra, J.A.

    2009-01-01

    The aim of this work was to investigate whether topical application of synthetic biofilms supports and accelerates the recovery of the murine skin barrier, disrupted by sequential tape stripping. Therefore, various biofilms were applied topically on disrupted mouse skin to determine which

  14. Characterization of the Structural and Functional Changes in the Myocardium Following Focal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Ojha, Navdeep; Roy, Sashwati; Radtke, Jared; Simonetti, Orlando; Gnyawali, Surya; Zweier, Jay L.; Kuppusamy, Periannan; Sen, Chandan K.

    2015-01-01

    High resolution (11.7T) cardiac magnetic resonance imaging (MRI) and histological approaches have been employed in tandem to characterize the secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (IR). IR induced changes in the myocardium were examined in five separate groups at the following time-points after IR: 1h, 1d, 3d, 7d and 14 d. Infarct volume increased from 1h to 1d post-IR. Over time, loss of myocardial function was observed to be associated with increased infarct volume and worsened regional wall motion. In the infarct region, IR caused a decrease in end-systolic thickness coupled with small changes in end-diastolic thickness, leading to massive wall thickening abnormalities. In addition, compromised wall thickening was also observed in left ventricular regions adjacent to the infarct region. A tight correlation (r2 = 0.86) between measured MRI and triphenyltetrazolium chloride (TTC) infarct volumes was noted. Our observation that until day 3 post-IR, the infarct size as measured by TTC staining and MRI were much larger than the myocyte-silent regions in trichrome or H&E stained sections is consistent with the literature and leads to the conclusion that at such early phase the infarct site contains structurally intact myocytes that are functionally compromised. Over time, such affected myocytes were noted to structurally disappear resulting in consistent infarct sizes obtained from MRI, TTC as well as trichrome and hematoxylin/eosin analyses on day 7 following IR. Myocardial remodeling following IR includes secondary myocyte death followed by loss of cardiac function over time. PMID:18375718

  15. The possibilities of using scale-selective polarization cartography in diagnostics of myocardium pathologies

    Science.gov (United States)

    Ushenko, Yu. A.; Wanchuliak, O. Y.

    2013-06-01

    The optical model of polycrystalline networks of myocardium protein fibrils is presented. The technique of determining the coordinate distribution of polarization azimuth of the points of laser images of myocardium histological sections is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented which characterize distributions of wavelet-coefficients polarization maps of myocardium layers and death reasons.

  16. Promotion of accelerated repair in a radiation impaired wound healing model in murine skin

    International Nuclear Information System (INIS)

    Walker, M.D.

    2000-02-01

    Surgical resection of many tumours following radiotherapy is well established as the preferred approach to eradicating the disease. However, prior irradiation compromises the healing of surgical wounds in 30-60% of cases, depending on the site of treatment. There is a need therefore, to understand the deficit in the repair process and to develop therapeutic interventions that may help address this problem. To this end, the aims of this thesis were to characterise a wound healing model in irradiated murine skin and to investigate the effects of topical- compounds and therapeutic modalities upon this wound healing model. Full-thickness dorsal skin excisions were made within a pre-irradiated area (20Gy) in male Balb/c mice and wounds were made in a corresponding area in control animals. Biopsies were removed for histological and immunohistochemical analysis, whilst wound closure experiments were used to determine effects of topical compounds and therapeutic modalities (Low Intensity Laser Therapy, Therapeutic Ultrasound and Transcutaneous Electrical Nerve Stimulation) upon the rate of repair. X-ray irradiation (20Gy) caused a significant delay in the rate of wound closure, whilst histological results indicated that prior irradiation delays the influx of inflammatory cells, delays wound reepithelialisation and reduces granulation tissue formation and collagen deposition. Macrophage and endothelial cell numbers were found to be significantly lower in the irradiated wounds when compared to unirradiated control wounds. Furthermore, apoptosis was affected by irradiation. Although results failed to support any claimed stimulatory effects of various therapeutic modalities upon wound healing, topical application of glucans were shown to have a slight beneficial effect upon the rate of repair. In conclusion, the observed cellular effects caused by irradiation may be a result of permanent damage to stem cells and their ability to replicate and reproduce. Furthermore, the

  17. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease.

    Science.gov (United States)

    Oji, Vinzenz; Eckl, Katja-Martina; Aufenvenne, Karin; Nätebus, Marc; Tarinski, Tatjana; Ackermann, Katharina; Seller, Natalia; Metze, Dieter; Nürnberg, Gudrun; Fölster-Holst, Regina; Schäfer-Korting, Monika; Hausser, Ingrid; Traupe, Heiko; Hennies, Hans Christian

    2010-08-13

    Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.

  18. Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin.

    Science.gov (United States)

    Li, Zhengxiao; Hu, Lizhi; Elias, Peter M; Man, Mao-Qiang

    2018-02-01

    Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin. To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin. Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter. Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration. Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available OBJECTIVES: To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA first pass and delayed enhancement patterns with histopathological changes. MATERIALS AND METHODS: Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9 and II (n = 9 then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg and gadolinium-based macromolecular agent (P792, 15 µmol/kg, respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF staining were performed for infarct characterization. RESULTS: Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium. CONCLUSIONS: Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd

  20. Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin

    OpenAIRE

    Li, Z; Hu, L; Elias, PM; Man, M-Q

    2018-01-01

    Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.Following topical ...

  1. Anisotropy of the apparent frequency dependence of backscatter in formalin fixed human myocardium.

    Science.gov (United States)

    Hall, C S; Verdonk, E D; Wickline, S A; Perez, J E; Miller, J G

    1997-01-01

    Measurements of the frequency dependence of ultrasonic backscatter are presented for specific angles of insonification for regions of infarcted and noninfarcted human myocardium. A 5-MHz transducer was used to insonify cylindrical cores taken from 7 noninfarcted regions and 12 infarcted regions of the left ventricular free wall of 6 formalin-fixed human hearts explanted because of ischemic cardiomyopathy. The dependence of apparent (uncompensated for diffraction effects and attenuation) backscatter on frequency was approximated by a power-law dependence, magnitude of B(f)2 = afn. Under ideal conditions in a lossless medium, the effect of not compensating for the effects of diffraction and attenuation leads to the value of n to be 2.0 for Rayleigh scatterers while the frequency dependence of the fully compensated backscatter coefficient would be f4. The value of n was determined over the frequency range, 3-7 MHz. Both nonifarcted and infarcted myocardium exhibited anisotropy of the frequency dependence of backscatter, with maxima occurring at angles that were perpendicular to the predominant myofiber direction and minima when parallel to the fibers. Perpendicular insonification yielded results for n of 1.8 +/- 0.1 for noninfarcted myocardium and 1.2 +/- 0.1 for infarcted myocardium while parallel insonification yielded results of 0.4 +/- 0.1 for noninfarcted and 0.0 +/- 0.1 for infarcted myocardium. The functional form of the angle-dependent backscatter is similar for both noninfarcted and infarcted myocardium, although the frequency dependence is clearly different for both tissue states for all angles of insonification. The results of this study indicate that the anisotropy of the frequency dependence of backscatter may play a significant role in ultrasonic imaging and is an important consideration for ultrasonic tissue characterization in myocardium.

  2. Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

    Directory of Open Access Journals (Sweden)

    Jiangwei Ma

    2012-03-01

    Full Text Available Brief episodes of myocardial ischemia-reperfusion (IR employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK, lactate dehydrogenase (LDH and aspartate transaminase (AST activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px and glutathione reductase (GR activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

  3. Pyrophosphate scan of the temporarily ischemized dog myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F.; Novak, J.; Vizda, J.; Kubicek, J.; Kafka, P.; Veverkova, O.

    1981-12-01

    In 9 dogs a transient myocardial ischemia was provoked using complete occlusion of the ramus interventricularis anterior of the left coronary artery. The occlusion was removed after 5, 10 or 15 min. Four hrs after removal of the occlusion a scan of the myocardium was carried out using sup(99m)Tc-labelled pyrophosphate. In 7 out of 9 dogs under study the scan was markedly positive, in 2 dogs negative. ECG demonstrated ischemic changes practically in all dogs; the changes became normal after removal of the occlusion, namely in 5 to 35 min. The histological examination of the tissue demonstrated in all 9 dogs only a slight impairment of the myocardium.

  4. 99m Technetium pyrophosphate myocardium scintigraphy. First results

    International Nuclear Information System (INIS)

    Toussaint, Paul.

    1976-01-01

    99m technetium pyrophosphate myocardium scintigraphy is a very recent examination technique. This work gives the results obtained on 61 patients. As a vector of the isotope, pyrophosphate has the advantage over polyphosphate of a fast bone uptake there it should be stressed that a 90 minute pause is necessary between the intraveinous injection of the isotope and the photographic recording so that the reading is not troubled by the labelled intracardiac blood pool image, an image quality criterion being the estimation of a good costal fixation which in fact appears sooner or later according to the subject. The role of pyrophosphate, chelator of calcium in fixation of the isotope on the myocardium, could be explained by the fast appearance of 'dense bodies', made up of calcium hydroxyapathice crystals, in the mitochondria of myocardium cells having undergone an irreversible necrotic process. The choice of 99 m technetium is based on its ease of use: 6 hour half-life, high-energy pure gamma emission at 140 keV. The fixed image studied under two incidences, front and left anterior oblique, is obtained from mobile images given by the scintillation camera used in connection with a data processing system. Several facts are underlined, explaining the disadvantages, advantages and indications of the method [fr

  5. Myocardium scanning with 201TL-chloride in ischemic heart disease

    International Nuclear Information System (INIS)

    Shejretova, E.; Beloev, J.; Kaloyanova, A.; Trindev, P.

    1979-01-01

    Results of myocardial scanning with 210 TL-chloride in ischemic herart disease are repoorted. An avearge dose of 500 microcurie and antero-posterior or lateral projection scanning with coloured registration are recommended. The scintigraphic pattern of the normal myocardium and the pathological changes, manifested by reduced isotope fixation, depending on the severity of the damage, are described. The diffuse pathological changes in the myocardium in ischemic heart disease are manifested by diffuse hypofixation of the radionuclide. The focal lesions in ischemic heart disease were manifested by characteristic changes: the infarctions of the posterior wall show a relatively clear scanographic picture on antero-posterior projection, with cold or cool zones in the median sections of the myocardium picture. Infarctions of the anterior myocardial wall, depending on how sizable they are, on antero-posterior projection are seen to occupy the lateral and central parts of the heart muscle. In the left oblique projection the pathologic process is projected frontally and centrally. (A.B.)

  6. Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Wiggers, Henrik; Bøtker, Hans Erik

    2009-01-01

    Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM).......Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM)....

  7. The myocardium functional reserve indicators in junior children with recurrent acute upper respiratory tract infection

    Directory of Open Access Journals (Sweden)

    L.S. Ovcharenko

    2017-02-01

    Full Text Available Background. The problem of early diagnosis of cardiovascular diseases in children is relevant throughout the world and in Ukraine, as in childhood the health and quality of life of an adult are formed. The psychoemotional stress in junior children as well as increasingly complicating school curriculum, information overload with electronic gadgets, increased frequency of colds in children cause physical inactivity. In addition, infectious agents have a toxic effect on the myocardium, altering its functional state. All these together adversely affect the formation and development of the cardiovascular and respiratory systems of children. The aim was to study the functional reserve of the myocardium in junior children, depending on the frequency of upper respiratory tract infection (URTI. Materials and methods. The study examined 1109 children aged 6 to 9 years old. The URTI incidence was analyzed depending on the age. In the study, the children were divided into two groups. Group 1 consisted of the children with URTI — 210. Group 2 involved the children with occasional URTI — 899. Results. Among 210 surveyed children with upper respiratory infections 171 schoolboys (81.4 % had reduced functional reserve of the myocardium, which is consistent with findings from other studies. In children aged 7 and 9 years old, the number of reduced functional reserve of the myocardium varies from 70 to 82 % in seven-year children, among the schoolboys aged 6 and 8 years old the incidence of reduced functional reserve of the myocardium increased from 83 to 100 % in six-year children. Conclusions. Children with URTI have a reduced functional reserve of the myocardium. Children with episodic URTI have higher rates of functional reserve of the myocardium, therefore reducing the incidence of URTI will lead to the improvement of the myocardium functional state.

  8. Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

    International Nuclear Information System (INIS)

    Hernandez-Pampaloni, Miguel; Morita, Koichi; Dutka, David P.; Camici, Paolo G.; Bax, Jeroen J.

    2005-01-01

    Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means. One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF ≤40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with 15 O-labelled water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (≥0.6 ml min -1 g -1 ) were classified as stunned, and segments with reduced MBF ( -1 g -1 ) as hibernating if MRG was ≥0.25 μmol min -1 g -1 . Segments with reduced MBF and MRG -1 g -1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 μmol min -1 g -1 as non-transmural scars. Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 μmol min -1 g -1 ) and 233 (39%) reduced MRG (0.16±0.05 μmol min -1 g -1 ). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 μmol min -1 g -1 ) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min -1 g -1 ), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min -1 g -1 and 0.48±0.08 ml min -1 g -1 , respectively), and lowest in transmural scars (0.40±0.14 ml min -1 g -1 , P -1 g -1 vs 0.46±0.20 μmol min -1 g -1 , NS), and lowest in stunned myocardium with reduced MRG and transmural scars

  9. Preliminary applied study of assessment ischemic/viable myocardium by 99Tcm-HL91

    International Nuclear Information System (INIS)

    Liu Gang; Wu Hua

    2004-01-01

    Objective: To investigate the representation of 99 Tc m -HL91 in the ischemic myocardium, evaluate the diagnosis value of 99 Tc m -HL91 on hypoxic but viable myocardium. Methods: Six patients with cardiac infarction all underwent 99 Tc m -MIBI SPECT and 99 Tc m -HL91 SPECT. Average radioactivity of ischemic area and normal area were respectively obtained by ROI (2 x 2 pixels) on heart minor axis of images, And the radioactivity ratios of target (ischemic area)-to-non target(normal area)were calculated. Results: In image of 99 Tc m -HL91 SPECT, two patients who's radioactivity coloboma of 99 Tc m -MIBI image could be filled with 99 Tc m -HL91, four patients were not caught sight of obvious filling up. Conclusion 99 Tc m -HL91 can be selectively uptaken by ischemic and hypoxic but viable myocardium. it combination of 99 Tc m -MIBI SPECT may be good for accurate diagnosis and differentiation of viable myocardium. (authors)

  10. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Kenichi Kumagai

    2016-01-01

    Full Text Available Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis.

  11. Perfusion single photon emission computed tomography of myocardium with 99mTc-tetra-phosmine (Myoview)

    International Nuclear Information System (INIS)

    Khusainova, Sh.K.; Zholdybaj, Zh.; Potapov, A.V.; Karaev, O.S.; Akhmetova, G.R.

    2003-01-01

    The aim of the work is study of diagnostic valuation of myocardium scintigraphy with help of the 99m Tc-tetrophosmin, Myoview in determination of latent coronary blood-circulation destabilization in liquidators of the Chernobyl accident (LChA) and persons living in the Semipalatinsk test site (STS) region. The perfusion myocardium scintigraphy was made to 71 patients (5 women and 66 men) from those - 33 LChA and 37 - residents of STS region. The examination was carried out in 'ADAC Genesys Epic' apparatus (USA). Mean age of the patients was 46.3±2.3 years old. In the result of examination the left ventricle myocardium perfusion reduction on 30 % and more was revealed. The distribution of radiopharmaceutical by the myocardium parts were relatively proportional both with pharmacologic load (ATF, dipiridamol) and the rest in 48 (67.7 %) patients. So, the 99m Tc-tetrophosmin, Myoview pharmaceutical allows with high rate estimate the myocardium perfusion and get a high qualitative images, that permits to identify localization, character and distribution of myocardium perfusion reduction in the revealed areas. In the result of myocardine scintigraphy with the pharmacologic load trial conducting the both the latent coronary blood-circulation destabilization forms and the incoming ones were differentiated

  12. MRI in the diagnosis of non-compacted ventricular Myocardium (NCVM) compared to echocardiography

    International Nuclear Information System (INIS)

    Weiss, F.; Habermann, C.R.; Sievers, J.; Weil, J.; Adam, G.; Lilje, C.; Razek, W.

    2003-01-01

    Purpose: To report the detection of con-compacted ventricular myocardium (NVCM) with MRI compared to echocardiography in 8 patients. Material and methods: Non-compaction of the ventricular myocardium is a congenital disorder characterized by an altered structure of the myocardial wall resulting from an intrauterine arrest in endomyocardial embryogenesis. The morphological findings consist of a prominent meshwork of multiple myocardial trabeculations and deep intertrabecular recesses, communicating with the left ventricular cavity. 8 consecutive patients (mean age 7.3 years) with clinical and echocardiographic signs of NCVM were examined by MRI (1.5 T, Vision, Siemens) in short axis and 2- and 4-chamber views, using T 1 -weighted TSE and Cine-GRE in 6 patients and true FISP sequences in 2 patients. MRI and echocardiography were evaluated for visibility, signs of NCVM and involvement of myocardial wall segments. Thickness was measured for non-compacted and compacted myocardium and the non-compacted to compacted (N/C) ratio calculated. Results: MRI diagnosed 6 of 8 patients of having NCVM. Myocardial thickness as measured by echocardiography and MRI showed a good correlation in compacted myocardium (r = 0.82) and no correlation in non-compacted myocardium (r = 0.4). In 2 cases, non-compacted myocardium was detected, but echocardiography did not reach the N/C ratio > 2 as required to diagnose NCVM in accordance with the criteria found in the literature. Both patients were also misdiagnosed by MRI performed with Cine-GRE. MRI reached a N/C ratio > 2 in only three patients. Newer TruFisp sequences showed no definite advantages. Extent of non-compaction could be visualized correctly with MRI. (orig.) [de

  13. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

    Science.gov (United States)

    Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su-Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

    2016-01-01

    Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling. PMID:27710832

  14. Comparative study between MRI and echocardiography in noncompaction of ventricular myocardium

    International Nuclear Information System (INIS)

    Sun Ziyan; Xia Liming; Wang Chengyuan; Rao Jingjing; Shenyu Weihui

    2007-01-01

    Objective: To investigate the MRI and echocardiography manifestations of noncompaction of ventricular myocardium(NVM) and assess the role of MR1 in the diagnosis of NVM by comparing it with echocardiography. Methods: Fourteen cases of NVM diagnosed by echocardiography were examined with MRI, including scanning of black-blood sequences, double inversion recovery fast spin echo (DIBFSE) and triple inversion recovery fast spin echo (TIRFSE), and white blood sequence: fast imaging employ steady state acquisition (FIESTA). Scanning plane includes short axis view, four-chamber view and long axis view. Results: Both MRI and echocardiography displayed involvement of left ventricles in thirteen cases and involvement of double ventricles in one case. Apexes of heart and the intermedius are commonly affected. MRI showed 54 segments and echocardiography showed 53 segments affected, and there is no significant difference between the capability of MRI and echocardiography (P=1,000). The affected myocardium consisted of two layers: subendocardial noncompacted myocardium and epicardial compacted myocardium, and the ratio measurement of N/C by MRI was 3.37±0.89 and it was 3.19±0.82 by echocardiography. Noncompacted myocardium was characterized by prominent and excessive myocardial trabeculations and deep intratrabecular recesses, in which the blood flow was communicated with the ventricle. One case was complicated with ventricular aneurysm, and coronary arteriography was performed with unremarkable findings. One case underwent heart transplantation because of progressive heart failure, Gross findings demonstrated prominent muscular' trabeculations with deep intratrabecular recesses, which coincided well with MRI findings. Conclusion: The MRI manifestation of NVM is characteristic, and MRI with multiple series and planes is helpful in the diagnose of NVM. Compared with echocardiography, MRI could display the pathological cardiac muscle more clearly, because of its high soft

  15. Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

    Science.gov (United States)

    Rimmbach, Christian; Jung, Julia J.; David, Robert

    2015-01-01

    Treatment of the “sick sinus syndrome” is based on artificial pacemakers. These bear hazards such as battery failure and infections. Moreover, they lack hormone responsiveness and the overall procedure is cost-intensive. “Biological pacemakers” generated from PSCs may become an alternative, yet the typical content of pacemaker cells in Embryoid Bodies (EBs) is extremely low. The described protocol combines “forward programming” of murine PSCs via the sinus node inducer TBX3 with Myh6-promoter based antibiotic selection. This yields cardiomyocyte aggregates consistent of >80% physiologically functional pacemaker cells. These “induced-sinoatrial-bodies” (“iSABs”) are spontaneously contracting at yet unreached frequencies (400-500 bpm) corresponding to nodal cells isolated from mouse hearts and are able to pace murine myocardium ex vivo. Using the described protocol highly pure sinus nodal single cells can be generated which e.g. can be used for in vitro drug testing. Furthermore, the iSABs generated according to this protocol may become a crucial step towards heart tissue engineering. PMID:25742394

  16. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A

    2009-01-01

    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal i......Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo......-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic...... (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...

  17. Analysis of the influence factors on myocardium to liver ratio of 99Tcm-MIBI

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Zhao Xiaoguang; Liu Zilai; Wang Shengcai

    1995-01-01

    The resting myocardial SPECT by different MIBI kits for 113 cases of normal and ischemic heart disease is performed. The preparation of kits, reducing agents, and the time of imaging are checked using myocardium to liver (M/L) ratio as the parameter of myocardium uptake of MIBI. It shows that MIBI uptake of myocardium has no relation with the reducing agents, the time of imaging between 60-120 min, while M/L ratio varied in every individual case. The ratio of M/L has also no relation to the Radiochemical Purity (RCP) as long as RCP is more than 95%

  18. A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.

    Science.gov (United States)

    Bogaert, Lies; Woodham, Andrew W; Da Silva, Diane M; Martens, Ann; Meyer, Evelyne; Kast, W Martin

    2015-09-01

    Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

  19. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.

    Science.gov (United States)

    Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su-Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

    2016-12-01

    Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

    Science.gov (United States)

    Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2017-01-17

    A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested 99m Tc(EDDA)-HYNIC-2C-rhein emerged as a "hot spot" imaging probe that has a potential for rapid imaging of

  1. Antibody-mediated delivery of interleukin 4 to the neo-vasculature reduces chronic skin inflammation.

    Science.gov (United States)

    Hemmerle, Teresa; Zgraggen, Silvana; Matasci, Mattia; Halin, Cornelia; Detmar, Michael; Neri, Dario

    2014-11-01

    The antibody-mediated delivery of cytokines ("immunocytokines") to sites of pathological angiogenesis represents an attractive strategy for the development of innovative biopharmaceuticals, capable of modulating the activity of the immune system in cancer and in chronic inflammatory conditions. Recombinant IL4 has previously been shown to be therapeutically active in patients with psoriasis. The antibody-mediated delivery of this cytokine to sites of chronic skin inflammatory conditions should lead to an improved potency and selectivity, compared to non-targeted IL4. The therapeutic activity of F8-IL4, a fusion protein of the F8 antibody (specific to the alternatively-spliced EDA domain of fibronectin) with murine IL4, was investigated in three immunocompetent mouse models of skin inflammation: two induced by the TLR7/8 ligand imiquimod (in Balb/c and C57BL/6) and one mediated by the over-expression of VEGF-A. The EDA domain of fibronectin, a marker for angiogenesis, is expressed in the inflamed skin in all three models and F8-IL4 selectively localized to inflamed skin lesions following intravenous administration. The F8-IL4 fusion protein mediated a therapeutic benefit, which was superior to the one of a non-targeted version of IL4 and led to increased levels of key regulatory cytokines (including IL5, IL10, IL13, and IL27) in the inflamed skin, while IL2 levels were not affected in all treatment groups. A murine version of etanercept and a murine anti-IL17 antibody were used as positive control in the therapy experiments. Skin inflammatory lesions can be selectively targeted using anti-EDA antibody-cytokine fusion proteins and the pharmacodelivery of IL4 confers a therapeutic benefit by shifting the cytokine balance. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Neurogenic Stunned Myocardium Associated with Acute Spinal Cord Infarction: A Case Report

    Directory of Open Access Journals (Sweden)

    Gillian A. Beauchamp

    2012-01-01

    Full Text Available Introduction. Neurogenic stunned myocardium (NSM is a reversible cardiomyopathy resulting in transient left ventricular apical ballooning presumed to result from catecholamine surge occurring under physiologic stress. Acute spinal cord ischemia is a rare ischemic vascular lesion. We report a case of neurogenic stunned myocardium occurring in the setting of acute spinal cord infarction. Methods. Singe case report was used. Results. We present the case of a 63-year-old female with a history of prior lacunar stroke, hypertension, chronic back pain, and hypothyroidism who presented with a brief episode of diffuse abdominal and bilateral lower extremity pain which progressed within minutes to bilateral lower extremity flaccid paralysis. MRI of the spinal cord revealed central signal hyperintensity of T2-weighted imaging from conus to T8 region, concerning for acute spinal cord ischemia. Transthoracic echocardiogram was performed to determine if a cardiac embolic phenomenon may have precipitated this ischemic event and showed left ventricular apical hypokinesis and ballooning concerning for NSM. Conclusion. Neurogenic stunned myocardium is a reversible cardiomyopathy which has been described in patients with physiologic stress resulting in ventricular apical ballooning. Our case suggests that it is possible for neurogenic stunned myocardium to occur in the setting of acute spinal cord ischemia.

  3. Ginseng-berry-mediated gold and silver nanoparticle synthesis and evaluation of their in vitro antioxidant, antimicrobial, and cytotoxicity effects on human dermal fibroblast and murine melanoma skin cell lines

    Directory of Open Access Journals (Sweden)

    Jiménez Pérez ZE

    2017-02-01

    Full Text Available Zuly Elizabeth Jiménez Pérez,1 Ramya Mathiyalagan,1 Josua Markus,1 Yeon-Ju Kim,2 Hyun Mi Kang,3 Ragavendran Abbai,1 Kwang Hoon Seo,2 Dandan Wang,2 Veronika Soshnikova,2 Deok Chun Yang1,21Department of Biotechnology and Ginseng Bank, 2Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Republic of Korea; 3Advanced Cosmeceutical Technology R&D Center, Suwon, Republic of KoreaAbstract: There has been a growing interest in the design of environmentally affable and biocompatible nanoparticles among scientists to find novel and safe biomaterials. Panax ginseng Meyer berries have unique phytochemical profile and exhibit beneficial pharmacological activities such as antihyperglycemic, antiobesity, antiaging, and antioxidant properties. A comprehensive study of the biologically active compounds in ginseng berry extract (GBE and the ability of ginseng berry (GB as novel material for the biosynthesis of gold nanoparticles (GBAuNPs and silver nanoparticles (GBAgNPs was conducted. In addition, the effects of GBAuNPs and GBAgNPs on skin cell lines for further potential biological applications are highlighted. GBAuNPs and GBAgNPs were synthesized using aqueous GBE as a reducing and capping agent. The synthesized nanoparticles were characterized for their size, morphology, and crystallinity. The nanoparticles were evaluated for antioxidant, anti-tyrosinase, antibacterial, and cytotoxicity activities and for morphological changes in human dermal fibroblast and murine melanoma skin cell lines. The phytochemicals contained in GBE effectively reduced and capped gold and silver ions to form GBAuNPs and GBAgNPs. The optimal synthesis conditions (ie, temperature and v/v % of GBE and kinetics were investigated. Polysaccharides and phenolic compounds present in GBE were suggested to be responsible for stabilization and functionalization of nanoparticles. GBAuNPs and GBAgNPs showed increased scavenging activity

  4. A Review of Neurogenic Stunned Myocardium

    OpenAIRE

    Biso, Sylvia; Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

    2017-01-01

    Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome bas...

  5. Involvement of activation-induced cytidine deaminase in skin cancer development.

    Science.gov (United States)

    Nonaka, Taichiro; Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Yamamoto, Norio; Asato, Ryo; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro; Kinoshita, Kazuo

    2016-04-01

    Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.

  6. Development of the mechanical properties of engineered skin substitutes after grafting to full-thickness wounds.

    Science.gov (United States)

    Sander, Edward A; Lynch, Kaari A; Boyce, Steven T

    2014-05-01

    Engineered skin substitutes (ESSs) have been reported to close full-thickness burn wounds but are subject to loss from mechanical shear due to their deficiencies in tensile strength and elasticity. Hypothetically, if the mechanical properties of ESS matched those of native skin, losses due to shear or fracture could be reduced. To consider modifications of the composition of ESS to improve homology with native skin, biomechanical analyses of the current composition of ESS were performed. ESSs consist of a degradable biopolymer scaffold of type I collagen and chondroitin-sulfate (CGS) that is populated sequentially with cultured human dermal fibroblasts (hF) and epidermal keratinocytes (hK). In the current study, the hydrated biopolymer scaffold (CGS), the scaffold populated with hF dermal skin substitute (DSS), or the complete ESS were evaluated mechanically for linear stiffness (N/mm), ultimate tensile load at failure (N), maximum extension at failure (mm), and energy absorbed up to the point of failure (N-mm). These biomechanical end points were also used to evaluate ESS at six weeks after grafting to full-thickness skin wounds in athymic mice and compared to murine autograft or excised murine skin. The data showed statistically significant differences (p clinical morbidity from graft loss.

  7. QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

    OpenAIRE

    Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2016-01-01

    Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin ...

  8. Different Levels of Skin Whitening Activity among 3,6-Anhydro-l-galactose, Agarooligosaccharides, and Neoagarooligosaccharides

    Directory of Open Access Journals (Sweden)

    Ji Hye Kim

    2017-10-01

    Full Text Available 3,6-Anhydro-l-galactose (AHG, a major monomeric constituent of red macroalgae (Rhodophyta, was recently reported to possess skin whitening activity. Moreover, AHG-containing oligosaccharides, such as agarooligosaccharides (AOSs and neoagarooligosaccharides (NAOSs, have various physiological activities, including anti-inflammatory, antioxidant, and skin moisturizing effects. In this study, AHG and NAOSs were produced from agarose by enzymatic reactions catalyzed by an endo-type β-agarase, an exo-type β-agarase, and a neoagarobiose hydrolase. In a cell proliferation assay, AHG, AOSs, and NAOSs at 12.5, 25, and 50 μg/mL concentrations did not exhibit cytotoxicity toward murine B16 melanoma cells or human epidermal melanocytes. In an in vitro skin whitening activity assay of AHG, AOSs, and NAOSs at 50 μg/mL, AHG showed the highest skin whitening activity in both murine B16 melanoma cells and human epidermal melanocytes; this activity was mediated by the inhibition of melanogenesis. Neoagarotetraose and neoagarohexaose also exhibited in vitro skin whitening activity, whereas neoagarobiose and AOSs with degrees of polymerization of 3 (agarotriose, 5 (agaropentaose, and 7 (agaroheptaose did not. Therefore, AHG is responsible for the skin whitening activity of agar-derived sugars, and the structural differences among the AHG-containing oligosaccharides may be responsible for their different skin whitening activities.

  9. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    International Nuclear Information System (INIS)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J.; Mongillo, Marco; Khan, Muhammad T.; Depre, Christophe; Rimoldi, Ornella E.; Camici, Paolo G.

    2007-01-01

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([ 11 C]meta-hydroxy-ephedrine; HED) and β-adrenoceptor (β-AR) density ([ 11 C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V d ) of HED in HM (47.95±28.05 ml/g) and infarcted myocardium (42.69±25.76 ml/g) was significantly reduced compared with controls (66.09±14.48 ml/g). The V d of HED in normal myocardium (49.93±20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial β-AR density was significantly lower in HM (5.49±2.35 pmol/g), infarcted (4.82±2.61 pmol/g) and normal (5.86±1.81 pmol/g) segments of patients compared with healthy controls (8.61±1.32 pmol/g). Noradrenaline uptake-1 mechanism and β-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  10. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    Energy Technology Data Exchange (ETDEWEB)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Mongillo, Marco; Khan, Muhammad T. [Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); Depre, Christophe [University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, New Jersey, NJ (United States); University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Medicine, New Jersey, NJ (United States); Rimoldi, Ornella E. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); New York Medical College, Cardiovascular Research Institute, Department of Medicine, Valhalla, NY (United States); Camici, Paolo G. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom)

    2007-12-15

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([{sup 11}C]meta-hydroxy-ephedrine; HED) and {beta}-adrenoceptor ({beta}-AR) density ([{sup 11}C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V{sub d}) of HED in HM (47.95{+-}28.05 ml/g) and infarcted myocardium (42.69{+-}25.76 ml/g) was significantly reduced compared with controls (66.09{+-}14.48 ml/g). The V{sub d} of HED in normal myocardium (49.93{+-}20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial {beta}-AR density was significantly lower in HM (5.49{+-}2.35 pmol/g), infarcted (4.82{+-}2.61 pmol/g) and normal (5.86{+-}1.81 pmol/g) segments of patients compared with healthy controls (8.61{+-}1.32 pmol/g). Noradrenaline uptake-1 mechanism and {beta}-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  11. Major differences between human atopic dermatitis and murine models as determined by global transcriptomic profiling

    DEFF Research Database (Denmark)

    Ewald, David Adrian; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky...

  12. Free Radical Oxidation in Rat Myocardium after Maximum Permissible Hepatic Resection.

    Science.gov (United States)

    Ermolaev, P A; Khramykh, T P; Barskaya, L O

    2016-03-01

    Free radical oxidation in rat myocardial homogenate was studied by chemiluminescent assay during the early terms after maximum permissible liver resection. During this period, activation of free radical oxidation was biphasic. The critical terms characterized by dramatic intensification of free radical oxidation in the myocardium are the first hour and the first day after surgery. The period from 3 to 12 h after surgery, in which the indices of chemiluminescence decrease, can be tentatively termed as the period of "putative wellbeing". Normalization of the free radical oxidation processes in the myocardium occurred by day 7 after surgery.

  13. Review of the emerging role of optical polarimetry in characterization of pathological myocardium.

    Science.gov (United States)

    Ahmad, Iftikhar

    2017-10-01

    Myocardial infarction (MI), a cause of significant morbidity and mortality, is typically followed by microstructural alterations where the necrotic myocardium is steadily replaced with a collagen scar. Engineered remodeling of the fibrotic scar via stem cell regeneration has been shown to improve/restore the myocardium function after MI. Nevertheless, the heterogeneous nature of the scar patch may impair the myocardial electrical integrity, leading to the formation of arrhythmogenesis. Radiofrequency ablation (RFA) offers an effective treatment for focal arrhythmias where local heating generated via electric current at specific spots in the myocardium ablate the arrhythmogenic foci. Characterization of these myocardial pathologies (i.e., infarcted, stem cell regenerated, and RFA-ablated myocardial tissues) is of potential clinical importance. Optical polarimetry, the use of light to map and characterize the polarization signatures of a sample, has emerged as a powerful imaging tool for structural characterization of myocardial tissues, exploiting the underlying highly fibrous tissue nature. This study aims to review the recent progress in optical polarimetry pertaining to the characterization of myocardial pathologies while describing the underlying biological rationales that give rise to the optical imaging contrast in various pathologies of the myocardium. Future possibilities of and challenges to optical polarimetry in cardiac imaging clinics are also discussed. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  14. Tropical diseases of the myocardium: a review

    Directory of Open Access Journals (Sweden)

    Groom ZC

    2017-04-01

    Full Text Available Zoe C Groom,1 Aristotle D Protopapas,2 Vasileios Zochios3,4 1Costello Medical Consulting Limited, Cambridge, 2Department of Surgery, Division of Surgery and Cancer, Imperial College London, London, 3Department of Intensive Care Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, 4College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK Abstract: Cardiovascular diseases are widely distributed throughout the world. Human parasitic infections are ubiquitous. Tropical parasites are increasingly recognized as causes of cardiovascular diseases. In this review, we address the most frequently reported parasites that directly infect the myocardium, including Trypanosoma cruzi, the protozoal causative agent of American trypanosomiasis (Chagas disease, and Taenia solium, the cestode causative agent of taeniasis and cysticercosis. We also discuss tropical endomyocardial fibrosis, trichinellosis and schistosomiasis. Health systems, attitudes, the perceptions of both patients and physicians as well as socioeconomic factors should all be explored and recognized as crucial factors for improving the control of cardiovascular diseases in the tropics. Clinicians throughout the world must remain aware of imported parasites as potential causes of cardiac diseases. Keywords: cardiomyopathy, Chagas disease, myocardium, parasitic infection, tropical infections

  15. Imaging of the myocardium using {sup 18}F-FDG-PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiří, E-mail: ferda@fnplzen.cz [Clinic of the Imaging Methods, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic); Hromádka, Milan, E-mail: hromadkam@fnplzen.cz [Department of Cardiology, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic); Baxa, Jan, E-mail: baxaj@fnplzen.cz [Clinic of the Imaging Methods, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic)

    2016-10-15

    Highlights: • The natural combination of the metabolic and structural information is the most important strenghtof myocardial PET/MRI. • Metabolic conversion to glycolysis is needed in the assesment ov the viable myocardium. • Metabolic conversion to the fatty acid metabolism is the crucial in the assesment of the ischemic memory and myocardial inflammation. - Abstract: The introduction of the integrated hybrid PET/MRI equipment creates the possibility to perform PET and MRI simultaneously. Depending on the clinical question, the metabolic conversion to glycolytic activity or beta-oxidation is performed before the application of FDG. Since FDG aids to evaluate the energetic metabolism of the myocytes and myocardial MRI reaches the imaging capabilities of perfusion and tissue characterization in the daily routine, FDG-PET/MRI looks to be a promising method of PET/MRI exploitation in cardiac imaging. When myocardial FDG uptake should be evaluated in association with the perfusion distribution, the cross-evaluation of FDG accumulation distribution and perfusion distribution pattern is necessary. The different scenarios may be used in the assessment of myocardium, the conversion to glycolytic activity is used in the imaging of the viable myocardium, but the glycolytic activity suppression might be used in the indications of the identification of injured myocardium by ischemia or inflammation. FDG-PET/MRI might aid to answer the clinical tasks according to the structure, current function and possibilities to improve the function in ischemic heart disease or to display the extent or activity of myocardial inflammation in sarcoidosis. The tight coupling between metabolism, perfusion and contractile function offers an opportunity for the simultaneous assessment of cardiac performance using one imaging modality.

  16. Effects of Ionizing Radiation on Murine Gene Expression in Skin and Bone

    Science.gov (United States)

    Terada, Masahiro; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Alwood, Joshua; Tahimic, Candice; Sowa, Marianne B.; Globus, Ruth K.

    2017-01-01

    Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The potential for exposure to space radiation to contribute to lasting decrements in bone mass is not yet understood. Sustained changes to bone mass have a relatively long latency for development, however skin is a radiation sensitive organ and changes in skin gene expression may serve as an early radiation biomarker of exposures and may correlate with adverse effects on skeletal tissue. Previous studies have shown that FGF18 gene expression levels of hair follicles collected from astronauts on the ISS rose over time. In the hair follicle, FGF18 signaling mediates radioresistance in the telogen by arresting the cell cycle, and FGF18 has the potential to function as a radioprotector. In bone, FGF18 appears to regulate cell proliferation and differentiation positively during osteogenesis and negatively during chondrogenesis. Cellular defense responses to radiation are shared by a variety of organs, hence in this study, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We have examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (TBI). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and TBI (0.5 Gy Fe-56 600 MeV/n and 0.5 Gy H-1 150 MeV/n). Animals were euthanized one and 11 days post-IR. Statistical analysis was performed via a Student's ttest. In skin samples one day after IR, skin expression of FGF18 was significantly greater (3.8X) than sham-irradiated controls (3.8X), but did not differ 11 days post TBI. Expression levels of other radiation related genes (Nfe2l2, Trp53, Cdkn1a, FoxO3

  17. Liposome kinetics in infarcted canine myocardium

    International Nuclear Information System (INIS)

    Caride, V.J.; Twickler, J.; Zaret, B.L.

    1984-01-01

    To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3 H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02)

  18. Effects of isoproterenol on myocardium

    International Nuclear Information System (INIS)

    Barker, M.E.; Lieber, J.G.; Budinger, T.F.

    1982-01-01

    In the course of autoradiographic studies designed to localize 14 C-taurine within the cells of the rat myocardium, severe tissue damage was noted after stimulation by very low levels of isoproterenol. This β-adrenergic agonist had previously been shown by others to modulate taurine uptake by what appeared to be a very specific mechanism, but our studies have led to a different mechanism. Within four hours after injection of isoproterenol at all concentrations used, pronounced edema of myocytes in the subendocardium was noted; this was followed by an inflammatory reation and degeneration of mitochondria and myofilaments

  19. Distinction of salvaged and infarcted myocardium within the ischaemic area-at-risk with T2 mapping

    DEFF Research Database (Denmark)

    Hammer-Hansen, Sophia; Ugander, Martin; Hsu, Li-Yueh

    2014-01-01

    values from T2 maps and signal intensities on T2-weighted images were measured in the corresponding areas. RESULTS: At both imaging time points, the T2 of the salvaged myocardium was longer than of remote (66.0 ± 6.9 vs. 51.4 ± 3.5 ms, P ...AIM: Area-at-risk (AAR) measurements often rely on T2-weighted images, but subtle differences in T2 may be overlooked with this method. To determine the differences in oedema between salvaged and infarcted myocardium, we performed quantitative T2 mapping of the AAR. We also aimed to determine...... (14.7 ± 5.6 vs. 8.7 ± 5.1 ms, P = 0.02). CONCLUSIONS: T2 relaxation parameters are different in the infarcted and salvaged myocardium, and both are significantly longer than remote. Furthermore, the magnitude of increase in T2 was less in the salvaged myocardium after longer reperfusion, indicating...

  20. Modulation of ephrinB2 leads to increased angiogenesis in ischemic myocardium and endothelial cell proliferation

    International Nuclear Information System (INIS)

    Mansson-Broberg, Agneta; Siddiqui, Anwar J.; Genander, Maria; Grinnemo, Karl-Henrik; Hao Xiaojin; Andersson, Agneta B.; Waerdell, Eva; Sylven, Christer; Corbascio, Matthias

    2008-01-01

    Eph/ephrin signaling is pivotal in prenatal angiogenesis while its potential role in postnatal angiogenesis largely remains to be explored. Therefore its putative angiogenic and therapeutic effects were explored in endothelium and in myocardial ischemia. In culture of human aortic endothelial cells the fusion protein ephrinB2-Fc induced cell proliferation (p < 0.0005) and in the murine aortic ring model ephrinB2-Fc induced increased sprouting (p < 0.05). Myocardial infarction was induced by ligation of the left anterior descending artery in mouse. During the following 2 weeks mRNA of the receptor/ligand pair EphB4/ephrinB2 was expressed dichotomously (p < 0.05) and other Eph/ephrin pairs were expressed to a lesser degree. Twenty-four hours after intraperitoneal administration of ephrinB2-Fc it was detected in abundance throughout the myocardium along capillaries, showing signs of increased mitosis. After 4 weeks the capillary density was increased 28% in the periinfarcted area (p < 0.05) to a level not different from healthy regions of the heart where no change was observed. These results implicate that EphB4/ephrinB2 is an important signaling pathway in ischemic heart disease and its modulation may induce therapeutic angiogenesis

  1. Attenuation coefficient of the light in skin of BALB/c and C57BL/6 mice

    Science.gov (United States)

    Silva, C. R.; Camargo, C. F. M.; Aureliano, D. P.; De Pretto, L. R.; Freitas, A. Z.; Ribeiro, M. S.

    2015-06-01

    Optical properties of the biological tissue play an important role to a correct use of optical techniques for therapy and diagnosis. The mice skin presents morphological differences due to characteristics such as gender, body mass and age. Murine models are frequently used in pre-clinical trials in optical therapy and diagnosis. Therefore, the assessment of the skin tissue in animal models is needed for a proper understanding of how light interacts with skin. Noninvasive techniques such as optical coherence tomography (OCT) have been used to obtain optical information of the tissue, as the attenuation coefficient, with the advantage of obtaining sectional images in real time. In this study, eight female BALB/c albino mice (twenty-four weeks old) and eight male C57BL/6 black mice (eight weeks old) were used to measure the attenuation coefficient of the light in the skin, utilizing the OCT technique, aiming to check for influence of the aging process. Two moments were assessed twenty-two weeks apart from each other. Our data show that the aging process significantly affects the light attenuation coefficient in mice skin. Twenty-two weeks after, statistical significant differences were observed between groups within a same strain. We conclude that light attenuation coefficient of mice skin may be influenced by factors such as disorganization of the dermis. Morphological aspects of skin should be taken into account in studies that involve optical strategies in murine models.

  2. T-cell receptor gamma delta bearing cells in normal human skin

    NARCIS (Netherlands)

    Bos, J. D.; Teunissen, M. B.; Cairo, I.; Krieg, S. R.; Kapsenberg, M. L.; Das, P. K.; Borst, J.

    1990-01-01

    T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+

  3. Focalized contractile impairment at hypertrophied myocardium proven in consideration of wall stress in patients with hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Yamazaki, Tadashi; Suzuki, Jun-ichi; Shimamoto, Ryoichi; Tsuji, Taeko; Ohmoto, Yuki; Toyo-oka, Teruhiko; Omata, Masao; Ohtomo, Kuni; Nagai, Ryozo

    2006-01-01

    In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed in spite of impaired systolic function in the hypertrophied myocardium. The aim of the present study was to determine the mechanism of this paradox. Seventeen patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR) imaging to measure percent systolic wall thickening and percent fractional shortening. The ratio of systolic radial wall stress of the LV at the hypertrophied myocardium over that at the nonhypertrophied myocardium was evaluated to describe the focal advantageous condition for wall thickening. The ratio was 0.66±0.36 at the start of contraction and 0.78±0.31 at early-systole, indicating consistently smaller radial wall stress at the hypertrophied myocardium. Although the condition for contraction was favorable (a ratio less than 1.00), percent systolic wall thickening at the hypertrophied myocardium (23.0±11.8%) was smaller than that at the nonhypertrophied myocardium (70.5±32.3%). Smaller end-diastolic dimension (HCM group; 45.2±4.2 mm, reference group; 48.9±4.1 mm, P=0.04) with a statistically identical value of systolic decrease in intraventricular dimension (HCM group; 19.7±3.9 mm, reference group; 18.9±3.2 mm, P=0.60) yielded high percent fractional shortening in patients with HCM (43.5±7.6%). Although contractile impairment was proven at the hypertrophied region with low radial wall stress in the HCM group, the smaller end-diastolic dimension in this group resulted in high percent fractional shortening. (author)

  4. The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

    Directory of Open Access Journals (Sweden)

    M Sofiabadi

    2012-05-01

    Full Text Available

    Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.
    Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 
    Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

    Conclusion: This study showed

  5. Study of rNIS as a reporter gene monitoring rBMSC transplanted to rat myocardium

    International Nuclear Information System (INIS)

    Hu Shou; Lan Xiaoli; Cao Wei; Cao Guoxiang; Zhang Guopeng; Zhang Binqing; Wu Tao; Chang Wei; Zhang Yongxue

    2010-01-01

    Objective: To investigate the feasibility of rat sodium/iodide symporter (rNIS) as a reporter gene monitoring rat bone marrow mesenchymal cells (rBMSC) transplanted to rat myocardium in vivo. Methods: Recombinated adenovirus vector was constructed by rNIS/enhanced green fluorescence protein (EGFP) (Ad-rNIS/EGFP). rBMSC transfected by Ad-rNIS/EGFP were studied using fluorescence microscope. Fifteen rats were transplanted with rBMSC and randomly divided into three groups: rNIS group (with rNIS transfection), blocked group (with rNIS transfection) by oral intake of perchloric sodium before planar imaging (GE Millennium MPR SPECT), and control group (without rNIS transfection). All rats underwent 99 Tc m -pertechnetate planar imaging. The biological distribution of 99 Tc m -pertechnetate was studied. The expressions of rNIS gene and protein in myocardium were measured by real time polymerase chain reaction (PCR) and western blot, respectively. The expressions of CD 29 , CD 44 , CD 90 , CD 11 b, CD 34 and CD 45 were measured by immunohistochemistry. Results: rBMSC transfected by Ad-rNIS/EGFP showed EGFP expression under fluorescence microscope. The transplanted rat myocardium could be visualized on 99 Tc m -pertechnetate planar imaging in rNIS group. The relative uptake ratio (R heart /R hmb , RUR) was 6.7 ±0.4. RUR in control group (3.0 ±0.2) was lower than that in rNIS group (t =2.78, P=0.03). The percentage injection dose per gram of tissue (% ID/g) of the transplanted myocardium was 60.2 ± 20.8 in rNIS group, which was higher than that (2.5 ± 0.4) % ID/g of control group ( t = 7.13, P 29 , CD 44 and CD 90 were positive, CD 45 and CD 45 negative CD 11 b mildly positive in the myocardium transplanted with infective rBMSC. Conclusion: rNIS can efficiently monitor rBMSC transplanted to rat myocardium. (authors)

  6. Genetic modification of stem cells for improved therapy of the infarcted myocardium.

    Science.gov (United States)

    Haider, Husnain Kh; Mustafa, Anique; Feng, Yuliang; Ashraf, Muhammad

    2011-10-03

    The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.

  7. The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium

    International Nuclear Information System (INIS)

    Almeda, Francis Q.; Glock, Dana; Sandelski, Joanne; Ibrahim, Osama; Macioch, James E.; Allen, Trisha; Dainauskas, John R.; Parrillo, Joseph E.; Snell, R. Jeffrey; Schaer, Gary L.

    2004-01-01

    Background: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. Methods: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. Results: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed

  8. In-vivo data on the influence of tobacco smoke and UV light on murine skin.

    Science.gov (United States)

    Pavlou, P; Rallis, M; Deliconstantinos, G; Papaioannou, G; Grando, S A

    2009-01-01

    Inhaled tobacco smoke comes in direct contact with few organs such as mouth, lungs, and stomach. Cigarette smoke (CS) in lungs has been extensively studied. However, limited data exist on its effect on skin, and there are no long-term experimental studies suggesting toxic effects on skin. Even though it is generally accepted that CS is among the main factors of skin aging, the number of experimental studies showing this aging effect is limited. We hereby studied the effect of long-term exposure to CS on the skin of hairless mice in combination with or without ultraviolet (UV) light. In addition, we investigated potential skin protection by a potent antioxidant namely procyanidine-rich French maritime pine bark extract (PBE) pycnogenol. Male and female hairless SKH-2 mice were exposed for 10 months to tobacco smoke and/or UV light in vivo, and their effects on skin were investigated. Some biophysical parameters such as development of erythema, transepidermal water loss (TEWL), and skin elasticity were measured. The results show that UV and CS may be acting synergistically, as shown by the enhanced TEWL, erythema values, epitheliomas, and squamous cell carcinomas (SCCs) observed, whereas PBE seems to protect skin against SCC.

  9. Fractal analysis of phasic laser images of the myocardium for the purpose of diagnostics of acute coronary insufficiency

    Science.gov (United States)

    Wanchuliak, O. Y.; Bachinskyi, V. T.

    2011-09-01

    In this work on the base of Mueller-matrix description of optical anisotropy, the possibility of monitoring of time changes of myocardium tissue birefringence, has been considered. The optical model of polycrystalline networks of myocardium is suggested. The results of investigating the interrelation between the values correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize the distributions of Mueller matrix elements in the points of laser images of myocardium histological sections. The criteria of differentiation of death coming reasons are determined.

  10. Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury

    Science.gov (United States)

    Linares-Palomino, José; Husainy, Muhammad A; Lai, Vien K; Dickenson, John M; Galiñanes, Manuel

    2010-01-01

    Protein kinase B (PKB/Akt) plays a critical role in cell survival but the investigation of its involvement has been limited by the lack of specific pharmacological agents. In this study, using novel PKB inhibitors (VIII and XI), we investigated the role of PKB in cardioprotection of the rat and human myocardium, the location of PKB in relation to mitoKATP channels and p38 mitogen-activated protein kinase (p38 MAPK), and whether the manipulation of PKB can overcome the unresponsiveness to protection of the diabetic myocardium. Myocardial slices from rat left ventricle and from the right atrial appendage of patients undergoing elective cardiac surgery were subjected to 90 min ischaemia/120 min reoxygenation at 37°C. Tissue injury was assessed by creatine kinase (CK) released and determination of cell necrosis and apoptosis. The results showed that blockade of PKB activity caused significant reduction of CK release and cell death, a benefit that was as potent as ischaemic preconditioning and could be reproduced by blockade of phosphatidylinositol 3-kinase (PI-3K) with wortmannin and LY 294002. The protection was time dependent with maximal benefit seen when PKB and PI-3K were inhibited before ischaemia or during both ischaemia and reoxygenation. In addition, it was revealed that PKB is located downstream of mitoKATP channels but upstream of p38 MAPK. PKB inhibition induced a similar degree of protection in the human and rat myocardium and, importantly, it reversed the unresponsiveness to protection of the diabetic myocardium. In conclusion, inhibition of PKB plays a critical role in protection of the mammalian myocardium and may represent a clinical target for the reduction of ischaemic injury. PMID:20403980

  11. Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

    International Nuclear Information System (INIS)

    Fujita, M.; Ohno, A.; Wada, O.; Miwa, K.; Nozawa, T.; Yamanishi, K.; Sasayama, S.

    1991-01-01

    The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 ± 0.5 (SD), which was significantly higher than the 0.7 ± 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area

  12. Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Kawamoto, Masahide; Takahashi, Norio; Yonekura, Yoshiharu; Magata, Yasuhiro; Nohara, Ryuji; Kambara, Hirofumi; Kawai, Chuichi; Konishi, Junji

    1991-01-01

    Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of β-oxydation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65±5 vs 100±29 bpm, p<0.05 and 119±12 vs 144±16 mmHg, p<0.01, respectively). The clearance half-time and the residual fraction were significantly decreased (23.4±2.6 vs 15.8±2.3 min and 67.0±2.5 vs 58.6±4.0%, p<0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that β-oxydation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium. (author)

  13. Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction.

    Science.gov (United States)

    Eid, Refaat A; Zaki, Mohamed Samir Ahmed; Al-Shraim, Mubarak; Eleawa, Samy M; El-Kott, Attalla Farag; Al-Hashem, Fahaid H; Eldeen, Muhammad Alaa; Ibrahim, Hoja; Aldera, Hussain; Alkhateeb, Mahmoud A

    2018-05-01

    This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 μg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

    Directory of Open Access Journals (Sweden)

    Emirhan Nemutlu

    Full Text Available Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK, creatine kinase (CK, and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2, third (18O3, and fourth (18O4 positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic

  15. Kronisk iskaemisk hjerteinsufficiens. Revaskularisering bedrer overlevelsen blandt patienter med hibernating myocardium

    DEFF Research Database (Denmark)

    Holdgaard, Paw Chr; Nielsen, Søren Steen; Wiggers, Henrik

    2007-01-01

    imaging was performed with 99mTc-sestamibi and glucose metabolism was visualized with 18F-fluorodeoxyglucose (18F-FDG) gamma camera PET. Medical records and death certificate were reviewed retrospectively. RESULTS: 50 patients were included. We found an increased survival among patients with HIB who......INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional myocardium (Hibernating myocardium, HIB) can benefit from revascularization. These patients can be selected with nuclear methods. The purpose of this study was to describe the results of the imaging procedures...... in patients tested for HIB and relate the results to the choice of treatment and cause of death. MATERIALS AND METHODS: During a 2-year period 51 patients were referred to determine the amount of HIB. This can be determined with blood flow and metabolic imaging of the heart. Resting-myocardial perfusion...

  16. Multivariate Models for Prediction of Human Skin Sensitization ...

    Science.gov (United States)

    One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens TM assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches , logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine

  17. Bee Venom Phospholipase A2 Alleviate House Dust Mite-Induced Atopic Dermatitis-Like Skin Lesions by the CD206 Mannose Receptor

    OpenAIRE

    Dasom Shin; Won Choi; Hyunsu Bae

    2018-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic, erythematous, and eczematous skin plaques. We previously reported that phospholipase A2 (PLA2) derived from bee venom alleviates AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model. However, the underlying mechanisms of PLA2 action in actopic dermatitis remain unclear. In this study, we showed that PLA...

  18. Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells.

    Science.gov (United States)

    Ma, Hak-Ling; Napierata, Lee; Stedman, Nancy; Benoit, Stephen; Collins, Mary; Nickerson-Nutter, Cheryl; Young, Deborah A

    2010-02-01

    Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor alpha (TNFalpha) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNFalpha blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNFalpha blockade-induced exacerbation of skin inflammation in murine psoriasis-like skin disease. Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RB(high)CD25- (naive CD4) T cells from donor mice. These mice were treated with either anti-interleukin-12 (anti-IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNFalpha. Cytokine gene expression from these differentiated cells was also determined. Neutralization of TNFalpha exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1beta, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNFalpha also demonstrated a divergent role during priming and reactivation of naive T cells. These results reveal a novel immunoregulatory role of TNFalpha on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments.

  19. Antimelanogenic Efficacy of Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) in Melanocytes and Three-Dimensional Human Skin Equivalent.

    Science.gov (United States)

    Lee, John Hwan; Lee, Eun-Soo; Bae, Il-Hong; Hwang, Jeong-Ah; Kim, Se-Hwa; Kim, Dae-Yong; Park, Nok-Hyun; Rho, Ho Sik; Kim, Yong Jin; Oh, Seong-Geun; Lee, Chang Seok

    2017-01-01

    Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy. © 2017 S. Karger AG, Basel.

  20. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  1. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  2. Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

    Science.gov (United States)

    Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven; Motiwala, Shweta R; Addae, Gifty; Manning, Warren J; Nezafat, Reza

    2017-10-01

    To compare remote myocardium native T 1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T 1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T 1 map was performed using a slice interleaved T 1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. The remote myocardium native T 1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P Remote myocardium native T 1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T 1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081. © 2017 International Society for Magnetic Resonance in Medicine.

  3. Staphylococcus aureus α-toxin modulates skin host response to viral infection.

    Science.gov (United States)

    Bin, Lianghua; Kim, Byung Eui; Brauweiler, Anne; Goleva, Elena; Streib, Joanne; Ji, Yinduo; Schlievert, Patrick M; Leung, Donald Y M

    2012-09-01

    Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays. We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P skin inoculated with an α-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin-deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs. The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Angiogenesis with intramyocardial administration of basic fibroblast growth factor in canine ischemic myocardium

    International Nuclear Information System (INIS)

    Sun Lijun; Liu Ying; Zhao Haitao; Huan Yi; Ge Yali; Gao Fabao

    2004-01-01

    Objective: To evaluate the effect of intramyocardial administration of basic fibroblast growth factor on angiogenesis of infarcted myocardium in dogs. Methods: Twenty-four mongrel dogs were randomized into control group and therapeutic group. Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. As soon as coronary artery was occluded, 50 mg of basic fibroblast growth factor in 15 ml of saline was injected into the infarcted and border zone in therapeutic group, whereas 15 ml saline alone was used in the same way in control dogs. Every 3 dogs in each group was studied on the 1 st day, the 3 rd day, the 10 th day, and the 17 th day, respectively. Electron microscope was used to observe the growth of capillaries. Angiogenesis was evaluated by immunohistochemical studies with VIII factor. With sensitivity encoded technique, cine MR and MR perfusion imaging were performed on each dog within 3 hours after surgery and before euthanasia to evaluate cardiac function and the characteristics of myocardial perfusion. Results: In therapeutic group, LVEF improved markedly since the 10 th day (on the 10 th day: control group 24.09 ± 3.32, therapeutic group 45.71 ± 6.27; on the 17 th day: control group 31.46 ± 4.60, therapeutic group 53.46 ± 5.24). Hypoenhancement on first pass and hyperenhancement on delayed phase appeared in infarcted myocardium. There were significant differences for the time of upslope, peak time of signal intensity, upslope curves ratio, and contrast enhancement ratio between infarcted and normal myocardium. The size of infarcted myocardium was markedly decreased on the 17 th day [control group (9.04 ± 1.59)%, therapeutic group (4.07 ± 1.20)%]. The capillaries grew actively in therapeutic group and microvessel density was higher in therapeutic group than in control group except the first day (control group and therapeutic group respectively on the 3 rd day: 92.3 ± 11

  5. Distribution and function of sodium channel subtypes in human atrial myocardium

    NARCIS (Netherlands)

    Kaufmann, Susann G.; Westenbroek, Ruth E.; Maass, Alexander H.; Lange, Volkmar; Renner, Andre; Wischmeyer, Erhard; Bonz, Andreas; Muck, Jenny; Ertl, Georg; Catterall, William A.; Scheuer, Todd; Maier, Sebastian K. G.

    Voltage-gated sodium channels composed of a pore-forming alpha subunit and auxiliary beta subunits are responsible for the upstroke of the action potential in cardiac muscle. However, their localization and expression patterns in human myocardium have not yet been clearly defined. We used

  6. Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling.

    Science.gov (United States)

    Arno, Anna I; Amini-Nik, Saeid; Blit, Patrick H; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine; Tien, Col Homer; Jeschke, Marc G

    2014-02-24

    The prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton's jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin. Human WJ-MSCs and normal skin fibroblasts were isolated from donated umbilical cords and normal adult human skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or nonconditioned medium. Expression of genes involved in re-epithelialization (transforming growth factor-β2), neovascularization (hypoxia-inducible factor-1α) and fibroproliferation (plasminogen activator inhibitor-1) was upregulated in WJ-MSC-CM-treated fibroblasts (P≤0.05). WJ-MSC-CM enhanced normal skin fibroblast proliferation (P≤0.001) and migration (P≤0.05), and promoted wound healing in an excisional full-thickness skin murine model. Under our experimental conditions, WJ-MSCs enhanced skin wound healing in an in vivo mouse model.

  7. DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

    Science.gov (United States)

    Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

    2015-01-01

    Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

  8. The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

    Directory of Open Access Journals (Sweden)

    Seim Inge

    2009-05-01

    Full Text Available Abstract Background The murine ghrelin gene (Ghrl, originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0. We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. Findings 5' RACE revealed two transcription start sites (TSSs in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR, we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. Conclusion We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1 raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.

  9. Metabolic shifts in the myocardium in the long-term effect of atmospheric pollution on the body

    Energy Technology Data Exchange (ETDEWEB)

    Tsapok, P I; Turdakin, P G; Barkov, L V; Ovcharuk, I N; Protod' iakonova, T N

    1981-04-01

    Metabolic shifts in the myocardium under conditions of long-term exposure of the body to air pollution were studied in experiments on albino rats. Study of the content of protein, RNA, DNA, glycogen, ATP, lactic and pyruvic acids and the activity of lactate dehydrogenase and creatine kinase in the heart muscle allowed the conclusion that the glycolytic processes are intensified, the bioenergic processes are inhibited and the synthesis of protein and RNA are increased in the myocardium of the experimental animals.

  10. Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

    Science.gov (United States)

    Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

    2016-04-15

    It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Age-dependent changes in expression of alpha1-adrenergic receptors in rat myocardium

    International Nuclear Information System (INIS)

    Schaffer, W.; Williams, R.S.

    1986-01-01

    The expression of alpha 1 -adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from [ 125 I] 2-(β hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha 1 -adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha 1 -adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha 1 -adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium

  12. Provocation of skin graft rejection across murine class II differences by non--bone-marrow-derived cells

    International Nuclear Information System (INIS)

    Stuart, P.M.; Beck-Maier, B.; Melvold, R.W.

    1984-01-01

    We have evaluated the relative contribution of bone-marrow-derived cells to skin allograft immunogenicity in mice differing only at class II major histocompatibility genes by using bone marrow radiation chimeras as donors. The mouse strains used were C57BL/6Kh (B6) and B6.C-H-2bm12 (bm12), which differ only at at A beta gene of the I region of the mouse H-2 complex. Our results demonstrated that skin from (B6----bm12) chimeras was accepted by bm12 recipients and rejected by B6 mice in a manner indistinguishable from that of normal bm12 skin. Likewise, naive bm12 mice rejected (bm12----B6) chimeric skin and normal B6 skin equally well, and B6 animals accepted both types of skin grafts. Our data argues that the donor cell-type leading to graft rejection across limited I region differences is not of bone marrow origin, and that these cells must--at least under certain circumstances--express class II antigens

  13. Importance of scintigraphy of the myocardium with Csup(99m)-Tc-pyrophosphate in the diagnosis of myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Botnar' , V I; Dvoskina, I S [Inst. Kardiologii Vsesoyuznogo Kardiologicheskogo Nauchnogo Tsentra AN SSSR

    1983-10-01

    The following aspects of the method of scintigraphy of the myocardium with sup(99m)Tc-pyrophosphate as test sensitivity, possibility of estimating necrosis focus, prognostic importance of the method, scintigram dynamics in case of acute infarction, pyrophosphate accumulation in myocardial cells are considered. Advantages and prospects of the method for visualization of acute myocardium infarction focus and in cases of other pathological states are pointed out.

  14. Delayed uptake and washout of contrast in non-viable infarcted myocardium shown with dynamic computed tomography

    DEFF Research Database (Denmark)

    Udholm, Sebastian; Laugesen, Sofie; Agger, Peter

    2014-01-01

    BACKGROUND: Assessment of ischemic but potentially viable myocardium plays an important role in the planning of coronary revascularization. Until now SPECT, PET, and MRI have been used to identify viable myocardium. Computed tomography (CT) is increasingly used to diagnose coronary atherosclerosis...... descending artery, followed by removal of the balloon and reperfusion. Four pigs died due to refractory ventricular fibrillation. After 6 weeks, dynamic cardiac CT was performed assessing both wall motion and contrast attenuation. Measurements of attenuation values in Hounsfield units (HU) in the infarct...

  15. Ecotropic murine leukemia virus-induced fusion of murine cells

    International Nuclear Information System (INIS)

    Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

    1986-01-01

    Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [ 3 H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells

  16. Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

    International Nuclear Information System (INIS)

    Webb, Meghan; Myal, Yvonne; Shiu, Robert; Murphy, Leigh C; Watson, Peter H; Emberley, Ethan D; Lizardo, Michael; Alowami, Salem; Qing, Gefei; Alfia'ar, Abdullah; Snell-Curtis, Linda J; Niu, Yulian; Civetta, Alberto

    2005-01-01

    The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression

  17. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    Science.gov (United States)

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

    2014-02-01

    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

  18. HPV16-E7-Specific Activated CD8 T Cells in E7 Transgenic Skin and Skin Grafts

    Directory of Open Access Journals (Sweden)

    Seyed Davoud Jazayeri

    2017-05-01

    Full Text Available Human papillomavirus (HPV 16 E7 (E7 protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA, with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin. To determine whether failure of rejection of E7 skin grafts is due to failure to attract E7-specific effector T cells, E7- and OVA-specific effector CD8+ T cells, activated in vitro, were transferred to animals bearing E7 transgenic skin grafts. Three days after T cell transfer, E7-specific T cells were present in significantly greater numbers than OVA-specific T cells in the grafted skin on animals bearing recently placed or healed E7 grafts, without graft rejection, and also in the ear skin of E7 transgenic animals, without obvious pathology. E7 and OVA-specific T cells were present in lesser numbers in healed E7 grafts than in recently placed grafts and in lesser numbers in recently placed E7 transgenic epidermal grafts without E7-associated hyperproliferation, derived from E7 transgenic mice with a mutated retinoblastoma gene. These data demonstrate that effector T cells are to some extent attracted to E7 transgenic skin specifically by E7 expression, but in large measure non-specifically by the epithelial proliferation associated with E7 expression, and by the local inflammation produced by grafting. Failure of E7 graft rejection was observed despite trafficking of E7-specific effector T cells to E7-expressing epithelium, a finding of consequence for immunotherapy of HPV 16 E7-associated human cancers.

  19. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  20. A Review of Neurogenic Stunned Myocardium

    Science.gov (United States)

    Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

    2017-01-01

    Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. PMID:28875040

  1. Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

    Directory of Open Access Journals (Sweden)

    Juan Carlos Chachques

    2011-01-01

    Full Text Available Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

  2. Kinetics of thallium-201 in reperfused canine myocardium after coronary artery occlusion

    International Nuclear Information System (INIS)

    Okada, R.D.

    1984-01-01

    To study the kinetics of thallium-201 in nonsalvaged acutely infarcted myocardium and salvaged myocardium, the tracer was administered after experimental left anterior descending coronary artery reperfusion 2 hours after occlusion. In 19 dogs, thallium activity was then monitored for 4 hours in the reperfused anterior wall and normal posterior wall using miniature cadmium telluride radiation detectors. After sacrifice, 13 of the dogs were found to have an infarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean (+/- standard deviation) fractional 4 hour thallium clearance was 0.33 +/- 0.08 for the infarct zone and 0.15 +/- 0.06 for the normal control zone (p less than 0.001). When computer-modeled, the clearance curve from the infarct zone was biexponential. The second exponential clearance curve from the infarct zone began 19.1 +/- 3.2 minutes after tracer administration, and was indistinguishable from the monoexponential clearance curve from the normal control zone. Thallium clearance from the blood pool was triexponential, the final exponential clearance curve being indistinguishable from the normal control zone clearance curve. Six dogs were found to have a salvaged noninfarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean fractional 4 hour thallium clearance was 0.20 +/- 0.07 for the reperfused zone, and 0.19 +/- 0.08 for the normal control zone (p . NS). When computer-modeled, clearance curves for the reperfused and control zones were monoexponential. The monoexponential clearance curve for the salvaged reperfused zone was indistinguishable from the monoexponential clearance curve for normal myocardium

  3. Immunomodulatory effects of balneotherapy with hae-un-dae thermal water on imiquimod-induced psoriasis-like murine model.

    Science.gov (United States)

    Lee, Young Bok; Lee, Jun Young; Lee, Hye Jin; Yun, Seong Taek; Lee, Jong Tae; Kim, Hong Jig; Yu, Dong Soo; Woo, So Youn; Kim, Jin-Wou

    2014-04-01

    Balneotherapy, although not a well-established dermatological treatment, is thought to have therapeutic properties for psoriasis and is used as an alternative treatment modality throughout the world. To evaluate the mechanism underlying the therapeutic immunologic effects of thermomineral water. A murine model of imiquimod-induced psoriasis-like skin inflammation was used for evaluating the therapeutic effects of balneotherapy with Hae-Un-Dae hot spring mineral water. The clinical improvements were evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A, IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase polymerase chain reaction. Serum levels of interferon-γ, IL-4, IL-5, and IL-17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the spleen were evaluated by flow cytometry, and histopathological evaluation of the skin was also performed. The mineral water balneotherapy group showed faster improvement in skin erythema and scales than the distilled water bathing group. A substantial reduction was observed in the lesional mRNA levels of IL-17A and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were significantly decreased in the mineral water group but not in the distilled water group. Normalized T cell proportions were observed after bathing. Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model. Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines in the pathogenesis of psoriasis. These results suggest that balneotherapy can be used as an effective and safe treatment for psoriasis.

  4. Improved identification of viable myocardium using second harmonic imaging during dobutamine stress echocardiography

    NARCIS (Netherlands)

    F. Sozzi (Fabiola); D. Poldermans (Don); J.J. Bax (Jeroen); A. Elhendy (Abdou); E.C. Vourvouri (Eleni); R. Valkema (Roelf); J. de Sutter; A.F.L. Schinkel (Arend); A. Borghetti; J.R.T.C. Roelandt (Jos)

    2001-01-01

    textabstractOBJECTIVE: To determine whether, compared with fundamental imaging, second harmonic imaging can improve the accuracy of dobutamine stress echocardiography for identifying viable myocardium, using nuclear imaging as a reference. PATIENTS: 30 patients with chronic left

  5. Statistical and fractal analysis of autofluorescent myocardium images in posthumous diagnostics of acute coronary insufficiency

    Science.gov (United States)

    Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Garazdiuk, M.; Motrich, A. V.

    2014-08-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  6. Manifestation of automaticity in the pulmonary-vein myocardium of rats with abdominal aorto-venocaval shunt

    Directory of Open Access Journals (Sweden)

    Shogo Hamaguchi

    2015-08-01

    Full Text Available Effect of abdominal aorto-venocaval shunt (AVS on the automaticity of the pulmonary-vein myocardium was studied in the rat. Spontaneous electrical activity was observed in one third of the isolated pulmonary-vein preparations from the AVS rats, but scarcely in those from sham-operated rats; the activity was induced by tertiapin and suppressed by carbachol or chelation of intracellular Ca2+. The evoked action potentials in AVS rats had less negative resting membrane potential and longer action potential duration than those in sham-operated rats. These results suggest that the automaticity of the rat pulmonary-vein myocardium is manifested under chronic volume overload.

  7. Multivariate Models for Prediction of Human Skin Sensitization Hazard

    Science.gov (United States)

    Strickland, Judy; Zang, Qingda; Paris, Michael; Lehmann, David M.; Allen, David; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Kleinstreuer, Nicole

    2016-01-01

    One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays—the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens™ assay—six physicochemical properties, and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches, logistic regression (LR) and support vector machine (SVM), to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three LR and three SVM) with the highest accuracy (92%) used: (1) DPRA, h-CLAT, and read-across; (2) DPRA, h-CLAT, read-across, and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens, and log P. The models performed better at predicting human skin sensitization hazard than the murine local lymph node assay (accuracy = 88%), any of the alternative methods alone (accuracy = 63–79%), or test batteries combining data from the individual methods (accuracy = 75%). These results suggest that computational methods are promising tools to effectively identify potential human skin sensitizers without animal testing. PMID:27480324

  8. Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    S. A. Afanasiev

    2016-01-01

    Full Text Available Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR with diabetes mellitus (DM animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes.

  9. Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Neese, R.A.; Araujo, L.

    1989-01-01

    Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis

  10. Observation of 99Tcm-MIBI uptake of ischemic myocardium in dog models after left circumflex coronary artery constriction

    International Nuclear Information System (INIS)

    Cheng Guanghua; Dai Yunhai; Wu Kefang; Xu Quanfeng

    2008-01-01

    Objective: To observe 99 Tc m -MIBI uptake of ischemic myocardium at different times (1h, 4h) in dog models after left circumflex coronary artery constriction. Methods: 12 dog models of coronary artery stenosis were prepared by left circumflex coronary ligation, and were given injection of 99 Tc m -MIBI at the dosage of 185 MBq (5 mCi). Six models were sacrificed at one hour and four hours after the injection respectively. Radio-uptake in about 100 mg myocardium from both ischemic and non-ischemic sites were measured with r-counter. Results: No significant differences were found between ratios of radioactive count of ischemic over normal myocardial tissues at 1h and 4h after injection of 99 Tc m -MIBI (0.726±0.054 and 0.673±0.080, respective, t=1.3452, P >0.05). Conclusion: The extension of post-injection time would not increase 99 Tc m -MIBI uptake in ischemic myocardium. (authors)

  11. Dynamic MRI of ferumoxide-labeled bone mesenchmal stem cells after transplantation in infarcted myocardium

    International Nuclear Information System (INIS)

    Liu Qiong; Zhao Shihua; Lu Minjie; Jiang Shiliang; Yan Chaowu; Zhang Yan; Meng Liang; Tang Yue; Meng Xianmin; Wei Yingjie; Wang Qingzhi

    2009-01-01

    Objective: To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods: Adult Chinese mini-pigs (n=6) were subjected to open-chest experimental MI operation. Their autogeneic bone marrow-derived mesenchymal stem cells (MSCs) was cultured and doubly labeled with ferumoxides and DAPI. On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed. Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test. Results: The labeling efficiency of ferumoxides and DAPI was 100%. On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)%. Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T 2 * images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92±7.76)%,t=1.65, P=0.1158] and the size [(0.56±0.24) cm 2 vs (0.52±0.25) cm 2 , t=0.39, P=0.7044] of the lesions showed no statistical difference between the peri-infarct zone and the normal myocardium. At 3 weeks after injection, the signal contrast

  12. The mechanical fingerprint of murine excisional wounds.

    Science.gov (United States)

    Pensalfini, Marco; Haertel, Eric; Hopf, Raoul; Wietecha, Mateusz; Werner, Sabine; Mazza, Edoardo

    2018-01-01

    A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue. Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy

  13. Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature

    International Nuclear Information System (INIS)

    Seemann, Ingar; Gabriels, Karen; Visser, Nils L.; Hoving, Saske; Poele, Johannes A. te; Pol, Jeffrey F.; Gijbels, Marion J.; Janssen, Ben J.; Leeuwen, Fijs W. van; Daemen, Mat J.; Heeneman, Sylvia; Stewart, Fiona A.

    2012-01-01

    Background: Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear. Methods: Single doses of 2, 8, or 16 Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60 weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage. Results: Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40 weeks after 2, 8, and 16 Gy. Cardiac blood volume was decreased at 20 and 60 weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40 weeks after 8 and 16 Gy. Microvascular density in the left ventricle was decreased at 40 and 60 weeks after 8 and 16 Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16 Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16 Gy), and amyloidosis (16 Gy). 16 Gy lead to sudden death between 30 and 40 weeks in 38% of mice. Conclusions: Irradiation with 2 and 8 Gy induced modest changes in murine cardiac function within 20 weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death.

  14. [The protective action of nimodipine on the ischemic myocardium].

    Science.gov (United States)

    Tsorin, I B; Kazanova, G V; Kirsanova, G Iu; Chirkova, E Iu; Chichkanov, G G

    1992-01-01

    The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation.

  15. Effects of acute and chronic uremia on active cation transport in rat myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  16. Development of an in vivo method for determining material properties of passive myocardium

    Directory of Open Access Journals (Sweden)

    Espen Remme

    2004-10-01

    Full Text Available Calculation of mechanical stresses and strains in the left ventricular (LV myocardium by the finite element (FE method relies on adequate knowledge of the material properties of myocardial tissue. In this paper we present a model-based estimation procedure to characterize the stress-strain relationship in passive LV myocardium. A 3D FE model of the LV myocardium was used, which included morphological fiber and sheet structure and a nonlinear orthotropic constitutive law with different stiffness in the fiber, sheet and sheet-normal directions. The estimation method was based on measured wall strains. We analyzed the method's ability to estimate the material parameters by generating a set of synthetic strain data by simulating the LV inflation phase with known material parameters. In this way we were able to verify the correctness of the solution and to analyze the effects of measurement and model error on the solution accuracy and stability. A sensitivity analysis was performed to investigate the observability of the material parameters and to determine which parameters to estimate. The results showed a high degree of coupling between the parameters governing the stiffness in each direction. Thus, only one parameter in each of the three directions was estimated. For the tested magnitudes of added noise and introduced model errors, the resulting estimated stress-strain characteristics in the fiber and sheet directions converged with good accuracy to the known relationship. The sheet-normal stress-strain relationship had a higher degree of uncertainty as more noise was added and model error was introduced.

  17. Prediction of Skin Sensitization with a Particle Swarm Optimized Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Chenzhong Cao

    2009-07-01

    Full Text Available Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT and murine local lymph node assay (LLNA are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the training and the test sets, respectively. For the GPMT data set, the classification accuracies are 91.80% and 90.32% for the training and the test sets, respectively. The classification performances were greatly improved compared to those reported in the literature, indicating that the support vector machine optimized by particle swarm in this paper is competent for the identification of skin sensitizers.

  18. Prediction of Skin Sensitization with a Particle Swarm Optimized Support Vector Machine

    Science.gov (United States)

    Yuan, Hua; Huang, Jianping; Cao, Chenzhong

    2009-01-01

    Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT) and murine local lymph node assay (LLNA) are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs) are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the training and the test sets, respectively. For the GPMT data set, the classification accuracies are 91.80% and 90.32% for the training and the test sets, respectively. The classification performances were greatly improved compared to those reported in the literature, indicating that the support vector machine optimized by particle swarm in this paper is competent for the identification of skin sensitizers. PMID:19742136

  19. Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium.

    Science.gov (United States)

    Elmadhun, Nassrene Y; Sabe, Ashraf A; Lassaletta, Antonio D; Chu, Louis M; Kondra, Katelyn; Sturek, Michael; Sellke, Frank W

    2014-09-01

    Impaired angiogenesis is a known consequence of metabolic syndrome (MetS); however, the mechanism is not fully understood. Recent studies have shown that the notch signaling pathway is an integral component of cardiac angiogenesis. We tested, in a clinically relevant swine model, the effects of MetS on notch and apoptosis signaling in chronically ischemic myocardium. Ossabaw swine were fed either a regular diet (control [CTL], n = 8) or a high-cholesterol diet (MetS, n = 8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, the wine underwent cardiac harvest of the ischemic myocardium. Downregulation of pro-angiogenesis proteins notch2, notch4, jagged2, angiopoietin 1, and endothelial nitric oxide synthase were found in the MetS group compared with the CTL group. Also, upregulation of pro-apoptosis protein caspase 8 and downregulation of anti-angiogenesis protein phosphorylated forkhead box transcription factor 03 and pro-survival proteins phosphorylated P38 and heat shock protein 90 were present in the MetS group. Cell death was increased in the MetS group compared with the CTL group. Both CTL and MetS groups had a similar arteriolar count and capillary density, and notch3 and jagged1 were both similarly concentrated in the smooth muscle wall. MetS in chronic myocardial ischemia significantly impairs notch signaling by downregulating notch receptors, ligands, and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling, and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, suggesting that inhibition of notch signaling might underlie the decreased angiogenesis in later stages of MetS. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  20. Evaluation of the effect of radiation levels and dose rates in irradiation of murine fibroblasts used as a feeder layer in the culture of human keratinocytes

    International Nuclear Information System (INIS)

    Yoshito, Daniele; Almeida, Tiago L.; Santin, Stefany Plumeri; Somessari, Elizabeth S.R.; Silveira, Carlos G. da; Mathor, Monica B.; Altran, Silvana C.; Isaac, Cesar

    2009-01-01

    In 1975, Rheinwald and Green published an effective methodology for obtaining and cultivating human keratinocytes. This methodology consisted of seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate of which is then controlled through the action of ionizing radiation. The presence of the feeder layer encourages the development of keratinocyte colonies and their propagation in similar cultures, becoming possible several clinical applications as skin substitutes or wound dressings in situations such as post burn extensive skin loss and other skin disorders. However, good development of these keratinocytes depends on a high quality feeder layer among other factors. In the present work, we evaluated the relationship between radiation levels and dose rates applied to fibroblasts used in construction of feeder layers and the radiation effect on keratinocytes colonies forming efficiency. Results indicate 3T3 lineage murine fibroblasts irradiated with doses varying between 60 and 100 Gy can be used as a feeder layer immediately after irradiation or storage of the irradiated cells in suspension at 4 g C for 24 hours with similar results. The exception is when the irradiation dose rate is 2.75 Gyh -1 ; in this case, results suggested that the fibroblasts should be used immediately after irradiation. (author)

  1. Volume of myocardium perfused by coronary artery branches as estimated from 3D micro-CT images of rat hearts

    Science.gov (United States)

    Lund, Patricia E.; Naessens, Lauren C.; Seaman, Catherine A.; Reyes, Denise A.; Ritman, Erik L.

    2000-04-01

    Average myocardial perfusion is remarkably consistent throughout the heart wall under resting conditions and the velocity of blood flow is fairly reproducible from artery to artery. Based on these observations, and the fact that flow through an artery is the product of arterial cross-sectional area and blood flow velocity, we would expect the volume of myocardium perfused to be proportional to the cross-sectional area of the coronary artery perfusing that volume of myocardium. This relationship has been confirmed by others in pigs, dogs and humans. To test the body size-dependence of this relationship we used the hearts from rats, 3 through 25 weeks of age. The coronary arteries were infused with radiopaque microfil polymer and the hearts scanned in a micro- CT scanner. Using these 3D images we measured the volume of myocardium and the arterial cross-sectional area of the artery that perfused that volume of myocardium. The average constant of proportionality was found to be 0.15 +/- 0.08 cm3/mm2. Our data showed no statistically different estimates of the constant of proportionality in the rat hearts of different ages nor between the left and right coronary arteries. This constant is smaller than that observed in large animals and humans, but this difference is consistent with the body mass-dependence on metabolic rate.

  2. Inflammatory Murine Skin Responses to UV-B Light Are Partially Dependent on Endothelin-1 and Mast Cells

    OpenAIRE

    Metz, Martin; Lammel, Verena; Gibbs, Bernhard F.; Maurer, Marcus

    2006-01-01

    Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assesse...

  3. Efficacy of Astaxanthin for the Treatment of Atopic Dermatitis in a Murine Model.

    Directory of Open Access Journals (Sweden)

    Yoko Yoshihisa

    Full Text Available Atopic dermatitis (AD is a common chronic inflammatory skin disease associated with various factors, including immunological abnormalities and exposure to allergens. Astaxanthin (AST is a xanthophyll carotenoid that has recently been demonstrated to have anti-inflammatory effects and to regulate the expression of inflammatory cytokines. Thus, we investigated whether AST could improve the dermatitis and pruritus in a murine model of AD using NC/Nga mice. In addition to a behavioral evaluation, the effects of AST on the AD were determined by the clinical skin severity score, serum IgE level, histological analyses of skin, and by reverse transcription-PCR and Western blotting analyses for the expression of inflammation-related factors. AST (100 mg/kg or vehicle (olive oil was orally administered once day and three times a week for 26 days. When compared with vehicle-treated group, the administration of AST significantly reduced the clinical skin severity score. In addition, the spontaneous scratching in AD model mice was reduced by AST administration. Moreover, the serum IgE level was markedly decreased by the oral administration of AST compared to that in vehicle-treated mice. The number of eosinophils, total and degranulated mast cells all significantly decreased in the skin of AST-treated mice compared with vehicle-treated mice. The mRNA and protein levels of eotaxin, MIF, IL-4, IL-5 and L-histidine decarboxylase were significantly decreased in the skin of AST-treated mice compared with vehicle-treated mice. These results suggest that AST improves the dermatitis and pruritus in AD via the regulation of the inflammatory effects and the expression of inflammatory cytokines.

  4. Detection of hibernating myocardium in patients with myocardial infarction by low-dose dobutamine echocardiography. Comparison with thallium-201 scintigraphy with reinjection

    International Nuclear Information System (INIS)

    Takagi, Tsutomu; Yoshikawa, Junichi; Yoshida, Kiyoshi; Akasaka, Takashi; Honda, Yasuhiro; Yonezawa, Yoshihiro; Shakudo, Masahiro

    1995-01-01

    The identification of hibernating myocardium is important for selecting patients who will benefit from coronary revascularization. The relationship between echocardiographic and radioisotopic markers of hibernating myocardium and postrevascularization recovery of myocardial function was investigated in 21 patients who underwent successful revascularization. Each patient underwent low-dose dobutamine stress echocardiography and thallium-201 ( 201 Tl) scintigraphy with reinjection before revascularization. The presence of contractile reserve in dobutamine stress echocardiography and Tl uptake in 201 Tl scintigraphy with reinjection were defined as markers of hibernating myocardium. Follow-up echocardiograms were evaluated for improved regional wall motion in all patients at a mean of 8.6 months after revascularization. Sensitivity, specificity, and positive and negative predictive values of low-dose dobutamine stress echocardiography for indicating recovery of function after revascularization were 75.0%, 77.8%, 81.8%, and 70.0%, respectively. Sensitivity, specificity, and positive and negative predictive values of 201 Tl scintigraphy with reinjection for indicating recovery of function after revascularization were 91.7%, 55.6%, 73.3%, and 83.3%, respectively. There were no statistical differences between low-dose dobutamine echocardiography and 201 Tl scintigraphy in predicting postrevascularization recovery of function in patients with hibernating myocardium. (author)

  5. Hepatic Mitochondrial Dysfunction and Immune Response in a Murine Model of Peanut Allergy

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    Giovanna Trinchese

    2018-06-01

    Full Text Available Background: Evidence suggests a relevant role for liver and mitochondrial dysfunction in allergic disease. However, the role of hepatic mitochondrial function in food allergy is largely unknown. We aimed to investigate hepatic mitochondrial dysfunction in a murine model of peanut allergy. Methods: Three-week-old C3H/HeOuJ mice were sensitized by the oral route with peanut-extract (PNT. We investigated: 1. the occurrence of effective sensitization to PNT by analysing acute allergic skin response, anaphylactic symptoms score, body temperature, serum mucosal mast cell protease-1 (mMCP-1 and anti-PNT immunoglobulin E (IgE levels; 2. hepatic involvement by analysing interleukin (IL-4, IL-5, IL-13, IL-10 and IFN-γ mRNA expression; 3. hepatic mitochondrial oxidation rates and efficiency by polarography, and hydrogen peroxide (H2O2 yield, aconitase and superoxide dysmutase activities by spectrophotometry. Results: Sensitization to PNT was demonstrated by acute allergic skin response, anaphylactic symptoms score, body temperature decrease, serum mMCP-1 and anti-peanut IgE levels. Liver involvement was demonstrated by a significant increase of hepatic Th2 cytokines (IL-4, IL-5 and IL-13 mRNA expression. Mitochondrial dysfunction was demonstrated by lower state 3 respiration rate in the presence of succinate, decreased fatty acid oxidation in the presence of palmitoyl-carnitine, increased yield of ROS proven by the inactivation of aconitase enzyme and higher H2O2 mitochondrial release. Conclusions: We provide evidence of hepatic mitochondrial dysfunction in a murine model of peanut allergy. These data could open the way to the identification of new mitochondrial targets for innovative preventive and therapeutic strategies against food allergy.

  6. Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling.

    Science.gov (United States)

    Feng, Jianhua; Fischer, Gregor; Lucchinetti, Eliana; Zhu, Min; Bestmann, Lukas; Jegger, David; Arras, Margarete; Pasch, Thomas; Perriard, Jean-Claude; Schaub, Marcus C; Zaugg, Michael

    2006-05-01

    Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium. Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion. Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase. Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.

  7. Appearance of high signal intensity and gadolinium-DTPA contrast enhancement in hypertrophied myocardium by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Yamada, Naoaki; Nagata, Seiki

    1989-01-01

    This study was undertaken to examine the potential role of magnetic resonance imaging (MRI) for evaluating myocardial tissue characterization in hypertrophic cardiomyopathy (HCM). ECG-gated MRI images were acquired in 32 HCM patients and 30 patients with hypertensive heart disease (HHD), using a 1.5 T superconducting magnet system. The thickened areas were depicted as high signal intensities in the septum of 12 HCM patients (38%) and the endocardium of 5 HHD patients (17%). Echocardiography revealed that MRI appearance of high signal intensity was associated with more thickened myocardial wall. For evaluable 16 patients receiving i.v. injection of Gd-DTPA in a dose of 0.1 mM/kg, enhancement effects were observed in 10 patients (63%). High signal intensity appearing in the hypertrophied myocardium, as well as contrast enhancement, may not be characteristic of HCM, but reflect the likelihood of myocardial degeneration associated with the hypertrophied myocardium. Although MRI may not be capable of differentiating tissue characterization in HCM from that in HHD, it may provide different information about tissue characterization in the hypertrophied myocardium from that obtained by other techniques. (N.K.)

  8. Immune sensitization to methylene diphenyl diisocyanate (MDI resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

    Directory of Open Access Journals (Sweden)

    Redlich Carrie A

    2011-03-01

    Full Text Available Abstract Background Methylene diphenyl diisocyanate (MDI, a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA, while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL. Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary respiratory tract inflammation and eosinophilia depended upon the (primary skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI. The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma

  9. Recommendations to realise and interpret the scintigraphy of myocardium perfusion

    International Nuclear Information System (INIS)

    Manrique, A.; Marie, P.Y.

    2003-06-01

    The purpose of these recommendations is to help the physicians in the realization and the interpretation of the tomo-scintigraphies of myocardium perfusion, when this examination is made at the patients having a known or suspected coronary incapacity. These recommendations aim to encourage the practitioners (of nuclear medicine) to reflect and to discuss the procedures applied in their services. These procedures must be also adapted, in every service, to the peculiarities of the environment and to the experiment of each one. (N.C.)

  10. In vivo evaluation of wound bed reaction and graft performance after cold skin graft storage: new targets for skin tissue engineering.

    Science.gov (United States)

    Knapik, Alicia; Kornmann, Kai; Kerl, Katrin; Calcagni, Maurizio; Schmidt, Christian A; Vollmar, Brigitte; Giovanoli, Pietro; Lindenblatt, Nicole

    2014-01-01

    Surplus harvested skin grafts are routinely stored at 4 to 6°C in saline for several days in plastic surgery. The purpose of this study was to evaluate the influence of storage on human skin graft performance in an in vivo intravital microscopic setting after transplantation. Freshly harvested human full-thickness skin grafts and split-thickness skin grafts (STSGs) after storage of 0, 3, or 7 days in moist saline at 4 to 6°C were transplanted into the modified dorsal skinfold chamber, and intravital microscopy was performed to evaluate vessel morphology and angiogenic change of the wound bed. The chamber tissue was harvested 10 days after transplantation for evaluation of tissue integrity and inflammation (hematoxylin and eosin) as well as for immunohistochemistry (human CD31, murine CD31, Ki67, Tdt-mediated dUTP-biotin nick-end labelling). Intravital microscopy results showed no differences in the host angiogenic response between fresh and preserved grafts. However, STSGs and full-thickness skin grafts exhibited a trend toward different timing and strength in capillary widening and capillary bud formation. Preservation had no influence on graft quality before transplantation, but fresh STSGs showed better quality 10 days after transplantation than 7-day preserved grafts. Proliferation and apoptosis as well as host capillary in-growth and graft capillary degeneration were equal in all groups. These results indicate that cells may activate protective mechanisms under cold conditions, allowing them to maintain function and morphology. However, rewarming may disclose underlying tissue damage. These findings could be translated to a new approach for the design of full-thickness skin substitutes.

  11. The development of a murine model for Forcipomyia taiwana (biting midge) allergy.

    Science.gov (United States)

    Lee, Mey-Fann; Yang, Kai-Jei; Wang, Nancy M; Chiu, Yung-Tsung; Chen, Pei-Chih; Chen, Yi-Hsing

    2014-01-01

    Forcipomyia taiwana (biting midge) allergy is the most prevalent biting insect allergy in Taiwan. An animal model corresponding to the human immuno-pathologic features of midge allergy is needed for investigating the mechanisms and therapies. This study successfully developed a murine model of Forcipomyia taiwana allergy. BALB/c mice were sensitized intra-peritoneally with midge extract on days 0, 7, 14, 21 then intra-dermally on days 28, 31 and 35. Serum midge-specific IgE, IgG1, and IgG2a were measured every 14 days by indirect ELISA. The mice were challenged intradermally with midge extract at day 40 and then sacrificed. Proliferation and cytokine production of splenocytes after stimulation with midge extract were determined by MTT assay and ELISA, respectively. The cytokine mRNA expression in response to midge stimulation was analyzed by RT-PCR. Serum IgE, total IgG, and IgG1 antibody levels against midge extract were significantly higher in the midge-sensitized mice than in the control mice. After the two-step sensitization, all mice in the midge-sensitized group displayed immediate itch and plasma extravasation reactions in response to challenge with midge extract. Skin histology from midge-sensitized mice showed marked eosinophil and lymphocyte infiltrations similar to that observed in humans. Stimulation of murine splenocytes with midge extract elicited significant proliferation, IL-4, IL-10, IL-13 and IFN-γ protein production, and up-regulation of mRNA in a dose-dependent manner in the midge-sensitized group, but not in the control group. A murine model of midge bite allergy has been successfully developed using a two-step sensitization protocol. The sensitized mice have very similar clinical and immunologic reactions to challenge with midge proteins as the reactions of human to midge bites. This murine model may be a useful platform for future research and the development of treatment strategies for insect bite allergy.

  12. Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice.

    Science.gov (United States)

    Man, Mao-Qiang; Sun, Richard; Man, George; Lee, Dale; Hill, Zelee; Elias, Peter M

    2016-09-01

    Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants. © 2016 Wiley Periodicals, Inc.

  13. Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation

    International Nuclear Information System (INIS)

    Murphree, S.S.; Saffitz, J.E.

    1989-01-01

    The density of beta-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [125Iodo]cyanopindolol to transmural slices of human myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of beta-receptors in failing myocardium (38.3 +/- 2.0 fmol/mg protein) compared with normal tissue (52.4 +/- 1.7 fmol/mg protein, p = 0.038). In the normal ventricles, the greatest receptor density was observed autoradiographically in myocytic regions of the subendocardium. Receptor density of the coronary arterioles was approximately 70% of that in adjacent myocytic regions. The density of binding sites in both myocytic regions and arterioles was diminished in all regions of the failing ventricles, but down-regulation was due primarily to a selective reduction of beta-receptors of subendocardial myocytes (63 +/- 5% of subepicardial receptor density vs. 115 +/- 6% in controls, p less than 0.0001). These observations indicate that down-regulation occurs nonuniformly in the transmural distribution and thus is likely not related simply to elevated circulating catecholamine levels

  14. Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models.

    Science.gov (United States)

    Brauchle, Eva; Bauer, Hannah; Fernes, Patrick; Zuk, Alexandra; Schenke-Layland, Katja; Sengle, Gerhard

    2017-04-01

    Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBN1) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1 GT8/GT8 fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease

  15. Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model.

    Directory of Open Access Journals (Sweden)

    Florian Marquet

    Full Text Available Transcutaneous delivery of vaccines to specific skin dendritic cells (DC subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC and dermal DC (DDC that could be divided in 3 subsets according to their phenotypes: (1 the CD163(neg/CD172a(neg, (2 the CD163(highCD172a(pos and (3 the CD163(lowCD172a(pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(negCD172(low DDC share properties with the CD8(+ T cell response-inducing murine skin CD103(pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

  16. Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent.

    Science.gov (United States)

    von Lewinski, Dirk; Stumme, Burkhard; Maier, Lars S; Luers, Claus; Bers, Donald M; Pieske, Burkert

    2003-03-15

    Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium. Experiments were performed in isolated right ventricular muscles from adult rabbit hearts (37 degrees C, 1 Hz stimulation rate, bicarbonate-buffer). Muscles were rapidly stretched from 88% of optimal length (L88) to near optimal length (L98) for functional analysis. The resulting immediate and slow increases in twitch force (first phase and SFR, respectively) were assessed at reduced [Na+]o or without and with blockade of stretch activated ion channels (SACs), angiotensin-II (AT1) receptors, endothelin-A (ET(A)) receptors, Na+/H+-exchange (NHE1), reverse mode Na+/Ca2+-exchange (NCX), or Na+/K+-ATPase. The effects of stretch on sarcoplasmic reticulum Ca2+-load were characterized using rapid cooling contractures (RCCs). Intracellular pH was measured in BCECF-AM loaded muscles, and action potential duration (APD) was assessed using floating electrodes. On average, force increased to 216+/-8% of the pre-stretch value during the immediate phase, followed by a further increase to 273+/-10% during the SFR (n=81). RCCs significantly increased during SFR, whereas pH and APD did not change. Neither inhibition of SACs, AT1, or ET(A) receptors affected the stretch-dependent immediate phase nor SFR. In contrast, SFR was reduced by NHE inhibition and almost completely abolished by reduced [Na+]o or inhibition of reverse-mode NCX, whereas increased SFR was seen after raising [Na+]i by Na+/K+-ATPase inhibition. The data demonstrate the existence of a delayed, Na+- and Ca2+-dependent but pH and APD independent SFR to stretch in rabbit myocardium. This inotropic response appears to be independent of autocrine/paracrine AT1 or ET(A) receptor activation, but mediated through stretch-induced activation of NHE and reverse mode NCX.

  17. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  18. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    NARCIS (Netherlands)

    X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised

  19. Neurogenic stunned myocardium following hemorrhagic cerebral contusion

    International Nuclear Information System (INIS)

    Deleu, D.; Miyares, F.; Kettern, M.; Kumar, S.; Hassens, Y.; Salim, K.

    2007-01-01

    Neurogenic stunned myocardium NSM is a well-known complication of subarachnoidal hemorrhage, but has been reported rarely in association with other central nervous system disorders. A case of NSM is described in a patient with hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man was admitted with severe cranial trauma following a car roll-over. Six days after admission, he developed findings suggestive for NSM. The troponin T and creatine kinase-MB level were elevated and echocardiogram showed apical and inferoposterior hypokinesis and diffuse left ventricular akinesis with severely reduced ejection fraction 18%. Invasive measurements confirmed low cardiac output. His cardiac function resolved completely within 6 days after decompressive craniotomy. This case supports the presumed unifying role of the increased intracranial pressure, probably triggering a vigorous sympathetic outflow hyperactivity leading to NSM. (author)

  20. Epidermal changes following application of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate to human skin transplanted to nude mice studied with histological species markers

    International Nuclear Information System (INIS)

    Graem, N.

    1986-01-01

    Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue

  1. Reexamination of the role of Lyt-2-positive T cells in murine skin graft rejection

    International Nuclear Information System (INIS)

    LeFrancois, L.; Bevan, M.J.

    1984-01-01

    The authors have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. The authors found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process

  2. Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

    International Nuclear Information System (INIS)

    Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B.; Altran, Silvana C.; Isaac, Cesar

    2011-01-01

    Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

  3. Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Altran, Silvana C.; Isaac, Cesar [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Lab. de Microcirurgia Plastica; Esteves-Pedro, Natalia M. [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Ciencias Farmaceuticas. Lab. de Controle Biologico; Herson, Marisa R. [DonorTissue Bank of Victoria (Australia)

    2011-07-01

    Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

  4. Reductions in mitochondrial O(2) consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium.

    Science.gov (United States)

    Hu, Qingsong; Suzuki, Gen; Young, Rebeccah F; Page, Brian J; Fallavollita, James A; Canty, John M

    2009-07-01

    We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 +/- 0.2 vs. 5.4 +/- 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37 degrees C). At baseline, ATP (20.1 +/- 1.0 vs. 26.7 +/- 2.1 micromol/g dry wt, P < 0.05), ADP (8.1 +/- 0.4 vs. 10.3 +/- 0.8 micromol/g, P < 0.05), and total adenine nucleotides (31.2 +/- 1.3 vs. 40.1 +/- 2.9 micromol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 +/- 0.9 vs. 13.7 +/- 1.7 micromol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 +/- 13 vs. 187 +/- 11 ng atoms O(2).mg protein(-1).min(-1) in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

  5. Detection of viable myocardium in canine model with myocardial ischemia and ischemia-reperfusion by 125I-BMIPP: relation to regional blood flow

    International Nuclear Information System (INIS)

    Huang Gang; Zhao Huiyang; Shen Xuedong; Li Qing; Yuan Jimin; Zhu Cuiying

    1999-01-01

    Objective: The effects of BMIPP (β-methyl-iodophenyl pentadecanoic acid) on detecting viable myocardium and the relation between regional blood flow and the uptake of BMIPP were evaluated in canine model of myocardial ischemia and ischemia-reperfusion. Methods: 12 open-chest dogs under anesthesia were divided into two groups. Group I (ischemia group) had left circumflex coronary arterial occlusion for 2 h and group II (ischemia-reperfusion group) was occluded for 1 h and followed by 2 h reperfusion. Myocardial blood flow was measured with 99 Tc m -microspheres. 30 min after intravenous injection of 125 I-BMIPP and 99 Tc m -microspheres, the heart was excised rapidly and stained with Evans blue and NBT. Tissue samples (divided into approximately 1 g) of left ventricle were obtained, weighed and counted for 125 I and 99 Tc m . Regional blood flow and the uptake of BMIPP were expressed as percentages of average values in non-ischemic myocardium (two to three tissue samples) from the normal myocardium. Results: In ischemic myocardium (NBT positive samples), the uptake of BMIPP was relatively higher compared with regional blood flow [(67 +- 23)% vs (42 +- 19)%, P 0.05]. In ischemia-reperfusion group, regional blood flow was increased in ischemic and necrotic tissues, but the uptake of BMIPP was not enhanced with the increasing blood flow. Conclusions: BMIPP uptake seems to provide metabolic information independent of regional blood flow. The mismatching between regional blood flow and BMIPP uptake may indicate myocardial viability in the regions of hypoperfusion and the uptake of BMIPP in ischemic myocardium was related to existence of cellular metabolism

  6. Quantitative Differentiation of LV Myocardium with and without Layer-Specific Fibrosis Using MRI in Hypertrophic Cardiomyopathy and Layer-Specific Strain TTE Analysis.

    Science.gov (United States)

    Funabashi, Nobusada; Takaoka, Hiroyuki; Ozawa, Koya; Kamata, Tomoko; Uehara, Masae; Komuro, Issei; Kobayashi, Yoshio

    2018-05-30

    To achieve further risk stratification in hypertrophic cardiomyopathy (HCM) patients, we localized and quantified layer-specific LVM fibrosis on MRI in HCM patients using regional layer-specific peak longitudinal strain (PLS) and peak circumferential strain (PCS) in LV myocardium (LVM) on speckle tracking transthoracic echocardiography (TTE). A total of 18 HCM patients (14 males; 58 ± 17 years) underwent 1.5T-MRI and TTE. PLS and PCS in each layer of the LVM (endocardium, epicardium, and whole-layer myocardium) were calculated for 17 AHA-defined lesions. MRI assessment showed that fibrosis was classified as endocardial, epicardial, or whole-layer (= either or both of these). Regional PLS was smaller in fibrotic endocardial lesions than in non-fibrotic endocardial lesions (P = 0.004). To detect LV endocardial lesions with fibrosis, ROC curves of regional PLS revealed an area under the curve (AUC) of 0.609 and a best cut-off point of 13.5%, with sensitivity of 65.3% and specificity of 54.3%. Regional PLS was also smaller in fibrotic epicardial lesions than in non-fibrotic epicardial lesions (P layer myocardium analysis, PLS was smaller in fibrotic lesions than in non-fibrotic lesions (P layer LV lesions with fibrosis, ROC curves of regional PLS revealed an AUC of 0.674 and a best cut-off point of 12.5%, with sensitivity of 79.0% and specificity of 50.7%. There were no significant differences in PCS of LV myocardium (endocardium, epicardium, and whole-layer) between fibrotic and non-fibrotic lesions. Quantitative regional PLS but not PCS in LV endocardium, epicardium, and whole-layer myocardium provides useful non-invasive information for layer-specific localization of fibrosis in HCM patients.

  7. RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Anxin Gu

    Full Text Available Radiation-induced heart disease (RIHD, which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

  8. Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum. An X-ray diffraction study

    International Nuclear Information System (INIS)

    White, S.H.; Mirejovsky, D.; King, G.I.

    1988-01-01

    The lipid of the outermost layer of the skin is confined largely to the extracellular spaces surrounding the corneocytes of the stratum corneum where it forms a multilamellar adhesive matrix to act as the major permeability barrier of the skin. Knowledge of the molecular architecture of these intercellular domains is important for understanding various skin pathologies and their treatment, percutaneous drug delivery, and the cosmetic maintenance of the skin. The authors have surveyed by X-ray diffraction the structure of the intercellular domains and the extracted lipids of murine stratum corneum (SC) at 25, 45, and 70 0 C which are temperatures in the vicinity of known thermal phase transitions. The intercellular domains produce lamellar diffraction patterns with a Bragg spacing of 131 +/- 2 A. Lipid extracted from the SC and dispersed in excess water does not produce a simple lamellar diffraction pattern at any temperature studied, however. This and other facts suggest that another component, probably a protein, must be present to control the architecture of the intercellular lipid domains. They have also obtained diffraction patterns attributable to the protein envelopes of the corneocytes. The patterns suggest a β-pleated sheet organizational scheme. No diffraction patterns were observed that could be attributed to keratin

  9. Imported rickettsioses : think of murine typhus

    NARCIS (Netherlands)

    van der Kleij, FGH; Gansevoort, RT; Kreeftenberg, HG

    Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur,

  10. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

    Directory of Open Access Journals (Sweden)

    Alexis Dumortier

    2010-02-01

    Full Text Available The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD, characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP, a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia.Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

  11. Non-animal methods to predict skin sensitization (II): an assessment of defined approaches *.

    Science.gov (United States)

    Kleinstreuer, Nicole C; Hoffmann, Sebastian; Alépée, Nathalie; Allen, David; Ashikaga, Takao; Casey, Warren; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Göbel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Strickland, Judy; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

    2018-05-01

    Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.

  12. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions

    DEFF Research Database (Denmark)

    Zibert, John Robert; Wallbrecht, Katrin; Schön, Margarete

    2011-01-01

    Dysregulated angiogenesis is a hallmark of chronic inflammatory diseases, including psoriasis, a common skin disorder that affects approximately 2% of the population. Studying both human psoriasis in 2 complementary xenotransplantation models and psoriasis-like skin lesions in transgenic mice......-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models. As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue....... High-resolution ultrasound revealed reduced cutaneous blood flow in vivo after electroporation with RDD but not with control plasmids. In addition, angiogenesis- and inflammation-related molecular markers, keratinocyte proliferation, epidermal thickness, and clinical disease scores were downregulated...

  13. Study of shape memory alloy fibers for the development of artificial myocardium.

    Science.gov (United States)

    Hassoulas, Ioannis A; Ladopoulos, Vlassios S; Kalogerakos, Paris-Dimitrios K

    2010-01-01

    Circulatory support devices are employed to treat heart failure. Such a device could be made from shape memory alloy (SMA) fibers. These Ni-Ti fibers contract when electric current flows through them, thus resembling artificial muscles. An artificial myocardium device made from SMA fibers can directly compress the epicardial surface of a failing heart, thus contributing to the pumping action. Unlike modern mechanical circulatory support devices, there is no blood-contacting surface to provoke thromboembolism, hemorrhage, inflammatory response or hemolysis. The experimental setup permitted a detailed study of a sample SMA fiber with great accuracy while the ambient temperature was controlled to resemble that of the human body. The current profile through the fiber was controlled (current shaping, CS) by a microcontroller and a portable computer. Parameters such as strain, contraction and relaxation velocities and the effect of ambient temperature were measured. The contraction and relaxation velocities were measured after applying various effective currents. It was found that the contraction velocity could be manipulated to reach that of the healthy myocardium through CS. On the other hand, the relaxation velocity was independent of the contraction velocity. A cardiac assist device can be made from SMA fibers. More studies need to be conducted in this direction.

  14. The Standardized Extract of Juniperus communis Alleviates Hyperpigmentation in Vivo HRM-2 Hairless Mice and in Vitro Murine B16 Melanoma Cells.

    Science.gov (United States)

    Jegal, Jonghwan; Chung, Ki Wung; Chung, Hae Young; Jeong, Eun Ju; Yang, Min Hye

    2017-01-01

    In European folk medicine, the fruits of Juniperus communis are used in the treatment of skin-related disorders such as skin infection, itching, and psoriasis. Previously, we reported that the EtOAc fraction of J. communis (EAJC) contained tyrosinase inhibition properties in vitro non-cellular experiment. The aim of this study was to evaluate anti-melanogenic effect of standardized EAJC on a hyperpigmentation animal model. Therapeutic effects of EAJC toward skin hyperpigmentation were confirmed by both in vivo experiment and in vitro cell-based assay. Skin depigmenting effect was detected by topical treatment of EAJC for 11 d to HRM-2 melanin-possessing hairless mice. Histologic findings including significantly decreased melanin depositions could be observed in dorsal skin samples of EAJC-treated group. In addition, the EAJC (50 µg/mL) attenuated melanin production through down-regulation of tyrosinase activity and protein expression in B16 murine melanoma cells. According to the phytochemical analysis, EAJC was found to contain hypolaetin-7-O-β-D-xylopyranoside and isoscutellarein-7-O-β-D-xylopyranoside as main components. Hypolaetin-7-O-β-D-xylopyranoside was responsible for the skin-lightening effect of EAJC by reducing the number of melanocytes in dorsal skins of HRM-2 mice. The present study provided direct experimental evidence for skin-lightening effect of EAJC in UV-irradiated hairless mouse model. Therapeutic attempts with the J. communis might be useful in the management of skin pigmentation-related diseases.

  15. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

    2013-04-01

    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p MFRs (r =-0.424, p MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  16. QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

    Science.gov (United States)

    Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2016-01-01

    Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for virtual screening of CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternative to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. PMID:28630595

  17. Relationship between iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid washout ratio and oxygen consumption in normal and ischemic myocardium

    International Nuclear Information System (INIS)

    Saito, Kimimasa; Okamoto, Ryuji; Saito, Yasuhiro

    1997-01-01

    The relationship between oxygen consumption and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid ( 123 I-BMIPP) washout at rest and after exercise was investigated in normal and ischemic myocardium. Sixteen healthy volunteers and 14 patients with ischemic heart disease were examined. After injection of 111 MBq of 123 I-BMIPP, serial single photon emission computed tomography imaging was performed to evaluate washout ratio after 30 min and 1 hour of rest and after exercise. In the volunteers, the mean washout ratio was 3.3±3.5% after 1 hour of rest and increased during exercise. The exercise washout ratio showed a better correlation with net pressure rate product (net PRP: cumulative values of PRP during exercise) than with the peak PRP. The exercise washout ratio showed a strong correlation with the net PRP in the range from 180 to 300x10 3 mmHg·beat/min and a plateau of 10-15%. In the nine ischemic patients with net PRP≥300x10 3 mmHg·beat/min, the exercise washout ratio values were significantly elevated in normal segments relative to ischemic segments (10.1±1.9% vs 4.7±2.9%, p 3 mmHg·beat/min, washout ratio at rest and after exercise did not differ significantly between normal and ischemic segments. 123 I-BMIPP washout ratio increased with increased oxygen consumption during exercise in normal myocardium but not in ischemic myocardium. The patient must exercise before fatty acid metabolism can be compared between normal and ischemic myocardium. (author)

  18. Segmenting high-frequency intracardiac ultrasound images of myocardium into infarcted, ischemic, and normal regions.

    Science.gov (United States)

    Hao, X; Bruce, C J; Pislaru, C; Greenleaf, J F

    2001-12-01

    Segmenting abnormal from normal myocardium using high-frequency intracardiac echocardiography (ICE) images presents new challenges for image processing. Gray-level intensity and texture features of ICE images of myocardium with the same structural/perfusion properties differ. This significant limitation conflicts with the fundamental assumption on which existing segmentation techniques are based. This paper describes a new seeded region growing method to overcome the limitations of the existing segmentation techniques. Three criteria are used for region growing control: 1) Each pixel is merged into the globally closest region in the multifeature space. 2) "Geographic similarity" is introduced to overcome the problem that myocardial tissue, despite having the same property (i.e., perfusion status), may be segmented into several different regions using existing segmentation methods. 3) "Equal opportunity competence" criterion is employed making results independent of processing order. This novel segmentation method is applied to in vivo intracardiac ultrasound images using pathology as the reference method for the ground truth. The corresponding results demonstrate that this method is reliable and effective.

  19. Bee Venom Phospholipase A2 Alleviate House Dust Mite-Induced Atopic Dermatitis-Like Skin Lesions by the CD206 Mannose Receptor.

    Science.gov (United States)

    Shin, Dasom; Choi, Won; Bae, Hyunsu

    2018-04-02

    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic, erythematous, and eczematous skin plaques. We previously reported that phospholipase A2 (PLA2) derived from bee venom alleviates AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite extract ( Dermatophagoides farinae extract, DFE) in a murine model. However, the underlying mechanisms of PLA2 action in actopic dermatitis remain unclear. In this study, we showed that PLA2 treatment inhibited epidermal thickness, serum immunoglobulin E (IgE) and cytokine levels, macrophage and mast cell infiltration in the ear of an AD model induced by DFE and DNCB. In contrast, these effects were abrogated in CD206 mannose receptor-deficient mice exposed to DFE and DNCB in the ear. These data suggest that bvPLA2 alleviates atopic skin inflammation via interaction with CD206.

  20. Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium

    Czech Academy of Sciences Publication Activity Database

    Ammirabile, G.; Tessari, A.; Pignataro, V.; Szumska, D.; Sardo, F.S.; Beneš Jr., Jiří; Balistreri, M.; Bhattacharya, S.; Sedmera, David; Campione, M.

    2012-01-01

    Roč. 93, č. 2 (2012), s. 291-301 ISSN 0008-6363 R&D Projects: GA ČR(CZ) GA304/08/0615 Institutional research plan: CEZ:AV0Z50110509 Keywords : Pitx2 * sinus venosus myocardium * optical mapping * mouse cardiac development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.940, year: 2012

  1. 19-DEJ-1, a hemidesmosome-anchoring filament complex-associated monoclonal antibody. Definition of a new skin basement membrane antigenic defect in junctional and dystrophic epidermolysis bullosa

    DEFF Research Database (Denmark)

    Fine, J D; Horiguchi, Y; Couchman, J R

    1989-01-01

    A murine monoclonal antibody (19-DEJ-1) was recently produced that recognizes a unique antigenic epitope of human skin basement membrane localized to the midlamina lucida exclusively in those areas bordered by overlying hemidesmosomes. To determine whether the antigen defined by 19-DEJ-1 is norma...

  2. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    International Nuclear Information System (INIS)

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-01-01

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

  3. Irradiated murine fibroblasts as feeder layer used in human cell culture

    International Nuclear Information System (INIS)

    Almeida, Tiago L.; Klingbeil, Fatima G.; Yoshito, Daniele; Caproni, Priscila; Mathor, Monica B.; Herson, Marisa R.

    2007-01-01

    In 1975, Rheinwald and Green published an in vitro model for keratinocyte cell cultures in which the use of murine fibroblasts, as a feeder layer was introduced. These cells are modified fibroblasts, which presence render keratinocyte cells to remain proliferative for longer periods of time. This optimization of culture outputs has allowed for several clinical applications of confluent keratinocyte cultures as skin substitutes or wound dressings in situations such as post burn extensive skin loss, loss of oral mucosa, and other skin disorders. Nevertheless, proliferation of fibroblast in co-culture with keratinocytes must be controlled by anti-proliferative measures such as irradiation; at the same time, keratinocytes require specific nutrients in the culture medium, which may interfere with the fibroblast feeder layer viability. Therefore, the thorough understanding of the impact of different issues such as culture media composition, irradiation dose and pre-plating storage conditions of irradiated fibroblast to be used as feeder layer in these co-culture systems is important. In this work, changes as far as viability and proliferative rates of irradiated fibroblasts in culture were evaluated in relation to the type of culture medium used, dose of gamma radiation exposure, storage and timing of cell plating post irradiation. Results indicate that the type of culture medium used and time-lag between irradiation, refrigeration and plating of irradiated cells do not have significant impact in culture outcomes. However, the dose of gamma radiation administered to the cells may influence the final quality of these cells if to be used as a feeder layer. (author)

  4. Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ.

    Science.gov (United States)

    Kreutzer, U; Mekhamer, Y; Chung, Y; Jue, T

    2001-05-01

    The 1H-NMR signal of the proximal histidyl-N(delta)H of deoxymyoglobin is detectable in the in situ rat myocardium and can reflect the intracellular PO2. Under basal normoxic conditions, the cellular PO2 is sufficient to saturate myoglobin (Mb). No proximal histidyl signal of Mb is detectable. On ligation of the left anterior descending coronary artery, the Mb signal at 78 parts/million (ppm) appears, along with a peak shoulder assigned to the corresponding signal of Hb. During dopamine infusion up to 80 microg. kg(-1) x min(-1), both the heart rate-pressure product (RPP) and myocardial oxygen consumption (MVO2) increase by about a factor of 2. Coronary flow increases by 84%, and O2 extraction (arteriovenous O2 difference) rises by 31%. Despite the increased respiration and work, no deoxymyoglobin signal is detected, implying that the intracellular O2 level still saturates MbO2, well above the PO2 at 50% saturation of Mb. The phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and the ratio of the change in P(i) over PCr (DeltaP(i)/PCr) increases by 0.19. Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a pyruvate dehydrogenase activator, abolishes the change in DeltaP(i)/PCr. Intracellular O2 supply does not limit MVO2, and the role of ADP in regulating respiration in rat myocardium in vivo remains an open question.

  5. The influence of psycho-emotional stress in children of primary school age on the incidence of recurrent upper respiratory tract infections and the functional state of the myocardium

    Directory of Open Access Journals (Sweden)

    L.S. Ovcharenko

    2017-10-01

    Full Text Available Background. Scientific and technical progress, intensification of educational process and information overload have a negative effect on unformed central nervous system of primary schoolchildren, causing stress, which affects the increase in the incidence of recurrent upper respiratory tract infections (URTI and the functional state of the myocardium. In view of this, we analyzed a functional state of myocardium in children with recurrent URTI. The critical duration of the work of primary school child with electronic means of communication, which affects the quality of nighttime sleep and the nature of awakening in the morning, was established. We have studied the relationship of the above mentioned with the incidence of URTI, the level of school anxiety and functional reserve of the myocardium. The purpose of the study was to evaluate the functional reserve of the myocardium in children of primary school age, depending on the incidence of URTI and the level of psycho-emotional activity. Materials and me­thods. 239 children aged 6 to 9 years were examined. The analysis of the functional reserve of the myocardium was carried out in pupils with different incidence of the URTI, depending on the age. The influence of electronic communications on the quality of nighttime sleep and morning awakening was stu­died, and the level of school anxiety was evaluated. During the study, children were divided into two groups. Group 1 — children with recurrent acute respiratory diseases (n = 143. Group 2 — children who occasionally have URTI (n = 96. Results. Out of 239 children with recurrent acute respiratory infections, we have identified 173 children with reduced functional reserve of the myocardium (72.4 %. Among children with recurrent URTI, the incidence of reduced functional reserve of the myocardium was 76.2 %, and in occasionally ill children — 66.7 %. Children with recurrent URTI use electronic means of communication more often than

  6. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  7. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  8. The contribution of nuclear medicine in the six months following a myocardium infarction

    International Nuclear Information System (INIS)

    Franken, Ph.R.

    2002-01-01

    The techniques of nuclear medicine allow to estimate the myocardial infarction size, to measure the ejection fraction and the ventricles volumes and to identify the presence of high-risk and viable myocardium. This information is essential to evaluate the important complications risks after an acute myocardial infarction, that is to say the infarction recurrence and the cardiac death coming from rhythm troubles or a left ventricle failure. (N.C.)

  9. Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab

    International Nuclear Information System (INIS)

    Johnson, L.L.; Lerrick, K.S.; Coromilas, J.

    1987-01-01

    Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent

  10. Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

    Science.gov (United States)

    Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

    2013-11-01

    High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, pursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

  11. Metabolic borderzone in acutely ischemic canine myocardium demonstrated by positron-CT (PCT)

    International Nuclear Information System (INIS)

    Schwaiger, M.; Hansen, H.; Selin, C.; Wittmer, S.; Barrio, J.; Schelbert, H.R.

    1984-01-01

    Acute coronary ligation in dogs results in an area of myocardial dysfunction that exceeds the area of subsequent necrosis suggesting the existence of an ischemic ''borderzone'' of reversibly injured myocardium. The authors tested this hypothesis in 9 closed chest dogs with C-11 plamitate (CPA) and serial PCT imaging after an LAD occlusion. Using a blood flow (MBF) image obtained with iv N-13 ammonia prior to CPA, regions of interest were assigned on the serial CPA cross-sectional images to the center (IC) and border (IB) of the ischemic segment and to control myocardium (CO). CPA uptake was closely related to MBF (r=0.88) implicating flow as a major determinant of CPA uptake. Clearance helftimes (T 1/2) and relative sizes (RS) of the early rapid phase on the C-11 tissue time activity curves were determined for IC, IB and CO. In IC, MBF, RS and T 1/2 were markedly depressed indicating impaired CPA utilization and oxidation. In IB, MBF was less than in CO though only insignificantly, while RS and T 1/2 were highly abnormal. The authors conclude that FFA metabolism in areas adjacent to ischemic segments but without significant MBF decreases in abnormal, presenting evidence for a metabolic borderzone which now can be identified noninvasively with positron emission tomography

  12. No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

    Directory of Open Access Journals (Sweden)

    Nilgün Gedik

    Full Text Available Remote ischemic preconditioning (RIPC by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG. Activation of signal transducer and activator of transcription 5 (STAT5 in left ventricular (LV myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation or placebo (cuff deflated before skin incision (n = 10/10. Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline and at early (5-10 min reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002. Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12 complex, light chain 3 (LC3, parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02. STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05.Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

  13. Sensitization of the Guinea Pig Myocardium through the Mucous Membrane of the Digestive Tract,

    Science.gov (United States)

    Under certain conditions, sessile antibodies can be bound by the guinea - pig myocardium that had been sensitized by direct introduction of the allergen into the stomach. This is confirmed by the positive anaphylactic reaction in the isolated heart of animals treated in this manner, which reaction manifests itself in a modified heart rate when the isolated heart is challenged by the sensitizing allergen.

  14. 99Tcm-MIBI imaging with liposomal prostaglandin E1 infusion to detect viable myocardium in post-myocardial infarction patients

    International Nuclear Information System (INIS)

    Zheng Yong; Cai Hongbin; Miao Weibing; Lin Jun; Pan Runyang; Lin Haoxue

    2007-01-01

    Objective: The pharmacological efficiencies of liposomal prostaglandin E 1 (Lipo-PGE 1 ) infusion and nitrate infusion on 99 Tc m -methoxyisobutylisonitrile (MIBI) imaging detection of viable myocardium in post-myocardial infarction (MI) patients were compared in the current study. Methods: Thirty-two patients with MI underwent 99 Tc m -MIBI imaging at rest, nitrate infusion and Lipo-PGE 1 infusion respectively. The semi-quantitative analysis of 99 Tc m -MIBI imaging was carried out in 16 segments over each left ventricle. Results: Abnormal 99 Tc m -MIBI distribution in 216 segments (42.2%) at rest, 178 segments (34.8%) at nitrate infusion, and 184 segments (35.9%) at Lipo-PGE 1 infusion were identified. Among the 216 abnormal segments at rest, 89 (41.2%) and 81 (37.5%) were found improved after nitrate infusion and Lipo-PGE 1 infusion respectively. Detecting viable myocardium with Lipo-PGE 1 infusion imaging was accordant with that of nitrate infusion imaging in 89.8% of the cases. The mean uptake scores of abnormal segments at rest, nitrate infusion, and Lipo-PGE 1 infusion were 15.3 ± 3.3, 10.5 ± 1.4 (P 1 infusion imaging can be used for detection of viable myocardium in patients with MI. (authors)

  15. Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma Irradiation.

    Science.gov (United States)

    Sugaya, Kimihiko; Hirobe, Tomohisa; Ishihara, Yoshie; Inoue, Sonoe

    2016-10-01

    To determine whether the effects of low-dose-rate gamma (γ) irradiation are identifiable in the regeneration of murine hair follicles, we irradiated whole bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with 137 Cs γ-rays. The mice were examined for effects on hair follicles, including number, morphology, and pigmentation in the second anagen phase. Effects of γ-radiation on melanocyte stem cells were also investigated by the indirect immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a decrease in hair follicle density and the induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs. There was a small, but not significant, change in the number of TRP2-positive melanocyte stem cells in the hair bulge region of the irradiated skin. These results suggest that low-dose rate γ-irradiation does not deplete melanocyte stem cells, but can damage stem cells and progenitors for both keratinocytes and melanocytes, thereby affecting the structure and pigmentation of regenerated hair follicles in the 2 nd anagen phase.

  16. Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Falk, Bo Torkel; Jönsson, Lennart; Olsen, Lisbeth Høier

    2006-01-01

    Background: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. Methods: Twenty-one dogs with naturally occurring congestive heart failure and 21 age......-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta...... and pulmonary artery. Results: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (Pdogs. However...

  17. Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

    Science.gov (United States)

    Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

    2017-01-01

    Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

  18. Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin.

    Science.gov (United States)

    Bennett, Jared R; Lateef, Zabeen; Fleming, Stephen B; Mercer, Andrew A; Wise, Lyn M

    2016-02-02

    Orf virus (ORFV) is a zoonotic parapoxvirus that causes pustular dermatitis of sheep, and occasionally humans. Despite causing sustained infections, ORFV induces only a transient increase in pro-inflammatory signalling and the trafficking of innate immune cells within the skin seems to be impaired. An explanation for this tempered response to ORFV infection may lie in its expression of a homolog of the anti-inflammatory cytokine, interleukin (IL)-10. Using a murine model in which inflammation was induced by bacterial lipopolysaccharide, we examined the effects of the ORFV-IL-10 protein on immune cell trafficking to and from the skin. ORFV-IL-10 limited the recruitment of blood-derived Gr-1(int)/CD11b(int) monocytes, CD11c(+ve)/MHC-II(+ve) dendritic cells and c-kit(+ve)/FcεR1(+ve) mature mast cells into inflamed skin. ORFV-IL-10 also suppressed the activation of CD11c(+ve)/MHC-II(+ve) dendritic cells within the skin, reducing their trafficking to the draining lymph node. These findings suggest that expression of IL-10 by ORFV may contribute to the impaired trafficking of innate immune cells within infected skin. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Synchronous In Situ ATPase Activity, Mechanics, and Ca2+ Sensitivity of Human and Porcine Myocardium

    Czech Academy of Sciences Publication Activity Database

    Griffiths, P. J.; Isackson, H.; Pelc, Radek; Redwood, C.S.; Funari, S.S.; Watkins, H.; Ashley, C. C.

    2009-01-01

    Roč. 97, č. 9 (2009), s. 2503-2512 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LC06063 Grant - others:EC(XE) RII3-CT-2004-506008 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardium * actomyosin- ATPase * synchrotron-radiation Subject RIV: ED - Physiology Impact factor: 4.390, year: 2009

  20. Experimental basis of metabolic imaging of the myocardium with radioiodinated aromatic free fatty acids

    International Nuclear Information System (INIS)

    Reske, S.N.; Knapp, F.F. Jr.; Winkler, C.

    1986-01-01

    For the investigation of myocardial perfusion and left ventricular pump function, advanced radioisotopic techniques have been established. New developments in radiopharmacology and single-photon emission computed tomography have recently enabled the investigation of parameters of regional energy metabolism in well defined areas of the heart muscle. For this purpose, various iodine ( 123 I)-labeled free fatty acids (FFA) have been synthesized. The diagnostic application of labeled FFA in heart disease may be important, since FFA are the preferred substrates for cardiac energy production at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation which is extremely sensitive to oxygen deprivation. This article outlines the basic physiologic pathways of FFA in normal and ischemic myocardium and reviews the results of animal experiments validating the application of these principles for metabolic imaging of the heart by means of the aromatic radioiodinated FFA, 15-(p-iodophenyl)pentadecanoic acid. In addition, the development, physiologic properties, and potential applications of a new generation of 3-methyl-substituted radioiodinated fatty acids that show high myocardial uptake but prolonged retention are discussed. 64 references

  1. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  2. Effect of synthetic vernix biofilms on barrier recovery of damaged mouse skin.

    Science.gov (United States)

    Oudshoorn, Marion H M; Rissmann, Robert; van der Coelen, Dennis; Hennink, Wim E; Ponec, Maria; Bouwstra, Joke A

    2009-08-01

    The aim of this work was to investigate whether topical application of synthetic biofilms supports and accelerates the recovery of the murine skin barrier, disrupted by sequential tape stripping. Therefore, various biofilms were applied topically on disrupted mouse skin to determine which formulation could improve barrier function, as was observed previously for the natural biofilm vernix caseosa (VC). The biofilms [i.e. particles (synthetic corneocytes) embedded in a synthetic lipid matrix] mimic closely the physicochemical properties and structure of VC. Various formulations were prepared using different particle:lipid ratios, particles with different initial water content and uncoated or lipid-coated particles. It was observed that application of all tested formulations improved the skin barrier recovery rate and reduced crust formation and epidermal hyperproliferation. However, only one of the biofilms [i.e. B1; composed of uncoated particles with 50% (w/w) initial water content and particle:lipid ratio of 2:1] mimicked the effects of native VC most closely. This indicates the importance of the presence of individual components, i.e. barrier lipids and water, as well as the ratio of these components. Consequently, these observations suggest the potential use of this biofilm treatment clinically.

  3. Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Tomoya Watanabe

    Full Text Available The murine bleomycin (BLM-induced fibrosis model is the most widely used in systemic sclerosis (SSc studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

  4. Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial.

    Science.gov (United States)

    Deja, Marek A; Wiaderkiewicz, Ryszard; Czekaj, Piotr; Czech, Ewa; Malinowski, Marcin; Machej, Leszek; Węglarzy, Andrzej; Kowalówka, Adam; Piekarska, Magda; Szurlej, Bartosz; Latusek, Tomasz

    2018-01-01

    Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical

  5. Effect of vanadate and of removal of extracellular Ca2+ and Na+ on tension development and 45Ca efflux in rat and frog myocardium

    DEFF Research Database (Denmark)

    Gesser, H; Bonefeld-Jørgensen, Eva Cecilie

    1983-01-01

    Vanadate in the range 0-5 mM has positive inotropic effects on myocardial strips of frog and to a lesser extent on those of rat. Inhibiting the sarcolemmal Na+, Ca2+ exchange by a solution free of Ca2+ and Na+ caused a drop in 45Ca efflux and a transient increase in resting tension. These effects...... were more expressed for the frog than for the rat myocardium, which suggests that the Na+ for Ca2+ exchange across the cell membrane is more important in the frog than in the rat myocardium. A subsequent addition of vanadate at 2 or 5 mM had no effect on 45Ca efflux, while it increased the resting...... tension. This increase was higher for the frog than for the rat myocardium. These results suggest that the inotropic effects of vanadate may be due to an effect on membrane-bound Ca2+-ATPase....

  6. Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

    Science.gov (United States)

    Mori, Ryoichi; Tanaka, Katsuya; de Kerckhove, Maiko; Okamoto, Momoko; Kashiyama, Kazuya; Tanaka, Katsumi; Kim, Sangeun; Kawata, Takuya; Komatsu, Toshimitsu; Park, Seongjoon; Ikematsu, Kazuya; Hirano, Akiyoshi; Martin, Paul; Shimokawa, Isao

    2014-09-01

    The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging

    International Nuclear Information System (INIS)

    Dilsizian, V.; Rocco, T.P.; Freedman, N.M.; Leon, M.B.; Bonow, R.O.

    1990-01-01

    The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not fill in on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium. We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed. Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty

  8. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.

    Directory of Open Access Journals (Sweden)

    Natalia Smorodinova

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients.The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR.We examined 46 subjects (19 with AF, and 27 in SR undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry.The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample.An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

  9. Resveratrol Derivative-Rich Melinjo Seed Extract Attenuates Skin Atrophy in Sod1-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2015-01-01

    Full Text Available The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1 resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemon Linn seed extract (MSE contains trans-resveratrol (RSV and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in the Sod1−/− mice. Furthermore, MSE and RSV normalized gene expression of Col1a1 and p53 and upregulated gene expression of Sirt1 in skin tissues. In vitro experiments revealed that RSV significantly promoted the viability of Sod1−/− fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivo and in vitro leading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.

  10. Effects of a new bifunctional psoralen, 4,4',5'-trimethylazapsoralen and ultraviolet-A radiation on murine dendritic epidermal cells.

    Science.gov (United States)

    Aubin, F; Alcalay, J; Dall'Acqua, F; Kripke, M L

    1990-06-01

    Although some psoralens are therapeutically active in the treatment of cutaneous hyperproliferative diseases when combined with UVA (320-400 nm) radiation, the toxic effects of these compounds have led physicians to seek new photochemotherapeutic agents. One such agent is 4,4',5'-trimethylazapsoralen (TMAP), a new bifunctional psoralen compound. We investigated the effects of repetitive treatments with TMAP plus UVA radiation on the number of dendritic immune cells in murine epidermis and on the induction of phototoxicity. Mice treated 3 times per week for 4 weeks with 129 microgram TMAP plus 10 kJ/m2 UVA radiation exhibited no gross or microscopic evidence of phototoxicity. During this treatment, the numbers of ATPase+, Ia+, and Thy-l+ dendritic epidermal cells were greatly reduced, and by the end of the treatment period, few dendritic immune cells could be detected. We conclude that morphological alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that TMAP plus low-dose UVA radiation decreases the numbers of detectable Langerhans cells and Thy-1+ cells in murine skin.

  11. Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

    Directory of Open Access Journals (Sweden)

    Rui Hua

    Full Text Available Phosphodiesterases (PDEs are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+ current (I(Ca,L is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP properties and I(Ca,L in the sinoatrial node (SAN and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA, the PDE3 inhibitor milrinone (Mil and the PDE4 inhibitor rolipram (Rol. In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L. In complete contrast, no selective PDE inhibitors increased I(Ca,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium.

  12. The effect of mixed fractionation with X rays and neutrons on tumour growth delay and skin reactions in mice

    International Nuclear Information System (INIS)

    Carl, U.M.

    1987-01-01

    The authors have compared the effects of mixed fractionation schedules with X rays and neutrons on growth delay of a murine tumour and skin reactions in mice. The schedules were five daily fractions of X rays, neutrons or mixtures (NNXXX, XXXNN or NXXXN). For clamped tumours or skin all three mixed schedules had the same effect. In contrast, for unclamped tumours giving the neutrons first (NNXXX) was more effective than the other two mixed schedules. This represented a true therapeutic gain and implies that if neutrons are used clinically as only part of a course of fractionated radiotherapy, they should be given at the beginning rather than at the end of treatment. (author)

  13. Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

    Science.gov (United States)

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

    2016-01-01

    Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

  14. Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

    DEFF Research Database (Denmark)

    Fritz-Hansen, T; Rostrup, Egill; Søndergaard, Lise

    1998-01-01

    The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole...

  15. Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.

    Science.gov (United States)

    Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean-Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C; Bhakoo, Kishore K

    2015-06-01

    The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Delayed contrast enhancement imaging of a murine model for ischemia reperfusion with carbon nanotube micro-CT.

    Directory of Open Access Journals (Sweden)

    Laurel M Burk

    Full Text Available We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating. Using free-breathing, cardiac-gated CNT micro-CT, a myocardial infarction model can be studied non-invasively and with high resolution. Myocardial infarction was induced in eight male C57BL/6 mice aged 8-12 weeks. The ischemia reperfusion model was achieved by surgically occluding the LAD artery for 30 minutes followed by 24 hours of reperfusion. Tail vein catheters were placed for contrast administration. Iohexol 300 mgI/mL was administered followed by images obtained in diastole. Iodinated lipid blood pool contrast agent was then administered, followed with images at systole and diastole. Respiratory and cardiac signals were monitored externally and used to gate the scans of free-breathing subjects. Seven control animals were scanned using the same imaging protocol. After imaging, the heart was harvested, cut into 1mm slices and stained with TTC. Post-processing analysis was performed using ITK-Snap and MATLAB. All animals demonstrated obvious delayed contrast enhancement in the left ventricular wall following the Iohexol injection. The blood pool contrast agent revealed significant changes in cardiac function quantified by 3-D volume ejection fractions. All subjects demonstrated areas of myocardial infarct in the LAD distribution on both TTC staining and micro-CT imaging. The CNT micro-CT system aids straightforward, free-breathing, prospectively-gated 3-D murine cardiac imaging. Delayed contrast enhancement allows identification of infarcted myocardium after a myocardial ischemic

  17. Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.

    Science.gov (United States)

    Wang, Qin; Yang, Shengwei; Jiang, Cuihua; Li, Jindian; Wang, Cong; Chen, Linwei; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-02-16

    Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.

  18. Pathomorphological Changes of the Myocardium in Canine Dilated Cardiomyopathy (DCM

    Directory of Open Access Journals (Sweden)

    Janus Izabela

    2015-04-01

    Full Text Available The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration, vascular changes (congestion and coronary vessel wall hypertrophy, degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure, and presence of inflammatory infiltrates (mononuclear and polynuclear were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.

  19. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

    Directory of Open Access Journals (Sweden)

    Kei Takahashi

    Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  20. QSAR Study of Skin Sensitization Using Local Lymph Node Assay Data

    Directory of Open Access Journals (Sweden)

    Eugene Demchuk

    2004-01-01

    Full Text Available Abstract: Allergic Contact Dermatitis (ACD is a common work-related skin disease that often develops as a result of repetitive skin exposures to a sensitizing chemical agent. A variety of experimental tests have been suggested to assess the skin sensitization potential. We applied a method of Quantitative Structure-Activity Relationship (QSAR to relate measured and calculated physical-chemical properties of chemical compounds to their sensitization potential. Using statistical methods, each of these properties, called molecular descriptors, was tested for its propensity to predict the sensitization potential. A few of the most informative descriptors were subsequently selected to build a model of skin sensitization. In this work sensitization data for the murine Local Lymph Node Assay (LLNA were used. In principle, LLNA provides a standardized continuous scale suitable for quantitative assessment of skin sensitization. However, at present many LLNA results are still reported on a dichotomous scale, which is consistent with the scale of guinea pig tests, which were widely used in past years. Therefore, in this study only a dichotomous version of the LLNA data was used. To the statistical end, we relied on the logistic regression approach. This approach provides a statistical tool for investigating and predicting skin sensitization that is expressed only in categorical terms of activity and nonactivity. Based on the data of compounds used in this study, our results suggest a QSAR model of ACD that is based on the following descriptors: nDB (number of double bonds, C-003 (number of CHR3 molecular subfragments, GATS6M (autocorrelation coefficient and HATS6m (GETAWAY descriptor, although the relevance of the identified descriptors to the continuous ACD QSAR has yet to be shown. The proposed QSAR model gives a percentage of positively predicted responses of 83% on the training set of compounds, and in cross validation it correctly identifies 79% of

  1. Photoprotection of Buddleja cordata extract against UVB-induced skin damage in SKH-1 hairless mice.

    Science.gov (United States)

    Avila Acevedo, José Guillermo; Espinosa González, Adriana Montserrat; De Maria y Campos, Diana Matamoros; Benitez Flores, José del Carmen; Hernández Delgado, Tzasna; Flores Maya, Saul; Campos Contreras, Jorge; Muñoz López, José Luis; García Bores, Ana María

    2014-08-03

    In recent years, there has been considerable interest in using botanical agents to prevent skin damage resulting from solar UV-irradiation. Buddleja cordata is a plant that is known as "tepozan". Some people in Mexico use the leaves of this plant to treat tumours, abscesses, sores and burns. The purpose of this study is to investigate the photoprotective properties of Buddleja cordata methanolic extract (BCME) against UVB-induced skin damage in SKH-1 hairless mice at the macroscopic and histological levels. BCME was characterised to determine its spectroscopic, chromatographic and antioxidant (DPPH, superoxide and hydroxyl radicals) properties. To conduct the photoprotection studies, BCME was applied topically to the skin of SKH-1 mice before acute exposure to UVB for 10 minutes. The murine skin samples were used for macroscopic and histological studies to assess tissue damage. Penetration of active components of BCME into stratum corneum on the dorsal area of mice was investigated in vivo by the tape stripping method. Moreover, genotoxicity of BCME was evaluated in a Vicia faba cell root micronucleus model. BCME displayed absorbance over the entire UVB spectrum, and its principal components included verbascoside and linarin. BCME exhibited antioxidant activity and significantly scavenged hydroxyl radicals. BCME reduced erythema, sunburn cell production, vessel congestion and epidermal thickening of UVB irradiated mouse skin. BCME penetrate the skin of mice. BCME did not exhibit genotoxic activity in the micronucleus test. The topical administration of BCME protected against acute UVB-induced damage in mouse SKH-1 skin, and our results suggest that BCME may potentially prevent photodamage.

  2. Stereoselective handling of perhexiline: implications regarding accumulation within the human myocardium.

    Science.gov (United States)

    Chong, Cher-Rin; Drury, Nigel E; Licari, Giovanni; Frenneaux, Michael P; Horowitz, John D; Pagano, Domenico; Sallustio, Benedetta C

    2015-12-01

    Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: β = -0.256, p = 0.015; (-) perhexiline: β = -0.347, p = 0.001] and patients' age [(+) perhexiline: β = 0.300, p = 0.004; (-) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (β = -0.240, p = 0.015). (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.

  3. Gene Silencing in Skin After Deposition of Self-Delivery siRNA With a Motorized Microneedle Array Device

    Directory of Open Access Journals (Sweden)

    Robyn P Hickerson

    2013-01-01

    Full Text Available Despite the development of potent siRNAs that effectively target genes responsible for skin disorders, translation to the clinic has been hampered by inefficient delivery through the stratum corneum barrier and into the live cells of the epidermis. Although hypodermic needles can be used to transport siRNA through the stratum corneum, this approach is limited by pain caused by the injection and the small volume of tissue that can be accessed by each injection. The use of microneedle arrays is a less painful method for siRNA delivery, but restricted payload capacity limits this approach to highly potent molecules. To address these challenges, a commercially available motorized microneedle array skin delivery device was evaluated. This device combines the positive elements of both hypodermic needles and microneedle array technologies with little or no pain to the patient. Application of fluorescently tagged self-delivery (sd-siRNA to both human and murine skin resulted in distribution throughout the treated skin. In addition, efficient silencing (78% average reduction of reporter gene expression was achieved in a transgenic fluorescent reporter mouse skin model. These results indicate that this device effectively delivers functional sd-siRNA with an efficiency that predicts successful clinical translation.

  4. Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

    Science.gov (United States)

    Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

    2012-12-01

    The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, Prespiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, Pacidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

  5. Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy

    Science.gov (United States)

    Bancelin, Stéphane; Lynch, Barbara; Bonod-Bidaud, Christelle; Ducourthial, Guillaume; Psilodimitrakopoulos, Sotiris; Dokládal, Petr; Allain, Jean-Marc; Schanne-Klein, Marie-Claire; Ruggiero, Florence

    2015-12-01

    Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.

  6. Early assessment of tissue viability with radioiodinated heptadecanoic acid in reperfused canine myocardium: Comparison with thallium-201

    International Nuclear Information System (INIS)

    Chappuis, F.; Meier, B.; Belenger, J.; Blaeuenstein, P.L.; Lerch, R.

    1990-01-01

    Myocardial scintigraphy with heptadecanoic acid labeled with iodine-123 (123I-HDA) may allow early noninvasive delineation of viable myocardium after reperfusion. In this study myocardial uptake of 123I-HDA was compared with that of thallium-201 in six closed-chest dogs after 5 hours of occlusion followed by 1 hour of reperfusion of the left anterior descending coronary artery. Myocardial blood flow was measured with microspheres, and myocardial viability was assessed by means of triphenyltetrazolium chloride staining. In viable areas of the reperfused region, 123I-HDA uptake, thallium-201 uptake, and myocardial blood flow were similar to those measured in the control circumflex region. However, in infarcted areas they were reduced to 48 +/- 2% (mean +/- SEM; p less than 0.001), 59 +/- 3% (p less than 0.001), and 74 +/- 5% (p less than 0.001) of control values, respectively. Results of multiple regression analysis showed that thallium-201 uptake primarily reflected the level of flow during reperfusion, whereas 123I-HDA uptake was dependent on both myocardial blood flow and viability. At each level of flow, 123I-HDA uptake was significantly lower in infarcted than in viable myocardium. By means of discriminant analysis, 123I-HDA uptake was found to be the single most important predictor of viability, whereas thallium-201 was only of limited importance. Myocardial 123I-HDA uptake greater than or equal to 71% or myocardial thallium-201 uptake greater than or equal to 73% best differentiated viable from infarcted myocardium. According to these criteria, 123I-HDA predicted myocardial viability with a sensitivity of 77%, a specificity of 84% and a predictive accuracy of 81%

  7. Temperature dependence of the kinetics of isometric myocardium relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Izakov, V.Ya.; Bykov, B.L.; Kimmelman, I.Ya.

    1981-11-01

    The dependence of the exponential decay constant expressing the isometric relaxation of the myocardium on temperature is investigated in animals with various specific contents of myocardial sarcoplasmic reticulum. Experiments were performed on cardiac ventricles and atria isolated from rabbits, frogs and turtles and electrically stimulated to produce maximal contraction at temperatures from 10 to 35 C. Arrhenius plots derived from the data are found to be linear in the myocardia of the rabbit and frog, with a greater activation energy for the relaxation found in the rabbit. The Arrhenius plot for the turtle, which has a sarcoplasmic reticulum content intermediate between those of the frog and rabbit, corresponds to two straight lines with different activation energies. Results thus support the hypothesis of two separate mechanisms of calcium removal, involving the sarcoplasmic reticulum and cellular membrane, in muscle relaxation.

  8. 99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

    International Nuclear Information System (INIS)

    Okada, David R.; Liu, Zhonglin; Johnson, Gerald; Okada, Robert D.; Beju, Delia; Khaw, Ban An

    2010-01-01

    99m Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine 99m Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). 99m Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. 99m Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 ± 0.09) (cpm, SEM) than in control (1.74 ± 0.07), stunned (1.68 ± 0.11), and hibernating (1.59 ± 0.11) (p 99m Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 ± 0.63) than in control (1.98 ± 0.15), stunned (1.79 ± 0.08), and hibernating (2.33 ± 0.15) (p 99m Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. 99m Tc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar 99m Tc-glucarate uptakes in control, stunned, and hibernating myocardium. (orig.)

  9. 99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

    International Nuclear Information System (INIS)

    Hoffend, J.; Linke, G.; Mohammed, A.; Haberkorn, U.; Tiefenbacher, C.P.; Eisenhut, M.

    2003-01-01

    Myocardial perfusion single-photon emission tomography (SPET) performed with cationic technetium-99m complexes indicates ischaemic areas as cold lesions. By contrast, nitroimidazole derivatives labelled with fluorine-18 or 99m Tc have recently shown promising results for hot spot imaging of ischaemic myocardium. This study evaluates 99m TcO(BAT-NI), a new 99m Tc complex comprising the nitroimidazole ligand, 2,10-dimercapto-2, 10-dimethyl-4, 8-diaza-6-[4-(2-nitroimidazolyl)butyl]undecane, in a low-flow in vivo model of myocardial ischaemia in thoracotomised rats. To elucidate the influence of the 2-nitroimidazole group on ischaemia-induced uptake, comparisons with ligand derivatives were performed where (a) the 2-nitro group was deleted [ 99m TcO(BAT-I)], (b) the 2-nitroimidazole functionality was replaced by a Br atom [ 99m TcO(BAT-Br)] and (c) the 99m TcO(BAT) moiety was replaced by an iodine-125 iodophenoxybutyl ligand ( 125 IP-NI). The radiolabelled compounds were i.v. injected 15 min after reducing resting myocardial blood flow by 50-60% and the uptake of radioactivity was assessed 90 min post injection. Autoradiography of left ventricular short-axis slices showed median uptake ratios of ischaemic/non-ischaemic myocardium (I/N) of 3.4, 4.5 and 3.4 for 99m TcO(BAT-NI), 99m TcO(BAT-I) and 99m TcO(BAT-Br), respectively. In contrast, 125 IP-NI was not preferentially taken up by ischaemic myocardium. Accumulation of 99m TcO(BAT-NI) in ischaemic heart regions was comparable to that in the liver. Biodistribution studies showed a median uptake of 0.65% ID/g of 99m TcO(BAT-NI) in ischaemic tissue and an I/N of 3.3. On planar images of the thorax and upper abdomen the ischaemic hearts were visualised faintly; the median heart to lung count ratio for 99m TcO(BAT-NI) was 1.7, and the median heart to liver count ratio was 1.0. We conclude that uptake of 99m TcO(BAT-NI) in ischaemic myocardium does not depend on the nitroimidazole moiety but is intrinsic to the BAT complex

  10. Dynamic Wnt5a expression in murine hair follicle cycle and its inhibitory effects on follicular.

    Science.gov (United States)

    Fang, De-Ren; Lv, Zhong-Fa; Qiao, Gang

    2014-04-01

    To analyze the dynamic expression of Wnt family member 5A (Wingless-type MMTV integration Wnt site family, member 5a) in murine hair cycle and its inhibitory effects on follicle in vivo. Situ hybridization in full-thickness skin was used to observe the change of mouse protein expression in different growth stages, and Ad-Wnt5a was injected after defeathering to observe the hair follicle growth in vivo. The Wnt5a mRNA was expressed at birth, and was firstly increased then decreased along with the progress of the hair cycle. It reached the peak in advanced stage of growth cycle (P<0.05). Rhoa and β-catenin expression levels were significantly decreased in three groups. Rac2 expression was significantly up-regulated, and the expression level of Wnt5a, Shh and Frizzled2 was increased, but less significantly than group 2. The expression of Wnt5a mRNA is consistent with change of murine follicle cycle, and has obvious inhibitory effects on the growth of hair follicle in vivo, indicating that it is antagonistic to Wnts pathway and interferes the growth of follicle together. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  11. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  12. Anatomy and Histology of the Human and Murine Prostate.

    Science.gov (United States)

    Ittmann, Michael

    2018-05-01

    The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  13. Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes

    DEFF Research Database (Denmark)

    Larsen, Julie; Bushnell, Peter; Steffensen, John

    2017-01-01

    We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca2+ release from the sarcoplasmic reticulum (SR) with ryanodine...... positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark...... at 30 °C; indicating that SR involvement in excitation–contraction (EC) coupling is species- and temperature-specific in elasmobranch fishes, as it is in teleost fishes. Atrial and ventricular myocardium from all three species displayed a negative force–frequency relationship, but there was no evidence...

  14. Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise

    Directory of Open Access Journals (Sweden)

    Rostika Flora

    2012-08-01

    Full Text Available Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α. The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05 in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66. Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35, while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73. The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59 in the aerobic group and strong in the anaerobic group (r = 0.69.Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40Keywords: Exercise, HIF-1α, myocardium, VEGF

  15. Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Sjögren Jane

    2012-01-01

    Full Text Available Abstract Background T2-weighted cardiovascular magnetic resonance (CMR has been shown to be a promising technique for determination of ischemic myocardium, referred to as myocardium at risk (MaR, after an acute coronary event. Quantification of MaR in T2-weighted CMR has been proposed to be performed by manual delineation or the threshold methods of two standard deviations from remote (2SD, full width half maximum intensity (FWHM or Otsu. However, manual delineation is subjective and threshold methods have inherent limitations related to threshold definition and lack of a priori information about cardiac anatomy and physiology. Therefore, the aim of this study was to develop an automatic segmentation algorithm for quantification of MaR using anatomical a priori information. Methods Forty-seven patients with first-time acute ST-elevation myocardial infarction underwent T2-weighted CMR within 1 week after admission. Endocardial and epicardial borders of the left ventricle, as well as the hyper enhanced MaR regions were manually delineated by experienced observers and used as reference method. A new automatic segmentation algorithm, called Segment MaR, defines the MaR region as the continuous region most probable of being MaR, by estimating the intensities of normal myocardium and MaR with an expectation maximization algorithm and restricting the MaR region by an a priori model of the maximal extent for the user defined culprit artery. The segmentation by Segment MaR was compared against inter observer variability of manual delineation and the threshold methods of 2SD, FWHM and Otsu. Results MaR was 32.9 ± 10.9% of left ventricular mass (LVM when assessed by the reference observer and 31.0 ± 8.8% of LVM assessed by Segment MaR. The bias and correlation was, -1.9 ± 6.4% of LVM, R = 0.81 (p Conclusions There is a good agreement between automatic Segment MaR and manually assessed MaR in T2-weighted CMR. Thus, the proposed algorithm seems to be a

  16. Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance.

    Science.gov (United States)

    Sjögren, Jane; Ubachs, Joey F A; Engblom, Henrik; Carlsson, Marcus; Arheden, Håkan; Heiberg, Einar

    2012-01-31

    T2-weighted cardiovascular magnetic resonance (CMR) has been shown to be a promising technique for determination of ischemic myocardium, referred to as myocardium at risk (MaR), after an acute coronary event. Quantification of MaR in T2-weighted CMR has been proposed to be performed by manual delineation or the threshold methods of two standard deviations from remote (2SD), full width half maximum intensity (FWHM) or Otsu. However, manual delineation is subjective and threshold methods have inherent limitations related to threshold definition and lack of a priori information about cardiac anatomy and physiology. Therefore, the aim of this study was to develop an automatic segmentation algorithm for quantification of MaR using anatomical a priori information. Forty-seven patients with first-time acute ST-elevation myocardial infarction underwent T2-weighted CMR within 1 week after admission. Endocardial and epicardial borders of the left ventricle, as well as the hyper enhanced MaR regions were manually delineated by experienced observers and used as reference method. A new automatic segmentation algorithm, called Segment MaR, defines the MaR region as the continuous region most probable of being MaR, by estimating the intensities of normal myocardium and MaR with an expectation maximization algorithm and restricting the MaR region by an a priori model of the maximal extent for the user defined culprit artery. The segmentation by Segment MaR was compared against inter observer variability of manual delineation and the threshold methods of 2SD, FWHM and Otsu. MaR was 32.9 ± 10.9% of left ventricular mass (LVM) when assessed by the reference observer and 31.0 ± 8.8% of LVM assessed by Segment MaR. The bias and correlation was, -1.9 ± 6.4% of LVM, R = 0.81 (p Segment MaR, -2.3 ± 4.9%, R = 0.91 (p Segment MaR and manually assessed MaR in T2-weighted CMR. Thus, the proposed algorithm seems to be a promising, objective method for standardized MaR quantification in T2

  17. Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

    Science.gov (United States)

    Makarov, G. A.

    1980-01-01

    Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia.

  18. Ambient humidity and the skin: the impact of air humidity in healthy and diseased states.

    Science.gov (United States)

    Goad, N; Gawkrodger, D J

    2016-08-01

    Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further

  19. Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Vilcek, S; Machan, V; Kalincak, M [Ustav Radioekologie a Vyuzitia Jadrovej Techniky, Kosice (Czechoslovakia); Nicak, A [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Lekarska Fakulta

    1981-04-30

    Experiments showed that the cumulation of technetium-99m following the administration of /sup 99m/Tc-Sn-pyrophosphate and s/sup 99m/Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum /sup 99m/Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of /sup 99m/Tc in the particular organs but also in the necrotic tissue of the myocardium.

  20. Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

    International Nuclear Information System (INIS)

    Vilcek, S.; Machan, V.; Kalincak, M.; Nicak, A.

    1981-01-01

    Experiments showed that the cumulation of technetium-99m following the administration of sup(99m)Tc-Sn-pyrophosphate and sup(99m)Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum sup(99m)Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of sup(99m)Tc in the particular organs but also in the necrotic tissue of the myocardium. (author)

  1. Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Renato A. K. Kalil

    2002-09-01

    Full Text Available OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg, in which 0.5 mL of saline solution (n=1 or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4 were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF instead of EGFP aims at developing gene therapy for ischemic heart disease.

  2. Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

    International Nuclear Information System (INIS)

    Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

    1982-01-01

    A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renogratin (to confirm the endocardial injection site) and radiolabeled colloid was injected in up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

  3. Handheld skin printer: in situ formation of planar biomaterials and tissues.

    Science.gov (United States)

    Hakimi, Navid; Cheng, Richard; Leng, Lian; Sotoudehfar, Mohammad; Ba, Phoenix Qing; Bakhtyar, Nazihah; Amini-Nik, Saeid; Jeschke, Marc G; Günther, Axel

    2018-05-15

    We present a handheld skin printer that enables the in situ formation of biomaterial and skin tissue sheets of different homogeneous and architected compositions. When manually positioned above a target surface, the compact instrument (weight <0.8 kg) conformally deposits a biomaterial or tissue sheet from a microfluidic cartridge. Consistent sheet formation is achieved by coordinating the flow rates at which bioink and cross-linker solution are delivered, with the speed at which a pair of rollers actively translate the cartridge along the surface. We demonstrate compatibility with dermal and epidermal cells embedded in ionically cross-linkable biomaterials (e.g., alginate), and enzymatically cross-linkable proteins (e.g., fibrin), as well as their mixtures with collagen type I and hyaluronic acid. Upon rapid crosslinking, biomaterial and skin cell-laden sheets of consistent thickness, width and composition were obtained. Sheets deposited onto horizontal, agarose-coated surfaces were used for physical and in vitro characterization. Proof-of-principle demonstrations for the in situ formation of biomaterial sheets in murine and porcine excisional wound models illustrate the capacity of depositing onto inclined and compliant wound surfaces that are subject to respiratory motion. We expect the presented work will enable the in situ delivery of a wide range of different cells, biomaterials, and tissue adhesives, as well as the in situ fabrication of spatially organized biomaterials, tissues, and biohybrid structures.

  4. The amount of viable and dyssynchronous myocardium is associated with response to cardiac resynchronization therapy: initial clinical results using multiparametric ECG-gated [{sup 18}F]FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Lehner, Sebastian; Uebleis, Christopher; Haug, Alexander; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Schuessler, Franziska; Kaeaeb, Stefan; Estner, Heidi [University of Munich, Medical Department I, Munich (Germany); Van Kriekinge, Serge D.; Germano, Guido [UCLA, Cedars-Sinai Medical Center, Los Angeles and David Geffen School of Medicine, Los Angeles, CA (United States); Hacker, Marcus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Theraphy, Vienna (Austria)

    2013-12-15

    There is still a significant amount of patients who do not sufficiently respond to cardiac resynchronization therapy (CRT). Previous studies demonstrated that the amount of dyssynchronous myocardium was predictive of response to CRT. Otherwise, non-response is frequently associated with high amounts of scar tissue. The combination of these parameters might yield a more accurate prediction of response. We hypothesized that the probability of a CRT response increases with the presence of high amounts of ''viable and dyssynchronous'' myocardium. A total of 19 patients (17 male, 61 {+-} 10 years) underwent ECG-gated [{sup 18}F]fluorodeoxyglucose (FDG) myocardial positron emission tomography (PET) before CRT device implantation and were followed for 6 months. Response to CRT was defined as clinical improvement of at least one New York Heart Association (NYHA) class in combination with left ventricular (LV) ejection fraction (EF) improvement of >5 %. Twelve responders (71 %) and seven non-responders (29 %) were identified. For each patient bullseye maps of FDG uptake and phase analysis were calculated (QPS/QGS 2012, Cedars-Sinai, Los Angeles, CA, USA) and fused. Amounts of myocardium representing ''viable and synchronous'', ''scar and synchronous'', viable and dyssynchronous or ''scar and dyssynchronous'' myocardium were quantified by planimetric measurements of the fused bullseye maps. Responders by definition showed significant decrease in NYHA class and significant increase of LVEF. Furthermore, a significantly higher amount of viable and dyssynchronous myocardium was found as compared to non-responders (21 {+-} 13 % vs 6 {+-} 5 %; p < 0.05). Combined assessment of myocardial viability and LV dyssynchrony is feasible using multiparametric [{sup 18}F]FDG PET and could improve conventional response prediction criteria for CRT. (orig.)

  5. Effects of hydroxyl radical induced-Injury in atrial versus ventricular myocardium of dog and rabbit

    Directory of Open Access Journals (Sweden)

    Nitisha Hiranandani

    2010-09-01

    Full Text Available Aim: Despite the widespread use of ventricular tissue in the investigation involving hydroxyl-radical (OH* injury, one of the most potent mediators in ischemia-reperfusion injury, little is known about the impact on atrial myocardium. In this study we thus compared the OH*-induced injury response between atrial and right ventricular muscles from both rabbits and dogs under identical experimental conditions. Methods: Small, contracting ventricular and atrial rabbit and dog trabeculae were directly exposed to OH*, and contractile properties were examined and quantified. Results: A brief OH* exposure led to transient rigor like contracture with marked elevation of diastolic tension and depression of developed force. Although the injury response showed similarities between atrial and ventricular myocardium, there were significant differences as well. In rabbit atrial muscles, the development of the contracture and its peak was much faster as compared to ventricular muscles. Also, at the peak of contracture, both rabbit and dog atrial muscles show a lesser degree of contractile dysfunction. Conclusion: These results indicate that both atrial and ventricular muscles develop a rigor like contracture after acute OH*-induced injury, and atrial muscles showed a lesser degree of contractile dysfunction. Comparison of dog versus rabbit tissue shows that the response was similar in magnitude, but slower to develop in dog tissue.

  6. From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide

    International Nuclear Information System (INIS)

    Brodsky, Berta; Erlanger-Rosengarten, Avigail; Proscura, Elena; Shapira, Elena; Wormser, Uri

    2008-01-01

    The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naive guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis

  7. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    OpenAIRE

    Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

  8. Probing myocardium biomechanics using quantitative optical coherence elastography

    Science.gov (United States)

    Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

    2015-03-01

    We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

  9. Effect of ethanol and the catalase inhibitor aminotriazole on lipid peroxidation in the rat myocardium

    International Nuclear Information System (INIS)

    Panchenko, L.F.; Pirozhkov, S.V.; Popova, S.V.; Antonenkov, V.D.

    1987-01-01

    The authors study the effect of chronic administration of ethanol and aminotriazole on the level of lipid peroxidation in the ray myocardium. The action of natural and artificial antioxidants on alcohol-induced lipid peroxidation also was studied. To determine the level of chemiluminescence, 1 ml of a sample of nuclear free homogenate or of the total fraction of particles was introduced for radioactivity measurement. After incubation the spontaneous weak luminescence was measured

  10. Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

    Science.gov (United States)

    Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K

    2016-04-20

    Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

  11. Preventative and Therapeutic Probiotic Use in Allergic Skin Conditions: Experimental and Clinical Findings

    Science.gov (United States)

    Özdemir, Öner; Göksu Erol, Azize Yasemin

    2013-01-01

    Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host. The interest in probiotic preventative/therapeutic potential in allergic diseases stemmed from the fact that probiotics have been shown to improve intestinal dysbiosis and permeability and to reduce inflammatory cytokines in human and murine experimental models. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against allergy. Therefore, many studies have been recently designed to examine the efficacy of probiotics, but the literature on the allergic skin disorders is still very scarce. Here, our objective is to summarize and evaluate the available knowledge from randomized or nonrandomized controlled trials of probiotic use in allergic skin conditions. Clinical improvement especially in IgE-sensitized eczema and experimental models such as atopic dermatitis-like lesions (trinitrochlorobenzene and picryl chloride sensitizations) and allergic contact dermatitis (dinitrofluorobenzene sensitization) has been reported. Although there is a very promising evidence to recommend the addition of probiotics into foods, probiotics do not have a proven role in the prevention or the therapy of allergic skin disorders. Thus, being aware of possible measures, such as probiotics use, to prevent/heal atopic diseases is essential for the practicing allergy specialist. PMID:24078929

  12. Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis.

    Science.gov (United States)

    Laggner, Ute; Di Meglio, Paola; Perera, Gayathri K; Hundhausen, Christian; Lacy, Katie E; Ali, Niwa; Smith, Catherine H; Hayday, Adrian C; Nickoloff, Brian J; Nestle, Frank O

    2011-09-01

    γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF-α- and IFN-γ-dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, these data indicate redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.

  13. Anti-Melanogenic Property of Geoditin A in Murine B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Chun-Tao Che

    2012-02-01

    Full Text Available Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and human colon HT29 cancer cells through an oxidative stress, a process also interfering with normal melanogenesis in pigment cells. Treatment of murine melanoma B16 cells with geoditin A decreased expression of melanogenic proteins and cell melanogenesis which was aggravated with adenylate cyclase inhibitor SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent signaling pathway. Immunofluorescence microscopy and glycosylation studies revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and tyrosinase-related protein 1, and a co-localization of tyrosinase with calnexin (CNX and lysosome-associated membrane protein 1 (LAMP-1, implicating a post-translational modification in the ER and a degradation of tyrosinase in the lysosome. Taken together, potent anti-melanogenic property and the relatively low cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin lightening agent.

  14. Stereological Cell Morphometry In Right Atrium Myocardium Of Primates

    Science.gov (United States)

    Mandarim-De-Lacerda, Carlos A...; Hureau, Jacques

    1986-07-01

    The mechanism by which the cardiac impulse is propagated in normal hearts from its origin in the sinus node to the atrio-ventricular node has not been agreed on fully. We studied the "internodal posterior tract" through the crista terminalis by light microscopy and stereological morphometry. The hearts of 12 Papio cynocephalus were perfused , after sacrifice,with phosphate-buffered formol saline. The regions of the crista terminalis (CT), interatrial septum (IAS), atrioventricular bundle (AVB) and interventricular septum (IVS) were cut off and embedded in paraplast and sectioned (10 4m). The multipurpose test system M 42 was superimposed over the photomicrographs (1,890 points test, ESR = 2%) to the stereological computing. The quantitative results show that the cells from CT were more closely relationed with IAS cells than others cells (IVS and AVB cells). This results are not a morphological evidence to establish the specificity of the "internodal posterior tract". The cellular arrangement and anatomical variation in CT myocardium is very important.

  15. Murine Models of Gastric Corpus PreneoplasiaSummary

    Directory of Open Access Journals (Sweden)

    Christine P. Petersen

    2017-01-01

    Full Text Available Intestinal-type gastric adenocarcinoma evolves in a field of pre-existing metaplasia. Over the past 20 years, a number of murine models have been developed to address aspects of the physiology and pathophysiology of metaplasia induction. Although none of these models has achieved true recapitulation of the induction of adenocarcinoma, they have led to important insights into the factors that influence the induction and progression of metaplasia. Here, we review the pathologic definitions relevant to alterations in gastric corpus lineages and classification of metaplasia by specific lineage markers. In addition, we review present murine models of the induction and progression of spasmolytic polypeptide (TFF2–expressing metaplasia, the predominant metaplastic lineage observed in murine models. These models provide a basis for the development of a broader understanding of the physiological and pathophysiological roles of metaplasia in the stomach. Keywords: SPEM, Intestinal Metaplasia, Gastric Cancer, TFF2, Chief Cell, Hyperplasia

  16. The influence of the perinatal chronic hyperglycaemia on the pattern of NOS isoforms expression in left ventricle myocardium in male rats of pre-pubertal age

    Directory of Open Access Journals (Sweden)

    O. V. Gancheva

    2016-12-01

    Full Text Available The aim of our study was to find out the features of the nitric oxide synthase (NOS isoforms expression in longitudinal and transversal layers of the myocardium of the left ventricle in male rats of 3 months, which are descendants of female rats with experimental gestational diabetes (EGD. Materials and methods. Study was carried out on 10 male rats descendants of female rats with normal course of pregnancy and 10 descendants of female rats with EGD. We evaluated the expression of neuronal, endothelial and inducible isoforms of NOS in histological sections both of transversal and longitudinal layers of the myocardium of left ventricle. With the aim to analyze the pattern of the NOS isoforms expression in 5 um histological slices of left ventricle myocardium we have carried out a complex of histochemical assays. Slices were allocated to 3 groups: 1st one was incubated with rabbit IgG to neuronal NOS (Santa Cruz Biotechnology, USA in dilution of 1:200; 2nd group underwent the incubation with rabbit IgG to endothelial NOS (eNos (Santa Cruz Biotechnology, USA in dilution 1:200; 3rd group was incubated with mice IgG to inducible NOS (iNos conjugated with FITC (Santa Cruz Biotechnology, USA in dilution of 1:200. The analysis of images was carried out with VIDAS-2.5 application package (Kontron Elektronik, Germany. Microimages of the left ventricle myocardium obtained with AxioScope (Carl Zeiss, Germany and COHU 4922 (COHU Inc., USA camera were processed in the system of digital image analysis VIDAS-386 (Kontron Elektronik, Germany. Results. In the study we have found that prenatal hyperglycaemia leads to the significant changes of the expression of NOS isoforms in the myocardium of left ventricle in male rats descendants of females with EGD, and the contain and the allocation of these enzymes are dependent both on type of the enzyme and its location in muscular layers. For eNOS the increase of the expression and the allocation in both transversal and

  17. Isolated noncompaction of myocardium associated with calcification in the interventricular septum.

    Science.gov (United States)

    Nil, M; Mori, K; Yuasa, Y; Ichida, F

    2003-01-01

    We describe a 12-year-old male with isolated noncompaction of the myocardium and associated abnormal calcification in the basal interventricular septum, and we present a review of the literature. The patient has been healthy and free of symptoms. The electrocardiogram showed abnormal Q waves in III, V1, V2, and ST elevation in V1-V3. Exercise testing demonstrated ST depression in V4 and V5. Myocardial scintigraphic examination showed a regional reduction in iodine-1,2,3-beta-methyl-iodophenylpentadecanoic acid uptake in the basal interventricular septum. Since coronary angiography demonstrated normal coronary vessels and the trabeculations were not prominent in this region, we hypothesize that coronary microcirculatory dysfunction may cause subendocardial infarction associated with calcification in the same area.

  18. Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

    Directory of Open Access Journals (Sweden)

    Gurjot Basra

    2012-01-01

    Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

  19. Method for radio imaging the myocardium of mammals using radio-labelled lipophil cations

    International Nuclear Information System (INIS)

    1984-01-01

    The invention relates to a method for the radio imaging of myocardia of mammals by concentrating a radiolabelled cation in myocardial tissue and by producing a radiograph using imaging techniques. According to the invention, it is found that a group of substances shows a preference to myocardial tissues upon intravenous injection in mammals. The characteristic of the invention is that radiolabelled quaternary ammonium, quaternary phosphorous or quaternary arsenic compounds with at least two aryl groups are intravenously injected. These substances provide a sufficiently high radioactivity giving an approved diagnostic image of the myocardium. (G.J.P.)

  20. Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability : A PET study

    NARCIS (Netherlands)

    Slart, Riemer H. J. A.; Agool, Ali; van Veldhuisen, Dirk J.; Dierckx, Rudi A.; Bax, Jeroen J.

    SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on

  1. Identification of a novel pro-inflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis

    Science.gov (United States)

    LAGGNER, Ute; DI MEGLIO, Paola; PERERA, Gayathri K.; HUNDHAUSEN, Christian; LACY, Katie E.; ALI, Niwa; SMITH, Catherine H.; HAYDAY, Adrian C.; NICKOLOFF, Brian J.; NESTLE, Frank O.

    2011-01-01

    γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is poorly characterized. In this study we show in vivo evidence that human blood contains a distinct subset of pro-inflammatory cutaneous lymphocyte antigen (CLA) and C-C chemokine receptor (CCR) 6 positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of pro-inflammatory mediators including IL-17A and activated keratinocytes in a TNF-α and IFN-γ dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared to healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, this data indicates redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human pro-inflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. PMID:21813772

  2. Detection and partial characterization of a midlamina lucida-hemidesmosome-associated antigen (19-DEJ-1) present within human skin

    DEFF Research Database (Denmark)

    Fine, J D; Horiguchi, Y; Jester, J

    1989-01-01

    , esophagus, cervix, and cornea, and BMs surrounding smooth muscle in medium-sized vessels, placenta, uterus, and esophagus. When 16 human fetal skins (aged 54-142 gestational days) were examined, the antigen was first detected at 81 days. Using immunoperoxidase and immunogold staining techniques, indirect......A murine anti-human monoclonal antibody (19-DEJ-1) has been produced that binds to basement membranes (BMs) of the dermoepidermal junction and arrector pili muscles but not to either dermal glandular or vascular BMs. 19-DEJ-1 also recognizes BMs underneath epithelia of buccal mucosa, tongue......-specific proteoglycan that is present within BMs along the epithelial-connective tissue interface and around smooth muscle in skin and other selected organs. Its unique ultrastructural localization suggests the possibility that 19-DEJ-1 may recognize an antigenic epitope of either anchoring filaments or alternatively...

  3. Quantitative stress-redistribution planar T1-201 scintigraphy: Assessment of the extent of hypoperfused myocardium by relationship to angiographic findings

    International Nuclear Information System (INIS)

    Bassir, R.; Maddahi, J.; Garcia, E.

    1984-01-01

    The size of hypoperfused myocardium (HM) in coronary artery (CA) disease (D) potentially provides a prognostic index that may not be accurately assess by conventional angiographic classification. The authors studied 62 consecutive patients (pts) with planar stress-redistribution T1-201 scintigraphy (T1-201) and coronary arteriography who did not have prior myocardial infarction and achieved 85% predicted maximum heart rate on exercise. Of 62 pts, 42 had CAD (>50% stenosis). For T1-201 quantification of the size of HM, maximum count circumferential profiles of initial distribution and % washout were obtained and compared to previously established normal limits. The area enclosed between the normal limits and the abnormal portion of the pt's profiles represented a quantitative T1-201 jeopardy score (JS). Despite increasing T1-201 JS from 1 to 3 vessel (V) and left-main (LM) D, significant overlap between the different angiographic groups was observed; of 45 pts with mild JS (<300), 14 (31%) had 3VD and/or LMD. The angiographic extent of CAD was also analyzed using a method (CLASS) proposed by Gensini et al based on the CA territory, location and severity of stenosis, and collateral circulation. T1-201 JS correlated significantly with CLASS (r=.78, p<.01). Of the 45 pts with mild JS, only 5 (11%) had severe CLASS score. Thus, the size of the hypoperfused myocardium by quantitative stress- and redistribution T1-201 correlates better with a more complex angiographic estimate of myocardium at risk than conventional 1, 2, and 3 vessel disease classification

  4. Study on the kinetics of high-energy phosphates in myocardium by phosphorous nuclear magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Kusuoka, Hideo; Tsuneoka, Yutaka; Inoue, Michitoshi; Abe, Hiroshi [Osaka Univ. (Japan). Faculty of Medicine; Watari, Hiroshi

    1982-12-01

    Effect of artificial blood, FC 43 (Perfluorochemicals) on the kinetics of high-energy phosphate in the myocardium was evaluated by /sup 31/P-NMR which permits a continuous and non-invasive assessment of in vivo phosphorus compounds. Cardiac perfusion was carried out on a excised rat heart with a Krebs-Henseleit modified solution and FC 43 alternately. Under the normal condition, ischemic condition, and at second perfusion amounts of intramyocardial creatine phosphoric acid, ATP, and inorganic phosphorus were determined by /sup 31/P-NMR. Coronary flow was simultaneously estimated. The ischemic state due to interruption of perfusion resulted in a decrease in creatine phosphoric acid, which was associated with an increase in inorganic phosphorus and intracellular acidosis. No change of ATP amount was observed under ischemic state. With resumption of perfusion, the levels of creatine phosphoric acid and inorganic phosphorus rapidly returned to the normal. In the group of FC 43, coronary flow was 2.68 ml/min/g of the heart weight, about 1/2 of that of the Krebs-Henseleit group (5.68 ml/min/g of the heart weight). In controls, there was no difference between the two groups concerning creatine phosphoric acid level and recovery of creatine phospohric acid level after ischemia. These results showed that FC 43 supplies sufficient oxygen, and has no effect on the kinetics of energy in the myocardium.

  5. Biophysical foundations for the study of the electrical excitability and action potential propagation in myocardium

    International Nuclear Information System (INIS)

    Suarez Antola, R.

    1991-01-01

    The electric current flow in the heterogeneous and anysotropic volume conductor of the myocardium is studied. The equations of bidomain theory are derived using an approach framed in the theory of averaged fields, introducing microscopic, mesoscopic and macroscopic spatial scales. However, the procedure, compatible with the histological and the anatomical details of the organ, is different from the multiple scale asymptotic expansions usually applied in homogeneization problems. A probabilistic approach framed in large numbers theorems is used to derive the equation for membrane ionic current from the stochastic activity of the channels at the microscopic level. An operational procedure suitable to define a sharp bidomain boundary from the fuzzy distribution of structural details and physical properties at the histological level is given. The problem of threshold is studied. The sizes and shapes of critical masses of cardiac cells that must be depolarized above threshold in order to produce a propagated action potential are determined by an approximate analytical procedure. The concept of family of threshold patterns for the emergence of action potentials in the heart is introduced. This concept is applied to discuss the conditions of emergence of ectopic focus. Analytical formulae are derived, for the time constant and the rheobase for electrical stimulation of the myocardium. These formulae are in good agreement with known experimental results. New experiments that could be done to confirm or reject them are suggested

  6. Intrinsic washout rates of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation

    International Nuclear Information System (INIS)

    Beller, G.A.; Holzgrefe, H.H.; Watson, D.D.

    1985-01-01

    Infusion of dipyridamole has been suggested as an alternative to exercise stress for myocardial perfusion imaging for detection of ischemia, but the mechanism and significance of thallium-201 ( 201 Tl) redistribution after administration of dipyridamole are uncertain. If disparate intrinsic cellular efflux rates of 201 Tl from normal and relatively underperfused myocardium in response to dipyridamole-induced vasodilation were observed, this could explain delayed 201 Tl redistribution. We investigated the effect of an intravenous infusion of 0.15 mg/kg dipyridamole on the intrinsic myocardial washout rate of 201 Tl as measured with a gamma-detector probe after intracoronary injection (50 muCi) of the radionuclide in open-chested anesthetized dogs. In six normal dogs the t 1/2 for intrinsic 201 Tl washout from the myocardium was 89 +/- 11 min (SE) at control conditions and became more rapid at 59 +/- 10 min (p . .0001) after dipyridamole. This corresponded to a significant increase in microsphere-determined epicardial (0.95 +/- 0.11 to 2.23 +/- 0.46 ml/min/g; p . .01) and endocardial (0.86 +/- 0.10 to 1.53 +/- 0.27; p . .029) flows. In 12 dogs with a critical coronary stenosis, the 201 Tl intrinsic washout rate slowed from 70 +/- 5 to 104 +/- 6 min (p . .0001) after production of the stenosis and slowed even further to 169 +/- 21 min (p . .003) after dipyridamole

  7. Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

    International Nuclear Information System (INIS)

    Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

    1982-01-01

    A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of radiocolloids. For injection of the left ventricle, the catheter is introduced through the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renografin (to confirm the endocardial injection site) and radiolabeled colloid was injected in 13 animals. Ten minutes after injection, scintigraphy was begun and continued for up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

  8. Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET

    International Nuclear Information System (INIS)

    Yoshinaga, Keiichiro; Tamaki, Nagara; Katoh, Chietsugu; Kuge, Yuji; Noriyasu, Kazuyuki; Yamada, Satoshi; Ito, Yoshinori; Kohya, Tetsuro; Kitabatake, Akira; Kawai, Yuko

    2002-01-01

    The detection of viable myocardium is important for the prediction of functional recovery after revascularisation. However, a fixed perfusion defect often includes viable myocardium, and perfusion imaging then underestimates myocardial viability. We previously reported that low-dose dobutamine stress gated single-photon emission tomography (SPET) provides similar findings to dobutamine stress echocardiography in the assessment of myocardial viability. The present study investigated whether low-dose dobutamine stress gated SPET is of additional value as compared with stress-rest technetium-99m tetrofosmin SPET for the detection of myocardial viability. Standard stress-rest perfusion SPET, low-dose dobutamine stress gated SPET and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) were studied in 23 patients (mean age 67±7.6 years) with previous myocardial infarction. Twenty-one of them were successfully studied with each technique. FDG PET viability (FDG uptake ≥50%) was employed as the gold standard. One-day stress-rest 99m Tc-tetrofosmin myocardial SPET was performed. After the resting study, gated SPET was acquired following infusion of 7.5 μg kg -1 min -1 of dobutamine. Left ventricular wall motion in 16 segments was assessed by cine mode display using a four-point scale. Myocardial viability was considered present when there was improvement by one point. Of a total of 336 segments analysed, 53 had persistent defects on stress-rest perfusion SPET. FDG viability was seen in 16 of 17 dobutamine-responsive segments, but in only 11 of 36 dobutamine non-responsive segments (P<0.01). Thus, in the segments with persistent defects, viability findings on low-dose dobutamine stress gated SPET were concordant with those on FDG PET in 77% of segments (kappa value =0.55). For the detection of FDG-viable myocardium, the combination of stress-rest perfusion SPET and low-dose dobutamine stress gated SPET achieved a better sensitivity than stress

  9. Differentiation of recently infarcted myocardium from chronic myocardial scar: the value of contrast-enhanced SSFP-based cine MR imaging

    International Nuclear Information System (INIS)

    Kim, Kyoung Ah; Seo, Joon Beom; Do, Kyoung Hyun; Heo, Jeong Nam; Lee, Young Kyung; Song, Jae Woo; Lee, Jin Seong; Song, Koun Sik; Lim, Tae Hwan

    2006-01-01

    The purpose of this study is to demonstrate whether the signal intensity (SI) of myocardial infarction (MI) on contrast enhanced (CE)-cine MRI is useful for differentiating recently infarcted myocardium from chronic scar. This study included 24 patients with acute MI (36-84) years, mean age: 57) and 19 patients with chronic MI (44-80) years, mean age: 64). The diagnosis of acute MI was based on the presence of typical symptoms, i.e. elevation of the cardiac enzymes and the absence of any remote infarction history. The diagnosis of chronic MI was based on a history of MI or coronary artery disease of more than one month duration and on the absence of any recent MI within the previous six months. Retrospectively, the ECG-gated breath-hold cine imaging was performed in the short axis plane using a segmented, balanced, turbo-field, echo-pulse sequence two minutes after the administration of Gd-DTPA at a dose of 0.2 mmol/kg body weight. Delayed contrast-enhanced MRI (DCE MRI) in the same plane was performed 10 to 15 minutes after contrast administration, and this was served as the gold standard of reference. The SI of the infarcted myocardium on the CE-cine MRI was compared with that of the normal myocardium on the same image. The area of abnormal SI on the CE-cine MRI was compared with the area of hyper enhancement on the DCE MRI. The area of high SI on the CE-cine MRI was detected in 23 of 24 patients with acute MI (10 with homogenous high SI, 13 high SI with subendocardial low SI, and one with iso SI). The area of high SI on the CE- cine MRI was larger than that seen on the DCE MRI (ρ < 0.05). In contrast, the areas of chronic MI were seen as iso-SI with thin subendocardial low SI on the CE-cine MR in all the chronic MI patients. The presence of high SI on both the CE-cine MRI and the DCE MRI is more sensitive (95.8%) for determining the age of a MI than the presence of myocardial thinning (66.7%). The study showed the different SI patterns between recently

  10. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

    1995-06-15

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

  11. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    International Nuclear Information System (INIS)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won; Park, Choong Ki

    1995-01-01

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly (ρ < 0.01) and azygos engorgement (ρ < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality

  12. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

    1995-06-15

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

  13. Analysis of cardiomyocyte movement in the developing murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  14. Comparison of exercise and pharmacologic stress in myocardium perfusion imaging for CHD

    International Nuclear Information System (INIS)

    Li Zebo; Zheng Kangni; Cheng Xiaorui; Liu Hui; Cheng Yihai

    1995-01-01

    In order to provide a proper stress test, exercise, dipyridamole and ATP stress were compared. Three modalities were compared with respect to the detecting rate, methodology, hemodynamic and side effects. There are no significant differences in their ability of detecting coronary heart disease (CHD) (P>0.05). Exercise stress causes an increase in heart rate, blood pressure and myocardium oxygen consumption. Pharmacologic stress cause a slight increase in heart rate, but a decrease in blood pressure (P<0.01). Exercise stress is a basic method with good image quality, but it needs a special equipment. Pharmacologic stress is an easier, cheaper and safer method, particularly useful for patients unable to perform exercise test

  15. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

    Science.gov (United States)

    Jung, Kyung-Hwa; Baek, Hyunjung; Kang, Manho; Kim, Namsik; Lee, Seung Young; Bae, Hyunsu

    2017-02-18

    Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  16. In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation.

    Science.gov (United States)

    Jatana, Samreen; Palmer, Brian C; Phelan, Sarah J; Gelein, Robert; DeLouise, Lisa A

    2017-04-14

    Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm 2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model. Results indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment. Our data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.

  17. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

  18. Application of a New Robust ECG T-Wave Delineation Algorithm for the Evaluation of the Autonomic Innervation of the Myocardium

    DEFF Research Database (Denmark)

    Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

    2016-01-01

    T-wave amplitude (TWA) is a well know index of the autonomic innervation of the myocardium. However, until now it has been evaluated only manually or with simple and inefficient algorithms. In this paper, we developed a new robust single-lead electrocardiogram (ECG) T-wave delineation algorithm...

  19. Discrimination of skin sensitizers from non-sensitizers by interleukin-1α and interleukin-6 production on cultured human keratinocytes.

    Science.gov (United States)

    Jung, Daun; Che, Jeong-Hwan; Lim, Kyung-Min; Chun, Young-Jin; Heo, Yong; Seok, Seung Hyeok

    2016-09-01

    In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non-sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non-sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin-1α (IL-1α) and IL-6 were measured. The sensitivity of IL-1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL-6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro-inflammatory cytokines IL-1α and IL-6 by human HaCaT cells may potentially classify skin sensitizers from non-sensitizers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Experimental study of 31P MR spectroscopy in vitro canine myocardium

    International Nuclear Information System (INIS)

    Gao Fabao; Zhao Haitao; Suo Liping; Zhang Yushun; Fang Hong; Huang Zhilan

    1999-01-01

    Objective: To conduct a dynamic survey of the metabolism of high-energy phosphates in myocardium in order to define, the relationship between the changes in myocardial energy metabolism and the duration of ischemia. Methods: A dynamic survey of isolated heart of 8 dogs was done with the use of 31 P MRS. Results: Myocardial PCr level decreased rapidly after the heart was isolated and was reduced to zero in 2-3 hours. ATP level diminished progressively to its depletion at 6 hours following isolation. Conclusions: After the heart was isolated, the PCr level rapidly decreased and was reduced to zero in 2-3 hours whereas ATP was not depleted until 4-6 hours after isolation. The ATP level remained within normal limits as long as PCr had not been depleted

  1. Radionuclide imaging in primary and secondary disorders of the myocardium

    International Nuclear Information System (INIS)

    Follansbee, W.P.

    1987-01-01

    The list of all potential causes of myocardial disease or injury is an extensive one: a condensed version is presented. Conceptually these processes can be categorized into those which are, or appear to be, primary to the myocardium and those which secondarily involve it. Nuclear imaging procedures, particularly those used to assess ventricular function, are in a general sense potentially applicable to the clinical evaluation of any of these entities. In certain of these conditions, however, nuclear cardiac procedures have a demonstrated or potential additional and more specific role for the diagnosis and quantification of the entity. A number of these, including coronary artery disease, valvular heart disease, cor pulmonale, and myocardial trauma, are the topics of other chapters and, therefore, are not dealt with further here. The remainder of the myocardial disorders in which nuclear imaging procedures have a recognized or potential specific role are the focus of this discussion

  2. Effect of the lectin of Bauhinia variegata and its recombinant isoform on surgically induced skin wounds in a murine model.

    Science.gov (United States)

    Neto, Luiz Gonzaga do Nascimento; Pinto, Luciano da Silva; Bastos, Rafaela Mesquita; Evaristo, Francisco Flávio Vasconcelos; Vasconcelos, Mayron Alves de; Carneiro, Victor Alves; Arruda, Francisco Vassiliepe Sousa; Porto, Ana Lúcia Figueiredo; Leal, Rodrigo Bainy; Júnior, Valdemiro Amaro da Silva; Cavada, Benildo Sousa; Teixeira, Edson Holanda

    2011-11-07

    Lectins are a structurally heterogeneous group of highly specific carbohydrate-binding proteins. Due to their great biotechnological potential, lectins are widely used in biomedical research. The purpose of the present study was to evaluate the healing potential of the lectin of Bauhinia variegata (nBVL) and its recombinant isoform (rBVL-1). Following surgical creation of dorsal skin wounds, seven groups of mice were submitted to topical treatment for 12 days with lectin, D-galactose, BSA and saline. The animals were anesthetized and euthanized on POD 2, 7 and 12 in order to evaluate the healing potential of each treatment. The parameters considered included wound size, contraction rate, epithelialization rate and histopathological findings. Wound closure was fastest in animals treated with rBVL-1 (POD 7). nBVL was more effective than the controls. All skin layers were reconstructed and keratin deposition increased. Our findings indicate that the lectin of Bauhinia variegata possesses pro-healing properties and may be employed in the treatment of acute skin wounds.

  3. A coupled 3D-1D numerical monodomain solver for cardiac electrical activation in the myocardium with detailed Purkinje network

    Science.gov (United States)

    Vergara, Christian; Lange, Matthias; Palamara, Simone; Lassila, Toni; Frangi, Alejandro F.; Quarteroni, Alfio

    2016-03-01

    We present a model for the electrophysiology in the heart to handle the electrical propagation through the Purkinje system and in the myocardium, with two-way coupling at the Purkinje-muscle junctions. In both the subproblems the monodomain model is considered, whereas at the junctions a resistor element is included that induces an orthodromic propagation delay from the Purkinje network towards the heart muscle. We prove a sufficient condition for convergence of a fixed-point iterative algorithm to the numerical solution of the coupled problem. Numerical comparison of activation patterns is made with two different combinations of models for the coupled Purkinje network/myocardium system, the eikonal/eikonal and the monodomain/monodomain models. Test cases are investigated for both physiological and pathological activation of a model left ventricle. Finally, we prove the reliability of the monodomain/monodomain coupling on a realistic scenario. Our results underlie the importance of using physiologically realistic Purkinje-trees with propagation solved using the monodomain model for simulating cardiac activation.

  4. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical–Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2015-04-15

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin

  5. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    International Nuclear Information System (INIS)

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R 2 = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q 2 ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin sensitization and

  6. Prediction of skin sensitization potency using machine learning approaches.

    Science.gov (United States)

    Zang, Qingda; Paris, Michael; Lehmann, David M; Bell, Shannon; Kleinstreuer, Nicole; Allen, David; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Strickland, Judy

    2017-07-01

    The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non-sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non-animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave-one-out cross-validation. A one-tiered strategy modeled all three categories of response together while a two-tiered strategy modeled sensitizer/non-sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two-tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one-tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non-animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Effects of Cordyceps sinensis on the Expressions of NF-κB and TGF-β1 in Myocardium of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    You-you Gu

    2015-01-01

    Full Text Available Objective. To investigate the effect of Cordyceps sinensis (CS on the expressions of NF-κB and TGF-β1 in myocardium of streptozotocin-induced diabetic rats. Methods. A total of 53 healthy male SD rats, mice age of 8 weeks and weight of 220 ± 20 g, were randomly divided into five groups by randomized block design: normal control group (n=10, diabetic group (n=10, low dose of CS group (n=12; CS 0.6 g·kg−1·d−1, middle dose of CS group (n=11; CS 2.5 g·kg−1·d−1, and high dose of CS group (n=10; CS 5 g·kg−1·d−1. The diabetic models with tail intravenous injection by streptozotocin (45 mg·kg−1. Diabetic rats were sacrificed after 8 weeks; the expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle were determined by using immunohistochemistry staining and reverse transcription polymerase chain reaction (RT-PCR method. The data were analyzed using one factor analysis of variance. Result. The expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle of diabetic rats were significantly raised (P<0.05, which could be decreased by CS (P<0.05. Conclusions. The changes on the expressions of NF-κB and TGF-β1 in myocardium may be involved in the occurrence of diabetic cardiomyopathy (DC. CS may play its role on myocardial protection by regulating the expressions of NF-κB and TGF-β1 in myocardium.

  8. [Effect of medicines for activating blood and reinforcing Qi on angiogenesis in infarcted myocardium edge area of acute myocardial infarction model in rats].

    Science.gov (United States)

    Zang, Wen-Hua; Yin, Shen-Hua; Tang, De-Cai; Li, Bing-Bing

    2014-03-01

    To study the effect of medicines for activating blood and reinforcing Qi on the number of new micro-vessels and the protein expressions of VEGF and bFGF in the infarcted myocardium edge area of acute myocardial infarction (AMI) model in rats. The AMI model of rats was established. After the successful model establishment, rats were randomly divided into the sham-operated group, the model group, the Danshen-Huangqi (1 : 2) group, the Danshen-Huangqi (1 : 1) group, the Chuanxiong-Huangqi (1 : 2) group, the Danshen group, the Chuanxiong group, the Chishao group and the Shexiang Baoxin pill group, with five rats in each group. Rats in each medicated group were orally administered with drugs as per 13.5 g x kg(-1) x d(-1) once everyday for three weeks. The immunohistochemical SP method was adopted to detect the expression of vWF in myocardial tissues, and count the number of micro-vessels (MVC). The protein expression of VEGF and bFGF in myocardial tissues were determined by Western blot. The new micro-vessels stained by vWF factor could be found in the infarcted myocardium edge area of the sham-operated group, the model group and all of medicated groups. The sham-operated group show unobvious new micro-vessels in myocardial tissues. A small amount of new micro-vessels could be seen in the infarcted myocardium edge area of the model group. Whereas a larger number of micro-vessels could be seen in the infarcted myocardium edge area of all of medicated groups. The differences between the sham-operated group and the model group had statistical significance (P effect in promoting angiogenesis. Their mechanism for promoting angiogenesis may be related to the improvement of the protein expressions of VEGF and bFGF, so as to increase the contents of VEGF and bFGF and promote the angiogenesis of new vessels.

  9. Efficacy of topical and systemic antibiotic treatment of meticillin-resistant Staphylococcus aureus in a murine superficial skin wound infection model

    DEFF Research Database (Denmark)

    Vingsbo Lundberg, Carina; Frimodt-Møller, Niels

    2013-01-01

    Meticillin-resistant Staphylococcus aureus (MRSA) is a rapidly spreading pathogen associated predominantly with skin infections. The lack of clinical evidence indicating the best treatment strategy to combat MRSA skin infections prompted us to investigate the efficacy of available treatment options...... were determined. Retapamulin, fusidic acid and mupirocin treatment for 3 days reduced the bacterial loads by 2.5, 2.9 and 2.0 log(10) CFU, respectively, and treatment for 6 days by 5.0, 4.2 and 5.1 log(10) CFU, respectively, compared with non-treated controls (P...

  10. Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease

    International Nuclear Information System (INIS)

    Pace, L.; Cuocolo, A.; Salvatore, M.; Perrone-Filardi, P.; Prastaro, M.; Vezzuto, P.; Crisci, T.; Dellegrottaglie, S.; Piscione, F.; Chiariello, M.; Mainenti, P.P.; Varrone, A.

    1998-01-01

    The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201 Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201 Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40±20) after myocardial revascularization. Discriminant analysis was applied to the results of 201 Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201 Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P 201 Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined. (orig.)

  11. Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4+ T Cells That Are Functionally Suppressive.

    Directory of Open Access Journals (Sweden)

    David E Sanin

    2015-05-01

    Full Text Available The skin provides an important first line of defence and immunological barrier to invasive pathogens, but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms. In schistosomiasis-endemic regions, populations can experience repeated percutaneous exposure to schistosome larvae, however little is known about how repeated exposure to pathogens affects immune regulation in the skin. Here, using a murine model of repeated infection with Schistosoma mansoni larvae, we show that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. Whilst CD4+ T cells are the primary cellular source of regulatory IL-10, they expressed none of the markers conventionally associated with T regulatory (Treg cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b. Nevertheless, these IL-10+ CD4+ T cells in the skin from repeatedly infected mice are functionally suppressive as they reduced proliferation of responsive CD4+ T cells from the skin draining lymph node. Moreover, the skin of infected Rag-/- mice had impaired IL-10 production and increased neutrophil recruitment. Finally, we show that the mechanism behind IL-10 production by CD4+ T cells in the skin is due to a combination of an initial (day 1 response specific to skin commensal bacteria, and then over the following days schistosome-specific CD4+ T cell responses, which together contribute towards limiting inflammation and tissue damage following schistosome infection. We propose CD4+ T cells in the skin that do not express markers of conventional T regulatory cell populations have a significant role in immune regulation after repeated pathogen exposure and speculate that these cells may also help to maintain skin barrier function in the context of repeated percutaneous insult by other skin pathogens.

  12. Skin graft

    Science.gov (United States)

    Skin transplant; Skin autografting; FTSG; STSG; Split thickness skin graft; Full thickness skin graft ... donor site. Most people who are having a skin graft have a split-thickness skin graft. This takes ...

  13. Myocardium scintigraphy and coronaries scanner: results and respective contribution of these two examinations; Scintigraphie myocardique et scanner coronaire: resultats et apport respectif des deux examens

    Energy Technology Data Exchange (ETDEWEB)

    Songy, B.; Balestrini, V.; Sablayrolles, J.L.; Vigoni, F.; Lussato, D. [Centre cardiologique du Nord (CCN), Saint-Denis, (France); Faccio, F. [fondation San Geronimo, Santa Fe, (Argentina)

    2009-05-15

    The objective were to evaluate the results and the respective contribution of the myocardium scintigraphy and the coro-scanner. It exists an excellent correlation between a normal scanner and a normal scintigraphy (97%). 30% of patients having non tight stenosis at scanner and 60% of these ones having tight stenosis have a scintigraphy ischemia; An abnormal scanner, whatever be the the degree of stenosis must be completed by a test of myocardium ischemia. The actual limitations of the coro-scanner (64 gills) are in relation with its spatial resolution (quantification) and temporal resolution (right coronary). The choice of the diagnosis examination to realize in first intention must depend on the age and prevalence of the coronary disease. (N.C.)

  14. New perspectives in the treatment of damaged myocardium using autologous skeletal myoblasts

    International Nuclear Information System (INIS)

    Rigatelli, Gianluca; Rossini, Katia; Vindigni, Vincenzo; Mazzoleni, Francesco; Rigatelli, Giorgio; Carraro, Ugo

    2004-01-01

    Autologous skeletal myoblast transplantation may be used to ameliorate the healing process following myocardium infarct and, hopefully, cardiomyopathies. Despite successful animal experimentation, several issues need to be addressed in clinical settings, i.e., the impact of the delivery route, the extent of short- and long-term survival, and differentiation of the injected skeletal myoblasts. The authors offer some new hypotheses resulting from basic research, i.e., where and when to inject the myogenic cells, whatever their source, how to decrease new myofiber atrophy and improve their regeneration. Although these new hypotheses still need to be tested in humans, they may be decisive for future experimental studies and will lead to making endovascular cell implantation a more effective way to treat ischemic heart disease and failure

  15. Review of Natural Compounds for Potential Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tawona N. Chinembiri

    2014-08-01

    Full Text Available Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.

  16. Skin Diseases: Cross-section of human skin

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  17. Effect of the Lectin of Bauhinia variegata and Its Recombinant Isoform on Surgically Induced Skin Wounds in a Murine Model

    Directory of Open Access Journals (Sweden)

    Rodrigo Bainy Leal

    2011-11-01

    Full Text Available Lectins are a structurally heterogeneous group of highly specific carbohydrate-binding proteins. Due to their great biotechnological potential, lectins are widely used in biomedical research. The purpose of the present study was to evaluate the healing potential of the lectin of Bauhinia variegata (nBVL and its recombinant isoform (rBVL-1. Following surgical creation of dorsal skin wounds, seven groups of mice were submitted to topical treatment for 12 days with lectin, D-galactose, BSA and saline. The animals were anesthetized and euthanized on POD 2, 7 and 12 in order to evaluate the healing potential of each treatment. The parameters considered included wound size, contraction rate, epithelialization rate and histopathological findings. Wound closure was fastest in animals treated with rBVL-1 (POD 7. nBVL was more effective than the controls. All skin layers were reconstructed and keratin deposition increased. Our findings indicate that the lectin of Bauhinia variegata possesses pro-healing properties and may be employed in the treatment of acute skin wounds.

  18. A study on the kinetics of high-energy phosphates in myocardium by phosphorous nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Kusuoka, Hideo; Tsuneoka, Yutaka; Inoue, Michitoshi; Abe, Hiroshi; Watari, Hiroshi.

    1982-01-01

    Effect of artificial blood, FC 43 (Perfluorochemicals) on the kinetics of high-energy phosphate in the myocardium was evaluated by 31 P-NMR which permits a continuous and non-invasive assessment of in vivo phosphorus compounds. Cardiac perfusion was carried out on a excised rat heart with a Krebs-Henseleit modified solution and FC 43 alternately. Under the normal condition, ischemic condition, and at second perfusion amounts of intramyocardial creatine phosphoric acid, ATP, and inorganic phosphorus were determined by 31 P-NMR. Coronary flow was simultaneously estimated. The ischemic state due to interruption of perfusion resulted in a decrease in creatine phosphoric acid, which was associated with an increase in inorganic phosphorus and intracellular acidosis. No change of ATP amount was observed under ischemic state. With resumption of perfusion, the levels of creatine phosphoric acid and inorganic phosphorus rapidly returned to the normal. In the group of FC 43, coronary flow was 2.68 ml/min/g of the heart weight, about 1/2 of that of the Krebs-Henseleit group (5.68 ml/min/g of the heart weight). In controls, there was no difference between the two groups concerning creatine phosphoric acid level and recovery of creatine phospohric acid level after ischemia. These results showed that FC 43 supplies sufficient oxygen, and has no effect on the kinetics of energy in the myocardium. (Ueda, J.)

  19. Reproducibility of P-31 spectroscopic imaging of normal human myocardium

    International Nuclear Information System (INIS)

    Tavares, N.J.; Chew, W.; Auffermann, W.; Higgins, C.B.

    1988-01-01

    To assess reproducibility of P-31 MR spectroscopy of human myocardium, ten normal male volunteers were studied on two separate occasions. Spectra were acquired on a clinical 1.5-T MR imaging unit (Signa, General Electric) using a one-dimensional gated spectroscopic imaging sequence (matrix size, 32 X 256) over 20 minutes. Peaks in the adenosine triphosphate (ATP) region, phosphocreatine (PCR), phosphodiesters (PD), and peaks attributable to 2,3 diphosphoglycerate from blood were observed. Interindividual and intraindividual variability expressed as standard errors of the mean (mean +- SEM) were 1.54 +- 0.04 (variability among subjects) and 0.04 (variability between first and second studies) for PCR/β ATP; 0.97 +- 0.18 and 0.06 for PD/β ATP; and 0.62 +- 0.10 and 0.05 for PD/PCR, respectively. In conclusion, P-31 MR spectroscopy yields consistent and reproducible myocardial spectra that might be useful in the future for the evaluation and monitoring of cardiac disease

  20. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    Science.gov (United States)

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. PMID:25560673

  1. Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

    International Nuclear Information System (INIS)

    Spellman, C.W.; Beauchamp, D.A.

    1986-01-01

    Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

  2. Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

    Directory of Open Access Journals (Sweden)

    Amelia Kellar

    2015-01-01

    Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

  3. Spiritual and religious aspects of skin and skin disorders

    Directory of Open Access Journals (Sweden)

    Shenefelt PD

    2014-08-01

    Full Text Available Philip D Shenefelt,1 Debrah A Shenefelt2 1Dermatology and Cutaneous Surgery, University of South Florida, Tampa, 2Congregation Or Ahavah, Lutz, FL, USA Abstract: Skin and skin disorders have had spiritual aspects since ancient times. Skin, hair, and nails are visible to self and others, and touchable by self and others. The skin is a major sensory organ. Skin also expresses emotions detectable by others through pallor, coldness, "goose bumps", redness, warmth, or sweating. Spiritual and religious significances of skin are revealed through how much of the skin has been and continues to be covered with what types of coverings, scalp and beard hair cutting, shaving and styling, skin, nail, and hair coloring and decorating, tattooing, and intentional scarring of skin. Persons with visible skin disorders have often been stigmatized or even treated as outcasts. Shamans and other spiritual and religious healers have brought about healing of skin disorders through spiritual means. Spiritual and religious interactions with various skin disorders such as psoriasis, leprosy, and vitiligo are discussed. Religious aspects of skin and skin diseases are evaluated for several major religions, with a special focus on Judaism, both conventional and kabbalistic. Keywords: skin, skin disorders, spiritual, religious

  4. The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

    Science.gov (United States)

    Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

    2009-04-01

    The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.

  5. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2017-02-01

    Full Text Available Atopic dermatitis (AD is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg, and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  6. Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium.

    Science.gov (United States)

    Kanda, Pushpinder; Alarcon, Emilio I; Yeuchyk, Tanya; Parent, Sandrine; de Kemp, Robert A; Variola, Fabio; Courtman, David; Stewart, Duncan J; Davis, Darryl R

    2018-04-20

    Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.

  7. Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

    Science.gov (United States)

    Takeuchi, Koh; Minakawa, M; Otaki, M; Odagiri, S; Itoh, K; Murakami, A; Yaku, H; Kitamura, N

    2003-12-01

    Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

  8. Evaluation of noncoronary sources of left ventricular perfusion to intercoronary collateral-dependent myocardium due to chronic major vessel occlusion: absent contribution of luminal and extracardiac channels

    International Nuclear Information System (INIS)

    Crystal, G.J.; Downey, H.F.; Bashour, F.A.

    1981-01-01

    Liminal contribution to perfusion of collateral-dependent left ventricular (LV) myocardium was evaluated in six dogs. A portion of LV free wall was rendered collateral-dependent by gradual occlusion of left circumflex artery with Ameroid constrictor. Eight to 10 weeks after implantation of constrictor, measurements of LV myocardial flow were made by left atrial injections of 9-10 micro radioactive microspheres. To measure total collateral flow, microspheres were injected under control conditions, and to measure luminal contribution to collateral flow, microspheres were injected after ligation of right coronary artery during extracorporeal perfusion of left common coronary artery (LCCA) with microsphere-free arterial blood, and during stoppage of flow through LCCA. Under control conditions, myocardial blood flow in collateral-dependent region, 1.01 +/- 0.31 ml/min/gm, was not significantly different from that in normal region, 1.06 +/- 0.32 ml/min/gm. Flow from luminal collateral vessels was negligible (less than 0.005 ml/min/gm) in both collateral-dependent and normal myocardium, and was not affected by stoppage of flow through LCCA. These results indicate that luminal collateral vessels, as well as collateral vessels originating from other noncoronary sources, do not contribute significantly to perfusion of normal or collateral-dependent LV myocardium

  9. Adaptation of the cardiovascular system to postinfarction cardiosclerosis in rats with congenital adrenoreactivity of the myocardium.

    Science.gov (United States)

    Usacheva, M A; Popkova, E V; Smirnova, E A; Saltykova, V A; Belkina, L M

    2007-12-01

    Three months after myocardial infarction the severity of heart failure and size of postinfarction scars in August rats with inherently reduced adrenoreactivity of the myocardium were similar to those in Wistar rats. The mortality rate in August rats was 2.5-fold lower than in Wistar rats. During the postinfarction period, myocardial adrenoreactivity in August rats remained lower, while the efficiency of cardiac function was 62% higher than in Wistar rats. The incidence of epinephrine-induced arrhythmias in August rats was much lower than in Wistar rats.

  10. Skin tightening.

    Science.gov (United States)

    Woolery-Lloyd, Heather; Kammer, Jenna N

    2011-01-01

    Skin tightening describes the treatment of skin laxity via radiofrequency (RF), ultrasound, or light-based devices. Skin laxity on the face is manifested by progressive loss of skin elasticity, loosening of the connective tissue framework, and deepening of skin folds. This results in prominence of submandibular and submental tissues. Genetic factors (chronological aging) and extrinsic factors (ultraviolet radiation) both contribute to skin laxity. There are many RF, ultrasound, and light-based devices directed at treating skin laxity. All of these devices target and heat the dermis to induce collagen contraction. Heating of the dermis causes collagen denaturation and immediate collagen contraction in addition to long-term collagen remodeling. Via RF, light, or ultrasound, these skin tightening devices deliver heat to the dermis to create new collagen and induce skin tightening. This chapter will provide an overview of the various skin tightening devices. Copyright © 2011 S. Karger AG, Basel.

  11. The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

    Science.gov (United States)

    Nevalainen, T J; Gavin, J B; Seelye, R N; Whitehouse, S; Donnell, M

    1978-07-01

    The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

  12. Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes.

    Science.gov (United States)

    Sawant, Abhishek C; Bhardwaj, Aishwarya; Banerjee, Kinjal; Jobanputra, Yash; Kumar, Arnav; Parikh, Parth; Kandregula, Krishna C; Poddar, Kanhaiya; Ellis, Stephen G; Nair, Ravi; Corbelli, John; Kapadia, Samir

    2018-02-06

    To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI. Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI. We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected. Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34-0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications. © 2018 Wiley Periodicals, Inc.

  13. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    Science.gov (United States)

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  14. Immunohistochemical evidence for expression of fast-twitch type sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) in German shepherd dogs with dilated cardiomyopathy myocardium.

    Science.gov (United States)

    Summerfield, Nuala; Peters, Mary E; Hercock, Carol A; Mobasheri, Ali; Young, Iain S

    2010-04-01

    Dilated cardiomyopathy (DCM) is one of the most common acquired canine heart diseases. It is particularly common in large and giant breed dogs. Although a great deal is known about the clinical progression and manifestations of the disease, the underlying cellular and molecular mechanisms remain poorly understood. One widely held belief is that calcium-handling abnormalities are critically involved in the disease process. This study investigates the changes in expression of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) isoforms in DCM myocardium from German shepherd dogs. Affected tissue samples were obtained from German shepherd dogs with DCM, euthanized for intractable congestive heart failure while normal myocardial tissue samples were obtained from German shepherd dogs, euthanized for non-cardiovascular reasons. Tissue microarrays containing normal and DCM myocardium samples were prepared, immunostained with SERCA1 and SERCA2 antibodies and analyzed. We were able to demonstrate, for the first time, that while there is little change in the expression of the cardiac isoform (SERCA2), there is clear expression of the fast-twitch skeletal muscle isoform SERCA1 in the myocardium of dogs diagnosed with DCM. We propose that SERCA1 expression is evidence of a natural adaptive response to the impaired Ca2+ handling thought to occur in German shepherd dogs with DCM and heart failure. Copyright 2010 Elsevier B.V. All rights reserved.

  15. Peculiarities of cardiac hemodynamics and functional state of left ventricular myocardium in teenagers with connective heart tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Makhmudova F.M.

    2011-03-01

    Full Text Available The aim of investigation is to study heart hemodynamics in teenagers with connective tissue dysplasia of heart (CTDH. 35 patients ages 12 to 15 years with CTDH have been observed: Group I (n=14 are the patients with mitral valve prolapse (MVP without mitral regurgitation (MR and myxomatous degeneration(MD or isolated minor heart abnormalities (MHA, Group II (n=11are patients with MVP and MR in combination with 1 or2 MHA, and Group III (n=10 are patients with MVP and mixoid degeneration (MD in combination with 2 or more MHA. The control group consisted of 15 patients of the same age without MHA. All the children passed Doppler and echocardiography. According to the results significant changes of cardiohemodynamic indices in patients of Group I were not observed. The changes of size and volume indices of the left ventricle (LV, increase in wall thickness and diastolic dysfunction of the LV were observed in Group II. The significant changes of systolic function of left ventricular myocardium were observed in Group III. The study comes to the conclusion that teenagers with CTDH have definite changes of heart hemodynamics and functional state of left ventricular myocardium. These changes depend on mitral regurgitation, myxomatous degeneration and MHA combination

  16. Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney.

    Directory of Open Access Journals (Sweden)

    Anja Lüttich

    Full Text Available The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.

  17. Increased cross-bridge recruitment contributes to transient increase in force generation beyond maximal capacity in human myocardium.

    Science.gov (United States)

    Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2018-01-01

    Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    Science.gov (United States)

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. {sup 99m}Tc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

    Energy Technology Data Exchange (ETDEWEB)

    Okada, David R. [University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Liu, Zhonglin [University of Arizona School of Medicine, Tucson, AZ (United States); Johnson, Gerald; Okada, Robert D. [University of Oklahoma Health Sciences Center, Oklahoma, OK (United States); University of Tulsa, Tulsa, OK (United States); Beju, Delia [Oklahoma State University School of Medicine, Tulsa, OK (United States); Khaw, Ban An [Northeastern University, Boston, MA (United States)

    2010-10-15

    {sup 99m}Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine {sup 99m}Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). {sup 99m}Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. {sup 99m}Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 {+-} 0.09) (cpm, SEM) than in control (1.74 {+-} 0.07), stunned (1.68 {+-} 0.11), and hibernating (1.59 {+-} 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. {sup 99m}Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 {+-} 0.63) than in control (1.98 {+-} 0.15), stunned (1.79 {+-} 0.08), and hibernating (2.33 {+-} 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase). {sup 99m}Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. {sup 99m}Tc-glucarate uptake was strongly correlated with myocardial necrosis as

  20. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2018-03-01

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p remote zone alterations by quantitative noncontrast T1 mapping provided independent and incremental prognostic information in addition to clinical risk factors and traditional CMR outcome markers. Remote zone alterations may thus represent a novel therapeutic target and a

  1. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology.

    Science.gov (United States)

    Grassberger, M; Baumruker, T; Enz, A; Hiestand, P; Hultsch, T; Kalthoff, F; Schuler, W; Schulz, M; Werner, F J; Winiski, A; Wolff, B; Zenke, G

    1999-08-01

    SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti-inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen-specific or non-specific stimulation. It downregulates the production of Th1 [interleukin (IL)-2, interferon-gamma] and Th2 (IL-4, IL-10) type cytokines after antigen-specific stimulation of a human T-helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin-stimulated transcription of a reporter gene coupled to the human IL-2 promoter in the human T-cell line Jurkat and the IgE/antigen-mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)-alpha promoter in the murine mast-cell line CPII. It does not, however, affect the human TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcgammaRIII receptor. SDZ ASM 981 also prevents the release of preformed pro-inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro.

  2. Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

    International Nuclear Information System (INIS)

    Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

    1990-01-01

    The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

  3. Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

    International Nuclear Information System (INIS)

    Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M.

    1996-01-01

    Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia + EC and was tumour specific. Thus Ia + epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

  4. [The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

    Science.gov (United States)

    Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

    1975-01-01

    The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

  5. Membrane-bound and cytosolic forms of heterotrimeric G proteins in young and adult rat myocardium: influence of neonatal hypo- and hyperthyroidism

    Czech Academy of Sciences Publication Activity Database

    Novotný, Jiří; Bouřová, Lenka; Kolář, František; Svoboda, Petr

    2001-01-01

    Roč. 82, č. 2 (2001), s. 215-224 ISSN 0730-2312 R&D Projects: GA ČR GA305/00/1660; GA MŠk VS97099 Institutional research plan: CEZ:AV0Z5011922 Keywords : development * G proteins * young and adult rat myocardium Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.536, year: 2001

  6. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor

    International Nuclear Information System (INIS)

    Gough, N.M.; Gearing, D.P.; King, J.A.; Willson, T.A.; Hilton, D.J.; Nicola, N.A.; Metcalf, D.

    1988-01-01

    A human homologue of the recently cloned murine leukemia-inhibitory factor (LIF) gene was isolated from a genomic library by using the marine cDNA as a hybridization probe. The nucleotide sequence of the human gene indicated that human LIF has 78% amino acid sequence identity with murine LIF, with no insertions or deletions, and that the region of the human gene encoding the mature protein has one intervening sequence. After oligonucleotide-mediated mutagenesis, the mature protein-coding region of the LIF gene was introduced into the yeast expression vector YEpsec1. Yeast cells transformed with the resulting recombinant could be induced with galactose to produce high levels of a factor that induced the differentiation of murine M1 leukemic cells in a manner analogous to murine LIF. This factor competed with 125 I-labeled native murine LIF for binding to specific cellular receptors on murine cells, compatible with a high degree of structural similarity between the murine and human factors

  7. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    Science.gov (United States)

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-05-15

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

  8. Influence of a transfusion of donor leukocytes treated with 8-methoxypsoralen and long-wave ultraviolet light (PUVA) on skin allograft survival in mice

    International Nuclear Information System (INIS)

    Gruner, S.; Noack, F.; Meffert, H.

    1989-01-01

    The influence of pretransplant donor spleen cell infusions on murine skin graft survival was studied. In dependence on the time interval between transplantation and transfusion an accelerated or delayed rejection of the grafts was observed. If the donor spleen cells were treated with the photosensitizer 8-methoxypsoralen and UVA light (PUVA) a graft prolongation was achieved at all time intervals. Furthermore, the survival of antigenically unrelated grafts was also prolonged. An additional immunosuppressive treatment of the recipients with antilymphocyte serum, but not cyclophosphamide, led to a further prolongation of graft survival. The survival of PUVA treated skin grafts was not longer in recipients preinfused with PUVA treated donor cells compared with untreated hosts. The results presented in this work may have implications in clinical organ transplantation to prevent sensitizing reactions by sparing protective mechanisms for the graft. (author)

  9. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-01-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury

  10. Constitutive activation of Nrf2 induces a stable reductive state in the mouse myocardium

    Directory of Open Access Journals (Sweden)

    Gobinath Shanmugam

    2017-08-01

    Full Text Available Redox homeostasis regulates key cellular signaling pathways in both physiology and pathology. The cell's antioxidant response provides a defense against oxidative stress and establishes a redox tone permissive for cell signaling. The molecular regulation of the well-known Keap1/Nrf2 system acts as sensor responding to changes in redox homeostasis and is poorly studied in the heart. Importantly, it is not yet known whether Nrf2 alone can serve as a master regulator of cellular redox homeostasis without compensation of the transcriptional regulation of antioxidant response element (ARE genes through alternate mechanisms. Here, we addressed this question using cardiac-specific transgenic expression at two different levels of constitutively active nuclear erythroid related factor 2 (caNrf2 functioning independently of Keap1. The caNrf2 mice showed augmentation of glutathione (GSH, the key regulator of the cellular thiol redox state. The Trans-AM assay for Nrf2-binding to the antioxidant response element (ARE showed a dose-dependent increase associated with upregulation of several major antioxidant genes and proteins. This was accompanied by a significant decrease in dihydroethidium staining and malondialdehyde (MDA in the caNrf2-TG mice myocardium. Interestingly, caNrf2 gene-dosage dependent redox changes were noted resulting in generation of a multi-stage model of pro-reductive and reductive conditions in the myocardium of TG-low and TG-high mice, respectively. These data clearly show that Nrf2 levels alone are capable of serving as the master regulator of the ARE. These models provide an important platform to investigate the impact of the Nrf2 system independent of the need to regulate the activity of Keap1 and the consequent exposure to pro-oxidants or electrophiles, which have numerous off-target effects.

  11. Miocárdio hibernante: uma realidade clínica Hibernant myocardium: a clinical reality

    Directory of Open Access Journals (Sweden)

    J.A. Marin-Neto

    1997-12-01

    Full Text Available O conceito da hibernação miocárdica implica a ocorrência de disfunção ventricular crônica, potencialmente reversível, causada por dissinergia regional, dependente de isquemia prolongada. Não tem fisiopatologia elucidada, em parte porque não existem modelos experimentais satisfatórios para seu estudo. Diversos métodos são capazes de demonstrar viabilidade miocárdica nas regiões que não exibem capacidade contrátil basal. O desmascaramento da hibernação nesses territórios pode ser feito mediante demonstração de reserva contrátil, de funcionamento normal da membrana celular, ou de metabolismo preservado. A correta identificação de miocárdio hibernante reveste-se de especial significado clínico, por suas implicações prognósticas quanto a intervenções de revascularização miocárdica, destinadas a reabilitar a função ventricular em muitos pacientes coronariopatas crônicos.Myocardial hibernation is believed to occur in ventricular dyssynergic regions chronically deprived of coronary flow enough to warrant the preservation of contractile function. Pathophysiology of this condition remains largely unclear, mainly because good experimental models for its study are still lacking. Various methods can be clinically employed to detect hibernation in patients with chronic ventricular dysfunction. These methods use the principle of unmasking contractile reserve, or are based on the demonstration of preserved membrane function or myocardium metabolism in the dyssynergic regions. The correct identification of viable hibernating myocardium is crucial in the process of deciding which coronary disease patients would potentially benefit from revascularization procedures.

  12. Proposed derivation of skin contamination and skin decontamination limits

    International Nuclear Information System (INIS)

    Schieferdecker, H.; Koelzer, W.; Henrichs, K.

    1986-01-01

    From the primary dose limits for the skin, secondary dose limits were derived for skin contamination which can be used in practical radiation protection work. Analogous to the secondary dose limit for the maximum permissible body burden in the case of incorporation, dose limits for the 'maximum permissible skin burden' were calculated, with the help of dose factors, for application in the case of skin contamination. They can be derived from the skin dose limit values. For conditions in which the skin is exposed to temporary contamination, a limit of skin contamination was derived for immediately removable contamination and for one day of exposure. For non-removable contamination a dose limit of annual skin contamination was defined, taking into account the renewal of the skin. An investigation level for skin contamination was assumed, as a threshold, above which certain measures must be taken; these to include appropriate washing not more than three times, with the subsequent procedure determined by the level of residual contamination. The dose limits are indicated for selected radionuclides. (author)

  13. Your Skin

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Skin KidsHealth / For Kids / Your Skin What's in this ... body) are really dead skin cells. Bye-Bye Skin Cells These old cells are tough and strong, ...

  14. Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT).

    Science.gov (United States)

    Kreiling, R; Hollnagel, H M; Hareng, L; Eigler, D; Lee, M S; Griem, P; Dreessen, B; Kleber, M; Albrecht, A; Garcia, C; Wendel, A

    2008-06-01

    The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)> or = 3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.

  15. The murine Cd48 gene: allelic polymorphism in the IgV-like region.

    Science.gov (United States)

    Cabrero, J G; Freeman, G J; Reiser, H

    1998-12-01

    The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48.

  16. Dry Skin Relief

    Science.gov (United States)

    ... on a budget Skin care products Skin care secrets Skin lighteners Skin of color Summer skin problems ... condition, such as eczema. Additional related information Dermatologists' top tips for relieving dry skin FIND A DERMATOLOGIST ...

  17. Analysis of the capacity to produce IL-3 in murine AIDS

    DEFF Research Database (Denmark)

    Neuenschwander, A U; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Adult C57BL/6 mice infected with LP-BM5 murine leukaemia virus represent a model of murine AIDS (MAIDS). In this study we have analysed the capacity of CD4+ T cells from infected mice to produce IL-3 following stimulation with ConA for 24-72 h. In contrast to the position with IL-2, the production...

  18. Skin mites in mice (Mus musculus): high prevalence of Myobia sp. (Acari, Arachnida) in Robertsonian mice.

    Science.gov (United States)

    Sastre, Natalia; Calvete, Oriol; Martínez-Vargas, Jessica; Medarde, Nuria; Casellas, Joaquim; Altet, Laura; Sánchez, Armand; Francino, Olga; Ventura, Jacint

    2018-05-04

    Myobia sp. and Demodex sp. are two skin mites that infest mice, particularly immunodeficient or transgenic lab mice. In the present study, wild house mice from five localities from the Barcelona Roberstonian system were analysed in order to detect skin mites and compare their prevalence between standard (2n = 40) and Robertsonian mice (2n > 40). We found and identified skin mites through real-time qPCR by comparing sequences from the mitochondrial 16S rRNA and the nuclear 18S rRNA genes since no sequences are available so far using the mitochondrial gene. Fourteen positive samples were identified as Myobia musculi except for a deletion of 296 bp out to 465 bp sequenced, and one sample was identified as Demodex canis. Sampling one body site, the mite prevalence in standard and Robertsonian mice was 0 and 26%, respectively. The malfunction of the immune system elicits an overgrowth of skin mites and consequently leads to diseases such as canine demodicosis in dogs or rosacea in humans. In immunosuppressed mice, the probability of developing demodicosis is higher than in healthy mice. Since six murine toll-like receptors (TLRs) are located in four chromosomes affected by Robertsonian fusions, we cannot dismiss that differences in mite prevalence could be the consequence of the interruption of TLR function. Although ecological and/or morphological factors cannot be disregarded to explain differences in mite prevalence, the detection of translocation breakpoints in TLR genes or the analysis of TLR gene expression are needed to elucidate how Robertsonian fusions affect the immune system in mice.

  19. Characterization of oily mature skin by biophysical and skin imaging techniques.

    Science.gov (United States)

    de Melo, M O; Maia Campos, P M B G

    2018-02-13

    The skin is a complex biological system and may suffer change according to the environmental factors, as higher temperatures can increase sebum excretion, presenting oiliness and acne. These alterations can persist during the aging and provoke more changes in aged skin. In this study we evaluated the mature oily skin characteristics using biophysical and skin imaging techniques. Sixty healthy female subjects, aged between 39 and 55 years old were recruited and separated into 2 groups according to their skin type: normal/dry and oily skin. The skin was evaluated in terms of stratum corneum water content, transepidermal water loss (TEWL) sebum content, dermis thickness and echogenicity, skin microrelief, and pores content. The mature oily skin presented no significant differences when compared to the normal/dry skin on the stratum corneum water content and TEWL parameters. The sebum content was significantly higher on the oily skin group. The microrelief analysis showed an increase of skin roughness values in the oily skin and increase of scaliness in the normal/dry skin. The oily skin showed lower dermis echogenicity mainly in the frontal region and higher dermis thickness when compared to normal/dry skin. The mature oily skin showed different characteristics from normal/dry skin in terms of sebum content, microrelief parameters, and dermis thickness. This way, the characterization of mature oily skin in an objective way is very important to development of dermocosmetic products for more effective treatments focused specially on this type of skin. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Cure of skin cancer. Surgical cure of skin cancer

    International Nuclear Information System (INIS)

    Zikiryakhodjaev, D.Z.; Sanginov, D.R.

    2001-01-01

    In this chapter authors studied the cure of skin cancer in particular the surgical cure of skin cancer. They noted that surgical cure of skin cancer is remain one of the primary and most important methods in treatment of skin cancer

  1. Quantitative shear wave imaging optical coherence tomography for noncontact mechanical characterization of myocardium

    Science.gov (United States)

    Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

    2015-03-01

    Optical coherence elastography (OCE) is an emerging low-coherence imaging technique that provides noninvasive assessment of tissue biomechanics with high spatial resolution. Among various OCE methods, the capability of quantitative measurement of tissue elasticity is of great importance for tissue characterization and pathology detection across different samples. Here we report a quantitative OCE technique, termed quantitative shear wave imaging optical coherence tomography (Q-SWI-OCT), which enables noncontact measurement of tissue Young's modulus based on the ultra-fast imaging of the shear wave propagation inside the sample. A focused air-puff device is used to interrogate the tissue with a low-pressure short-duration air stream that stimulates a localized displacement with the scale at micron level. The propagation of this tissue deformation in the form of shear wave is captured by a phase-sensitive OCT system running with the scan of the M-mode imaging over the path of the wave propagation. The temporal characteristics of the shear wave is quantified based on the cross-correlation of the tissue deformation profiles at all the measurement locations, and linear regression is utilized to fit the data plotted in the domain of time delay versus wave propagation distance. The wave group velocity is thus calculated, which results in the quantitative measurement of the Young's modulus. As the feasibility demonstration, experiments are performed on tissuemimicking phantoms with different agar concentrations and the quantified elasticity values with Q-SWI-OCT agree well with the uniaxial compression tests. For functional characterization of myocardium with this OCE technique, we perform our pilot experiments on ex vivo mouse cardiac muscle tissues with two studies, including 1) elasticity difference of cardiac muscle under relaxation and contract conditions and 2) mechanical heterogeneity of the heart introduced by the muscle fiber orientation. Our results suggest the

  2. Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

    DEFF Research Database (Denmark)

    Ewald, David A.; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT......-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false...... discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL...

  3. Effects of Using Tricaine Methanesulfonate and Metomidate before Euthanasia on the Contractile Properties of Rainbow Trout (Oncorhynchus mykiss) Myocardium.

    Science.gov (United States)

    Roberts, Jordan C; Syme, Douglas A

    2016-01-01

    Because many anesthetics work through depressing cell excitability, unanesthetized euthanasia has become common for research involving excitable tissues (for example muscle and nerve) to avoid these depressive effects. However, anesthetic use during euthanasia may be indicated for studies involving isolated tissues if the potential depressive effects of brief anesthetic exposure dissipate after subsequent tissue isolation, washout, and saline perfusion. We explore this here by measuring whether, when applied prior to euthanasia, standard immersion doses of 2 fish anesthetics, tricaine methanesulfonate (TMS; 100 mg/L, n = 6) and methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (metomidate, 10 mg/L, n = 6), have residual effects on the contractile properties (force and work output) of isolated and saline-perfused ventricular compact myocardium from rainbow trout (Oncorhynchus mykiss). Results suggest that direct exposure of muscle to immersion doses of TMS-but not metomidate-impairs muscle contractile performance. However, brief exposure (2 to 3 min) to either anesthetic during euthanasia only-providing that the agent is washed out prior to tissue experimentation-does not have an effect on the contractile properties of the myocardium. Therefore, the use of TMS, metomidate, and perhaps other anesthetics that depress cell excitability during euthanasia may be indicated when conducting research on isolated and rinsed tissues.

  4. Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

    Science.gov (United States)

    Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

    2011-10-15

    Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. Detection of homing-in of stem cells labeled with technetium-99m hexamethylpropyleneamine oxime in infarcted myocardium after intracoronary injection

    International Nuclear Information System (INIS)

    Patel, Chetan D; Agarwal, Snehlata; Seth, Sandeep; Mohanty, Sujata; Aggarwal, Himesh; Gupta, Namit

    2014-01-01

    Bone marrow stem cells having myogenic potential are promising candidates for various cell-based therapies for myocardial disease. We present here images showing homing of technetium-99m (Tc-99m) hexamethylpropyleneamine oxime (HMPAO) labeled stem cells in the infarcted myocardium from a pilot study conducted to radio-label part of the stem cells in patients enrolled in a stem cell clinical trial for recent myocardial infarction

  6. Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium.

    Science.gov (United States)

    Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

    2016-05-01

    Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

  7. Skin dosimetry - radiological protection aspects of skin dosimetry

    International Nuclear Information System (INIS)

    Dennis, J.A.

    1991-01-01

    Following a Workshop in Skin Dosimetry, a summary of the radiological protection aspects is given. Aspects discussed include routine skin monitoring and dose limits, the need for careful skin dosimetry in high accidental exposures, techniques for assessing skin dose at all relevant depths and the specification of dose quantities to be measured by personal dosemeters and the appropriate methods to be used in their calibration. (UK)

  8. A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

    Energy Technology Data Exchange (ETDEWEB)

    Akram, Muhammad [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of); Shin, Iljin [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Kim, Kyeong-A; Noh, Dabi [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of); Baek, Seung-Hoon; Chang, Sun-Young [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Kim, Hyoungsu, E-mail: hkimajou@ajou.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon (Korea, Republic of); Bae, Ok-Nam, E-mail: onbae@hanyang.ac.kr [College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan (Korea, Republic of)

    2016-09-15

    Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPD 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.

  9. Cutaneous skin tag

    Science.gov (United States)

    Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

  10. Effect of amiodarone on the conversion of thyroxine to triiodotironine in rat myocardium in vivo and in vitro

    International Nuclear Information System (INIS)

    Ceppi, J.A.; Gonzalez, M.R.; Zaninovich, A.A.

    1988-01-01

    It was studied the effect of the antiarrhythmic drug amiodarone, on the conversion of T 4 to T 3 by rat myocardium and liver. Wistar rats were injected with amiodarone (AM) or iopanoic acid (IOP), afterwards the liver and the heart were homogenized in krebs-ringer phosphate. Aliquots of 400μl of the homogenized were separated and DTT 8mM and 10 -2 μCi 125 I-T 4 or 125 I-T 3 were added (either the conversion of T 4 to T 3 or degradation of T 3 are measured). In vitro: were added AM 0,1 mM or IOP 10mM. Incubation proceeded for 2 hours at 37 deg C and aliquots were chromatographied. The conversion of T 4 to T 3 in the myocardium and liver in vivo decreased, but in vitro did not have any deiodination of T 4 and the IOP reduced the production of T 3 by heart. Neither drug altered the deiodination of T 3 by heart or liver homogenates. Serum TSH and T 3 were decreased by AM and serum T 4 increased. IOP caused similar variations in T 4 and T 3 , but serum TSH was increased. It is concluded that blocking the T 3 miocardial production by AM may not be the cause of the antiarrhythmic effect of the drug. (M.E.L.) [es

  11. Artificial skin and patient simulator comprising the artificial skin

    NARCIS (Netherlands)

    2011-01-01

    The invention relates to an artificial skin (10, 12, 14), and relates to a patient simulator (100) comprising the artificial skin. The artificial skin is a layered structure comprising a translucent cover layer (20) configured for imitating human or animal skin, and comprising a light emitting layer

  12. 19 CFR 12.63 - Seal-skin or sea-otter-skin waste.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Seal-skin or sea-otter-skin waste. 12.63 Section... OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Fur-Seal Or Sea-Otter Skins § 12.63 Seal-skin or sea-otter-skin waste. Seal-skin or sea-otter-skin waste composed of small pieces not large enough to be...

  13. Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

    Science.gov (United States)

    Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

    2018-05-09

    Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

  14. T1 mapping of the myocardium: Intra-individual assessment of the effect of field strength, cardiac cycle and variation by myocardial region

    Directory of Open Access Journals (Sweden)

    Kawel Nadine

    2012-05-01

    Full Text Available Abstract Background Myocardial T1 relaxation time (T1 time and extracellular volume fraction (ECV are altered in the presence of myocardial fibrosis. The purpose of this study was to evaluate acquisition factors that may result in variation of measured T1 time and ECV including magnetic field strength, cardiac phase and myocardial region. Methods 31 study subjects were enrolled and underwent one cardiovascular MR exam at 1.5 T and two exams at 3 T, each on separate days. A Modified Look-Locker Inversion Recovery (MOLLI sequence was acquired before and 5, 10, 12, 20, 25 and 30 min after administration of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist at 1.5 T (exam 1. For exam 2, MOLLI sequences were acquired at 3 T both during diastole and systole, before and after administration of Gd-DTPA (0.15 mmol/kg Magnevist.Exam 3 was identical to exam 2 except gadobenate dimeglumine was administered (Gd-BOPTA; 0.1 mmol/kg Multihance. T1 times were measured in myocardium and blood. ECV was calculated by (ΔR1myocardium/ΔR1blood*(1-hematocrit. Results Before gadolinium, T1 times of myocardium and blood were significantly greater at 3 T versus 1.5 T (28% and 31% greater, respectively, p  Conclusion ECV is similar at field strengths of 1.5 T and 3 T. Due to minor variations in T1 time and ECV during the cardiac cycle and in different myocardial regions, T1 measurements should be obtained at the same cardiac phase and myocardial region in order to obtain consistent results.

  15. Acute Febrile Illness and Complications Due to Murine Typhus, Texas, USA1,2.

    Science.gov (United States)

    Afzal, Zeeshan; Kallumadanda, Sunand; Wang, Feng; Hemmige, Vagish; Musher, Daniel

    2017-08-01

    Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states.

  16. Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model.

    Science.gov (United States)

    Mohammad, Haroon; Cushman, Mark; Seleem, Mohamed N

    2015-01-01

    The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections.

  17. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  18. Matching the skin barrier to the skin type.

    Science.gov (United States)

    Thompson, Hyacinth; North, Jacqui; Davenport, Rebecca; Williams, Julia

    Peristomal skin problems are thought to be common (Herlufsson et al, 2006; Williams et al, 2010), and can interfere with the security of stoma products. Stoma patients are reliant on the integrity of their peristomal skin to maintain a normal lifestyle. Bekkers et al (1996) highlighted that, if the peristomal skin becomes damaged, it not only affects the person physically, but also psychologically, ultimately prolonging rehabilitation and adaptation to the stoma. Therefore, it can be concluded that maintaining skin integrity is a basic and essential skill in ensuring good stoma management. This article explores the assessment of four stoma patients, highlighting the importance of matching their skin type with their skin barrier for optimum skin protection. The patients have kindly agreed for their case studies to be published as a means of informing others. All names have been changed in line with Nursing and Midwifery Council (2010) guidelines to maintain patient confidentiality. This article was originally presented at the World Council of Enterostomal Therapists' (WCET) annual conference in 2010, receiving first prize at poster presentations.

  19. Reemergence of Murine Typhus in the US

    Centers for Disease Control (CDC) Podcasts

    2015-04-21

    Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

  20. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  1. Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

    Directory of Open Access Journals (Sweden)

    Teresa Fiebig

    Full Text Available Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

  2. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    OpenAIRE

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

  3. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

    Directory of Open Access Journals (Sweden)

    Ching Wen Tseng

    Full Text Available Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA, exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD/severe combined immune deficiency (SCID/IL2rγnull (NSG mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

  4. Age-associated decrease in GDNF and its cognate receptor GFRα-1 protein expression in human skin.

    Science.gov (United States)

    Adly, Mohamed A; Assaf, Hanan A; Hussein, Mahmoud Rezk Abdelwahed

    2016-06-01

    Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations. © 2016 The Authors. International Journal of Experimental Pathology © 2016

  5. Skin Cancer.

    Science.gov (United States)

    Linares, Miguel A; Zakaria, Alan; Nizran, Parminder

    2015-12-01

    Skin cancer accounts for most malignancies across the globe. They are primarily divided into melanoma and nonmelanoma skin malignancies. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Fair skin and chronic ultraviolet B exposure are the most important risk factors. Primary prevention is achieved by avoiding sun exposure and tanning beds. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Moist skin care can diminish acute radiation-induced skin toxicity

    International Nuclear Information System (INIS)

    Momm, F.; Weissenberger, C.; Bertelt, S.; Henke, M.

    2003-01-01

    Background: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. Patients and Methods: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. Results: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). Conclusion: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors. (orig.)

  7. Skin cancer

    International Nuclear Information System (INIS)

    Yamada, Michiko

    1992-01-01

    This chapter reviews the development of skin cancer associated with radiation, focusing on the knowledge of A-bomb radiation-induced skin cancer. Since the discovery of X radiation in 1895, acute and chronic radiation dermatitis has been the first matter of concern. Then, in 1902, skin cancer found among radiological personnel has posed a social problem. In earlier study determining the relationship between skin cancer and A-bomb radiation, there is no increase in the incidence of either skin cancer or precancerous condition during the first 20 years after A-bombing. More recent studies have showed that there is a significant correlation between the incidence of skin cancer and distance from the hypocenter; and the incidence of skin cancer is found to be remarkably increased since 1975 in the group exposed at ≤2,000 m. Excess relative risk is 2.2 at one Gy dose. The incidence of skin cancer is also found to be extremely increased with aging. Relative risk is high in younger A-bomb survivors at the time of exposure. Histologically, basal cell carcinoma is more senstitive to ionizing radiation than squamous cell carcinoma. (N.K.)

  8. Skin temperature during sunbathing--relevance for skin cancer

    DEFF Research Database (Denmark)

    Petersen, Bibi; Philipsen, Peter Alshede; Wulf, Hans Christian

    2014-01-01

    It has been found that exposure to heat and infrared radiation (IR) can be carcinogenic, and that a combination of ultraviolet radiation (UVR) and IR possibly amplifies carcinogenesis. To investigate how the skin temperature is affected by sunbathing, we measured the skin temperature on 20 healthy...... volunteers over 6 days' sun holiday in Egypt. Temperatures were measured with an infrared thermometer gun at 8 skin sites on the volunteers while they were indoors in the morning and when sunbathing during the day. Skin temperatures were higher during sunbathing (33.5 °C ± 2.1 °C) (mean ± SD) than when...... indoors in the morning (32.6 °C ± 1.4 °C) (mean ± SD) (P skin temperature for men was higher than for women by 0.40 °C in the morning (P = 0.02) and by 0.44 °C during sunbathing (P skin temperature, which possibly...

  9. Image analysis of skin color heterogeneity focusing on skin chromophores and the age-related changes in facial skin.

    Science.gov (United States)

    Kikuchi, Kumiko; Masuda, Yuji; Yamashita, Toyonobu; Kawai, Eriko; Hirao, Tetsuji

    2015-05-01

    Heterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age-related changes. A facial imaging system equipped with an illumination unit and a high-resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment-specific image-processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized. The proposed pigment-specific image-processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age-related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin. We have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Selective Retrograde Venous Revascularization of the Myocardium when PCI or CABG Is Impossible: Investigation in a Porcine Model

    DEFF Research Database (Denmark)

    Møller, Christian H; Nørgaard, Martin A; Gøtze, Jens P

    2008-01-01

    We investigated the possibility of nourishing the myocardium through selective retrograde coronary venous bypass grafting (CVBG) with an off-pump technique and evaluated various methods of monitoring the physiological effects of this procedure. In a porcine model, the left internal mammary artery...... tension decreased, but with time some recovery was seen. Cardiac troponin T was elevated. Histological analysis showed ischemic changes. In control pigs, microdialysis was performed for 1.5 hours up to LAD artery ligation, after which all pigs died in ventricular fibrillation arrest. No increase...

  11. Skin autofluorescence reflects individual seasonal UV exposure, skin photodamage and skin cancer development in organ transplant recipients.

    Science.gov (United States)

    Togsverd-Bo, Katrine; Philipsen, Peter Alshede; Hædersdal, Merete; Wulf, Hans Christian Olsen

    2018-01-01

    Ultraviolet radiation (UVR)-induced skin cancers varies among organ transplant recipients (OTRs). To improve individual risk assessment of skin cancer, objectively quantified skin photodamage is needed. We measured personal UVR-exposure dose in OTRs and assessed the relation between individual UVR exposure, skin cancer and objectively measured photodamage in terms of skin autofluorescence, pigmentation, and black light-evaluated solar lentigines. Danish OTRs with (n=15) and without a history of skin cancer (n=15) kept sun diaries from May to September and wore personal dosimeters recording time-stamped UVR doses in standard erythema doses (SED). Photodamage was quantified as skin autofluorescence with excitation at 370nm (F370) and 430nm (F430), skin pigmentation (pigment protection factor, PPF), and black light-evaluated solar lentigines. OTRs with skin cancer received a higher UVR dose than OTRs without skin cancer (median 116 SED vs. 67 SED, p=0.07) and UVR exposure doses were correlated with increased PPF (p=0.052) and F370 on the shoulder (F370 shoulder ) (p=0.04). We found that skin cancer was associated with F370 shoulder (OR 10.53, CI 3.3-31,938; p=0.018) and time since transplantation (OR 1.34, CI 0.95-1.91, p=0.097). A cut-off at 7.2 arbitrary units, 89% of OTRs with skin cancer had F370 shoulder values above 7.2 arbitrary units and F370 shoulder was additionally related to patient age (p=0.09) and black light-evaluated solar lentigines (p=0.04). F370 autofluorescence indicates objectively measured photodamage and may be used for individual risk assessment of skin cancer development in OTRs. Copyright © 2017. Published by Elsevier B.V.

  12. Expression of biologically active murine interleukin-18 in Lactococcus lactis.

    Science.gov (United States)

    Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

    2016-11-01

    The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL -1 and 0.6-0.7 ng mL -1 , respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Murine typhus in two travelers returning from Bali, Indonesia: an underdiagnosed disease.

    Science.gov (United States)

    Takeshita, Nozomi; Imoto, Kazuya; Ando, Shuji; Yanagisawa, Kunio; Ohji, Goh; Kato, Yasuyuki; Sakata, Akiko; Hosokawa, Naoto; Kishimoto, Toshio

    2010-01-01

    Two Japanese travelers from Bali were diagnosed with murine typhus in Japan during the same period. Although one had only mild illness, the other experienced liver and kidney dysfunction. Murine typhus may be missed not only in endemic areas around the world, but also in travelers, especially those returning from marine resorts in these areas. © 2010 International Society of Travel Medicine.

  14. Is skin penetration a determining factor in skin sensitization ...

    Science.gov (United States)

    Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow self-evident truth borne out from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

  15. Epidemiology of "fragile skin": results from a survey of different skin types

    Directory of Open Access Journals (Sweden)

    Haftek M

    2013-12-01

    Full Text Available Marek Haftek,1 Christine Coutanceau,2 Charles Taïeb3 1Université Lyon 1, Laboratoire de Recherche Dermatologique, Faculté de Médecine et de Pharmacie, Lyon, 2Département Médical, Laboratoires Dermatologiques A-Derma, Lavaur, 3Public Health, Pierre Fabre SA, Paris, France Background: Epidemiologic information regarding the prevalence of "fragile skin" in different adult populations is currently limited. The objective of the current survey was to assess the occurrence of perceived "fragile skin" across different skin types in the general adult population. Methods: Individuals aged 15–65 years from five representative geographic regions (France, Spain, Sweden, Japan, and the US were interviewed and grouped into the following skin types: Caucasian North skin (n=1,218, Caucasian South skin (n=1,695, Asian skin (n=1,500, and Black skin (n=500. The main survey question was "In your opinion, do you have fragile skin?" Concepts relating to the nature and appearance of an individual's skin were also evaluated. Results: A total of 4,913 individuals were interviewed. Subjects in the Caucasian North, Caucasian South, Asian, and Black skin type groups responded positively to the question "In your opinion, do you have fragile skin?" in the following proportions: 24.44%, 29.71%, 52.67%, and 42.20%, respectively. With the exception of individuals in the Black skin group, "fragile skin" was prevalent in significantly more women than men (P<0.0001. Compared with other age categories, the prevalence of "fragile skin" was significantly higher in individuals aged 15–34 years (P<0.0001, regardless of skin type. In general, individuals reporting "fragile skin" were 2–3-fold more likely to respond positively to a series of questions relating to the nature and appearance of their skin. The prevalence of "fragile skin" was also higher in individuals who experienced dermatosis (skin lesions of any type in the previous 12 months. Conclusion: Whilst these

  16. Skin Graft

    OpenAIRE

    Shimizu, Ruka; Kishi, Kazuo

    2012-01-01

    Skin graft is one of the most indispensable techniques in plastic surgery and dermatology. Skin grafts are used in a variety of clinical situations, such as traumatic wounds, defects after oncologic resection, burn reconstruction, scar contracture release, congenital skin deficiencies, hair restoration, vitiligo, and nipple-areola reconstruction. Skin grafts are generally avoided in the management of more complex wounds. Conditions with deep spaces and exposed bones normally require the use o...

  17. 16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

    Science.gov (United States)

    Lee, Byung Chul; Kim, Dong Hyun; Lee, Iljung; Choe, Yearn Seong; Chi, Dae Yoon; Lee, Kyung-Han; Choi, Yong; Kim, Byung-Tae

    2008-06-26

    We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate ( 2) and Na99mTcO 4 in the presence of Cr(CO)6 and CrCl3, followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41%ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that 99mTc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to 99mTc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.

  18. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  19. In vivo effect of the D-(-) isomer or natural form of 3-hydroxybutyrate on initial release of lactate dehydrogenase from the acutely ischaemic myocardium.

    Science.gov (United States)

    Lammerant, J; Huynh-Thu, T; Kolanowski, J

    1986-07-01

    D-(-)-3-hydroxybutyrate, the isomer found in the circulation and in the urine of diabetic patients, generally is believed to be the physiologically important form of 3-hydroxybutyrate [10]. Little is known concerning the effects of an elevated plasma level of the D-(-) isomer of 3-hydroxybutyrate upon the acutely ischaemic heart. Using anaesthetized intact dogs with a balloon catheter inserted into the proximal part of the left anterior descending coronary artery (LAD), we have recently demonstrated that a 1 mM ketonaemia induced with the arginine salt of D-(-)-3-hydroxybutyric acid reduces the uptake of non-esterified fatty acids (NEFA) in the myocardial area distal to the inflated balloon [4]. The question arises as to whether the concomitant increase in ketone uptake in this area could be detrimental to the acutely ischaemic myocardium. Indeed, a previous study on isolated coronary ligated hearts from normal rats has shown that the rate of release of lactate dehydrogenase (LDH) during the first 90 min of ischaemia can be enhanced by replacing glucose (11 mM) in the perfusion fluid with either albumin-bound palmitate (0.9 mM) or sodium DL-3-hydroxybutyrate (10 mM) as the sole energy substrate [11]. This would suggest that the ketone might be as deleterious as its metabolic precursors for membrane integrity in the acutely ischaemic myocardium. In the present report, we examine the effect of arginine D-(-)-3-hydroxybutyrate on LDH release from ischaemic myocardium in our in vivo preparation. The dogs were treated with lidocaine in order to minimize the frequency and, hence, the adverse metabolic effects of ectopic beats.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    Science.gov (United States)

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

  1. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

    Science.gov (United States)

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  2. Thallium 201 scintigraphy of the myocardium. A bibliographical survey for image optimisation

    International Nuclear Information System (INIS)

    Chatelier, Luc.

    1979-01-01

    At the request of a Nuclear Medicine Service we compiled a review of the literature on thallium 201 myocardium scintigraphy in order to define the optimum parameters for image acquisition; included also are the bibliograhical references of studies on the sensitivities, specificities and accuracies of this technique as compared with electrocardiography in the diagnosis and evaluation of ischemic heart diseases. This examination seems to have a part to play at all stages in the evaluation of ischemic heart diseases, whether for the detection (ischemia) emergency handling (thrombosis) or post-surgical checking (permeability of an aorto-coronary transplant) of these diseases, the great frequency and gravity of which have no longer to be proved. This study covers the whole period since thallium scintigraphy began (1970) until June 1978. Thallium seems to have a great future in cardiology and may be even in other fields since its use is quoted (in only a few publications as yet) for brain, kidney and pancreas scintigraphy [fr

  3. Wearable Multi-Channel Microelectrode Membranes for Elucidating Electrophysiological Phenotypes of Injured Myocardium

    Science.gov (United States)

    Cao, Hung; Yu, Fei; Zhao, Yu; Zhang, Xiaoxiao; Tai, Joyce; Lee, Juhyun; Darehzereshki, Ali; Bersohn, Malcolm; Lien, Ching-Ling; Chi, Neil C.; Tai, Yu-Chong; Hsiai, Tzung K.

    2014-01-01

    Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrated the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights in long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. PMID:24945366

  4. Transmural Variation and Anisotropy of Microvascular Flow Conductivity in the Rat Myocardium

    KAUST Repository

    Smith, Amy F.

    2014-05-28

    Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

  5. Preparation of Artificial Skin that Mimics Human Skin Surface and Mechanical Properties.

    Science.gov (United States)

    Shimizu, Rana; Nonomura, Yoshimune

    2018-01-01

    We have developed an artificial skin that mimics the morphological and mechanical properties of human skin. The artificial skin comprises a polyurethane block possessing a microscopically rough surface. We evaluated the tactile sensations when skin-care cream was applied to the artificial skin. Many subjects perceived smooth, moist, and soft feels during the application process. Cluster analysis showed that these characteristic tactile feels are similar to those when skin-care cream is applied to real human skin. Contact angle analysis showed that an oil droplet spread smoothly on the artificial skin surface, which occurred because there were many grooves several hundred micrometers in width on the skin surface. In addition, when the skin-care cream was applied, the change in frictional force during the dynamic friction process increased. These wetting and frictional properties are important factors controlling the similarity of artificial skin to real human skin.

  6. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  7. Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug.

    Science.gov (United States)

    Joseph, Laurie B; Composto, Gabriella M; Perez, Roberto M; Kim, Hong-Duck; Casillas, Robert P; Heindel, Ned D; Young, Sherri C; Lacey, Carl J; Saxena, Jaya; Guillon, Christophe D; Croutch, Claire R; Laskin, Jeffrey D; Heck, Diane E

    2018-09-01

    Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal appendages and at the dermal/epidermal junction. In control mice, 48-61% of mast cells were degranulated. SM exposure (1.4g/m 3 in air for 6min) resulted in increased numbers of degranulated mast cells 1-14days post-exposure. Treatment of mice topically with an indomethacin choline bioisostere containing prodrug linked by an aromatic ester-carbonate that targets cyclooxygenases (COX) enzymes and acetylcholinesterase (1% in an ointment) 1-14days after SM reduced skin inflammation and injury and enhanced tissue repair. This was associated with a decrease in mast cell degranulation from 90% to 49% 1-3days post SM, and from 84% to 44% 7-14days post SM. These data suggest that reduced inflammation and injury in response to the bifunctional indomethacin prodrug may be due, at least in part, to abrogating mast cell degranulation. The use of inhibitors of mast cell degranulation may be an effective strategy for mitigating skin injury induced by SM. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Skin Aging

    Science.gov (United States)

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  9. Skin Conditions

    Science.gov (United States)

    Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

  10. Angiographically demonstrated coronary collaterals predict residual viable myocardium in patients with chronic myocardial infarction. A regional metabolic study

    International Nuclear Information System (INIS)

    Fukai, Masumi; Ii, Masaaki; Nakakoji, Takahiro

    2000-01-01

    Angiographical demonstration of coronary collateral circulation may suggest the presence of residual viable myocardium. The development of coronary collaterals was judged according to Rentrop's classification in 37 patients with old anteroseptal myocardial infarction and 13 control patients with chest pain syndrome. The subjects with myocardial infarction were divided into 2 groups: 17 patients with the main branch of the left coronary artery clearly identified by collateral blood flow from the contralateral coronary artery [Coll (+) group, male/female 10/7, mean age 56.6 years] and 20 patients with obscure coronary trunk [Coll (-) group, male/female 16/4, mean age 54.9 years]. Thallium-201 myocardial scintigraphy and examination of local myocardial metabolism were carried out by measuring the flux of lactic acid under dipyridamole infusion load. Coronary stenosis of 99% or total occlusion was found in only 5 of 20 patients (25%) in the Coll (-) group but in 16 of 17 patients (94%) in the Coll (+) group (p<0.001). Redistribution of myocardial scintigraphy was found in 11 of 15 patients (73%) in the Coll (+) group, but only 3 of 18 patients (17%) in the Coll (-) group (p<0.01). The myocardial lactic acid extraction rate was -13.2±17.0% in the Coll (+) group, but 9.1±13.2% in the Coll (-) group (p<0.001). These results suggest that coronary collateral may contribute to minimizing the infarct area and to prediction of the presence of viable myocardium. (author)

  11. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics Skin Cancer Treatment Glossary Information on medications and procedures ...

  12. The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

    Directory of Open Access Journals (Sweden)

    Marcell Cserhalmi

    2017-09-01

    Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

  13. Skin Diseases: Skin and Sun—Not a good mix

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin and Sun —Not a good mix Past Issues / ... of this page please turn Javascript on. Good skin care begins with sun safety. Whether it is ...

  14. Preclinical pharmacological study of 99mTcN(NOET)2 and comparison with 201Tl in redistribution of ischemia myocardium

    International Nuclear Information System (INIS)

    Wang, J.C.; Zhang, J.B.; Wang, Q.; Mi, H.Z.; Wang, X.B.

    2002-01-01

    Aim: To study the biological properties of the myocardial imaging agent 99m TcN(NOET) 2 and compare with 201 Tl in redistribution of ischemia myocardium. Materials and Methods: To prepared the 99m TcN(NOET) 2 complex, the intermediate [ 99m TcN] 2+ and ligand NOET were synthesized. In the presence of reducer and the doner of N, the [ 99m Tc=N] 2+ could be synthesized at 100, then NOET was added, 99m TcN(NOET) 2 was formed at room temperature. 201 Tl was provided by the Department of Isotope, China Institute of Atomic Energy. Five dogs were from the Fu Wai experimental animal feeding center, two of them were made into ischemia myocardium models by ligating some coronary artery branches were demonstrated by X-ray coronary angiography, the extent of stenosis of those blood vessels was over 90%. Dynamic imaging of rest was performed respectively in three normal dogs after injecting a dose of 555MBq (15mCi) of 99m TcN(NOET) 2 complex up to two hours. The whole body imaging planar and tomography imaging was carried out respectively at fixed time intervals during two hours in order to obtain the time-activity curves of heart, lung and liver, in vivo biodistribution and quality analysis of myocardial images. Moreover, intravenous blood samples were collected at different times to gain the kinetics of blood clearance. Stress and redistribution imaging underwent in two dogs with ischemia myocardium. Dipyridamol was given intravenously at a dose of 0.6mg/Kg in 4 mins. Stress :9 9m TcN(NOET) 2 myocardial SPECT imaging was performed at 30, 70 and 110 min after injection of 99m TcN(NOET) 2 complex, stress 201 Tl myocardial SPECT imaging was carried out 10 min and redistribution imaging 4 hr after injection of 55.5MBq (1.5mCi) 201 Tl chloride. The tests of 99m TcN(NOET) 2 and 201 Tl were performed respectively in the same dog within 10 days, in order to obtain a comparison between two myocardial redistribution imaging. Results: Radiochemical purity of 99m TcN(NOET) 2 was 98.41%

  15. Skin Pigmentation Disorders

    Science.gov (United States)

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  16. [A case of skin autograft for skin ulcers in ichthyosis].

    Science.gov (United States)

    Li, Shiwei; Yang, Xiaodong; Liu, Lijun; Tang, Xueyang

    2017-10-28

    Ichthyosis refers to a group of skin diseases characterized by abnormal keratinization of the epidermis, resulting in dryness, roughness and scale of the skin. A girl with ichthyosis, who presented with skin ulcers and infection of the right dorsal foot, was admitted to our department. An autologous razor-thin skin grafting procedure was performed to repair the skin ulcers after debridement and vacuum sealing drain. After 8 months of follow-up, both the donor and recipient site healed well and there were no newly formed ulcers or infections. Although the skin quality of ichthyosis is poor, the lesion area can still be used as donor or recipient cite.

  17. Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin

    NARCIS (Netherlands)

    Eweje, M.O.

    2016-01-01

    The studies in this thesis describes the barrier defects in Atopic Dermatitis (AD) skin and various techniques to develop AD Human Skin Equivalents (HSEs) which can be used to better understand the role of several factors in the pathogenesis of AD skin. The results described show that Inflammation

  18. cDNA cloning and characterization of mouse DTEF-1 and ETF, members of the TEA/ATTS family of transcription factors.

    Science.gov (United States)

    Yockey, C E; Shimizu, N

    1998-02-01

    Members of the TEA/ATTS family of transcription factors have been found in most representative eukaryotic organisms. In vertebrates, the TEA family contains at least four members, which share overlapping DNA-binding specificity and have similar transcriptional activation properties. In this article, we describe the cDNA cloning and characterization of the murine TEA proteins DTEF-1 (mDTEF-1) and ETF. Using in situ hybridization analysis of mouse embryos, we found that mDTEF-1 and ETF transcript distributions substantially overlap. ETF is expressed throughout the embryo except in the myocardium early in development, whereas late in development, it is enriched in lung and neuroectoderm. Mouse DTEF-1 is expressed at a much lower level throughout development and is substantially enriched in ectoderm and skin, as well as in the developing pituitary at midgestation. Northern blot analysis of adult mouse tissue total RNA showed that both ETF and mDTEF-1 are abundant in uterus and lung relative to other tissues. Using gel mobility shift assays and GAL4-fusion protein analysis, we demonstrated that the full coding sequences of ETF and mDTEF-1 encode M-CAT/GT-IIC-binding proteins containing activation domains.

  19. Characterization of a Cryopreserved Split-Thickness Human Skin Allograft-TheraSkin.

    Science.gov (United States)

    Landsman, Adam; Rosines, Eran; Houck, Amanda; Murchison, Angela; Jones, Alyce; Qin, Xiaofei; Chen, Silvia; Landsman, Arnold R

    2016-09-01

    The purpose of this study was to examine the characteristics of a cryopreserved split-thickness skin allograft produced from donated human skin and compare it with fresh, unprocessed human split-thickness skin. Cutaneous wound healing is a complex and organized process, where the body re-establishes the integrity of the injured tissue. However, chronic wounds, such as diabetic or venous stasis ulcers, are difficult to manage and often require advanced biologics to facilitate healing. An ideal wound care product is able to directly influence wound healing by introducing biocompatible extracellular matrices, growth factors, and viable cells to the wound bed. TheraSkin (processed by LifeNet Health, Virginia Beach, Virginia, and distributed by Soluble Systems, Newport News, Virginia) is a minimally manipulated, cryopreserved split-thickness human skin allograft, which contains natural extracellular matrices, native growth factors, and viable cells. The authors characterized TheraSkin in terms of the collagen and growth factor composition using ELISA, percentage of apoptotic cells using TUNEL analysis, and cellular viability using alamarBlue assay (Thermo Fisher Scientific, Waltham, Massachusetts), and compared these characteristics with fresh, unprocessed human split-thickness skin. It was found that the amount of the type I and type III collagen, as well as the ratio of type I to type III collagen in TheraSkin, is equivalent to fresh unprocessed human split-thickness skin. Similar quantities of vascular endothelial growth factor, insulinlike growth factor 1, fibroblast growth factor 2, and transforming growth factor β1 were detected in TheraSkin and fresh human skin. The average percent of apoptotic cells was 34.3% and 3.1% for TheraSkin and fresh skin, respectively. Cellular viability was demonstrated in both TheraSkin and fresh skin.

  20. DMPD: Toll-like receptor 9 in murine lupus: more friend than foe! [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18241699 Toll-like receptor 9 in murine lupus: more friend than foe! Yu P, Musette ...us: more friend than foe! PubmedID 18241699 Title Toll-like receptor 9 in murine lupus...P, Peng SL. Immunobiology. 2008;213(2):151-7. Epub 2007 Sep 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptor 9 in murine lup

  1. Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes: smooth dogfish (Mustelus canis), sandbar shark (Carcharhinus plumbeus), and clearnose skate (Raja eglanteria).

    Science.gov (United States)

    Larsen, Julie; Bushnell, Peter; Steffensen, John; Pedersen, Morten; Qvortrup, Klaus; Brill, Richard

    2017-02-01

    We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca 2+ release from the sarcoplasmic reticulum (SR) with ryanodine and thapsigargin and measuring the resultant changes in contraction-relaxation parameters and the force-frequency relationship at 20 °C and 30 °C. We also examined ultrastructural differences with electron microscopy. In tissues from smooth dogfish, net force (per cross-sectional area) and measures of the speeds of contraction and relaxation were all higher in atrial than ventricular myocardium at both temperatures. Atrial-ventricular differences were evident in the other two species primarily in measures of the rates of contraction and relaxation. Ryanodine-thapsigargin treatment reduced net force and its maximum positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark at 30 °C; indicating that SR involvement in excitation-contraction (EC) coupling is species- and temperature-specific in elasmobranch fishes, as it is in teleost fishes. Atrial and ventricular myocardium from all three species displayed a negative force-frequency relationship, but there was no evidence that SR involvement in EC coupling was influenced by heart rate. SR was evident in electron micrographs, generally located in proximity to mitochondria and intercalated discs, and to a lesser extent between the myofibrils; with mitochondria being more numerous in ventricular than atrial myocardium in all three species.

  2. Application of water-assisted ultraviolet light processing on the inactivation of murine norovirus on blueberries.

    Science.gov (United States)

    Liu, Chuhan; Li, Xinhui; Chen, Haiqiang

    2015-12-02

    In this study, a novel set-up using water-assisted UV processing was developed and evaluated for its decontamination efficacy against murine norovirus (MNV-1) inoculated on fresh blueberries for both small and large-scale experimental setups. Blueberries were skin-inoculated with MNV-1 and treated for 1-5 min with UV directly (dry UV) or immersed in agitated water during UV treatment (water-assisted UV). The effect of the presence of 2% (v/v) blueberry juice or 5% crushed blueberries (w/w) in wash water was also evaluated. Results showed that water-assisted UV treatment generally showed higher efficacies than dry UV treatment. With 12,000 J/m(2) UV treatment in small-scale setup, MNV reductions of >4.32- and 2.48-log were achieved by water-assisted UV and dry UV treatments, respectively. Water-assisted UV showed similar inactivating efficacy as 10-ppm chlorine wash. No virus was detected in wash water after UV treatment or chlorine wash. MNV-1 was more easily killed on skin-inoculated blueberries compared with calyx-inoculated berries. When clear water was used as wash water in the large-scale setup, water-assisted UV treatment (UV dose of 12,000 J/m(2)) resulted in >3.20 log and 1.81 log MNV-1 reductions for skin- and calyx-inoculated berries, respectively. The presence of 2% blueberry juice in wash water decreased the decontamination efficacy of water-assisted UV and chlorine washing treatments. To improve the inactivation efficacy, the effect of combining water-assisted UV treatment with chlorine washing was also evaluated. The combined treatment had better or similar inactivation efficacy compared to water-assisted UV treatment and chlorine washing alone. Findings of this study suggest that water-assisted UV treatment could be used as an alternative to chlorine washing for blueberries and potentially for other fresh produce. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Skin Cancer Treatment

    Science.gov (United States)

    ... Unusual Cancers of Childhood Treatment Genetics of Skin Cancer Skin color and being exposed to sunlight can increase ... is based on the type of nonmelanoma skin cancer or other skin condition diagnosed: Basal cell carcinoma Enlarge Basal cell ...

  4. Fatty acid uptake in normal human myocardium

    International Nuclear Information System (INIS)

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R.

    1991-01-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 ± 0.024 mumol/g and 0.37 ± 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells

  5. Skin friction: a novel approach to measuring in vivo human skin

    OpenAIRE

    Veijgen, N.K.

    2013-01-01

    The human skin plays an important role in people’s lives. It is in constant interaction with the environment, clothing and consumer products. This thesis discusses one of the parameters in the interaction between the human skin in vivo and other materials: skin friction. The thesis is divided into three parts. The first part is an introduction to skin friction and to current knowledge on skin friction. The second part presents the RevoltST, the tribometer that was specially developed for skin...

  6. Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions

    International Nuclear Information System (INIS)

    Ando, Koichi; Koike, Sachiko; Uzawa, Akiko; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Aoki, Mizuho; Hirayama, Ryoichi

    2006-01-01

    In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-linear energy transfer (LET) feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/μm carbon ions or γ rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using γ rays. For fractionated γ rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials. (author)

  7. [Skin-to-skin caesarean section: a hype or better patient care?

    Science.gov (United States)

    Korteweg, F J; de Boer, H D; van der Ploeg, J M; Buiter, H D; van der Ham, D P

    2017-01-01

    A caesarean section (CS) is one of the most common surgical procedures performed in the world, for which there are minimal variations in the surgical approach. During the last few years the "skin-to-skin" CS, also coined "natural" or "gentle" CS, is on the rise; parental participation, slow delivery and direct skin-to-skin contact are important aspects. Most Dutch hospitals offer some form of "skin-to-skin" CS but there are local differences in availability and performance of the procedure. Since 2011, the standard procedure in the Martini Hospital in Groningen is the "skin-to-skin" CS (for both elective and emergency CS, 24/7). We describe our method and share our retrospective data, and demonstrate that this procedure does not result in more complications for mother or baby.

  8. Biomechanical Properties of Murine Meniscus Surface via AFM-based Nanoindentation

    Science.gov (United States)

    Li, Qing; Doyran, Basak; Gamer, Laura W.; Lu, X. Lucas; Qin, Ling; Ortiz, Christine; Grodzinsky, Alan J.; Rosen, Vicki; Han, Lin

    2015-01-01

    This study aimed to quantify the biomechanical properties of murine meniscus surface. Atomic force microscopy (AFM)-based nanoindentation was performed on the central region, proximal side of menisci from 6- to 24-week old male C57BL/6 mice using microspherical tips (Rtip ≈ 5 μm) in PBS. A unique, linear correlation between indentation depth, D, and response force, F, was found on menisci from all age groups. This non-Hertzian behavior is likely due to the dominance of tensile resistance by the collagen fibril bundles on meniscus surface that are mostly aligned along the circumferential direction observed on 12-week old menisci. The indentation resistance was calculated as both the effective stiffness, Sind = dF/dD, and the effective modulus, Eind, via the isotropic Hertz model. Values of Sind and Eind were found to depend on indentation rate, suggesting the existence of poro-viscoelasticity. These values do not significantly vary with anatomical sites, lateral versus medial compartments, or mouse age. In addition, Eind of meniscus surface (e.g., 6.1 ± 0.8 MPa for 12 weeks of age, mean ± SEM, n = 13) was found to be significantly higher than those of meniscus surfaces in other species, and of murine articular cartilage surface (1.4 ± 0.1 MPa, n = 6). In summary, these results provided the first direct mechanical knowledge of murine knee meniscus tissues. We expect this understanding to serve as a mechanics-based benchmark for further probing the developmental biology and osteoarthritis symptoms of meniscus in various murine models. PMID:25817332

  9. Identification and enrichment of colony-forming cells from the adult murine pituitary

    International Nuclear Information System (INIS)

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q.

    2005-01-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, β-Ala-Lys-Nε-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA + cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA + population contains rare cells that are GH + or PRL + . GH + cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH + cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments

  10. Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of murine experimental models.

    Directory of Open Access Journals (Sweden)

    Daiane Figueiredo Rosa

    Full Text Available Chronic alcohol intake associated with an inappropriate diet can cause lesions in multiple organs and tissues and complicate the tissue repair process. In a systematic review, we analyzed the relevance of alcohol and high fat consumption to cutaneous and repair, compared the main methodologies used and the most important parameters tested. Preclinical investigations with murine models were assessed to analyze whether the current evidence support clinical trials.The studies were selected from MEDLINE/PubMed and Scopus databases, according to Fig 1. All 15 identified articles had their data extracted. The reporting bias was investigated according to the ARRIVE (Animal Research: Reporting of in Vivo Experiments strategy.In general, animals offered a high-fat diet and alcohol showed decreased cutaneous wound closure, delayed skin contraction, chronic inflammation and incomplete re-epithelialization.In further studies, standardized experimental design is needed to establish comparable study groups and advance the overall knowledge background, facilitating data translatability from animal models to human clinical conditions.

  11. Skin color independent assessment of aging using skin autofluorescence

    NARCIS (Netherlands)

    Koetsier, M.; Nur, Erfan; Chunmao, Han; Lutgers, Helen L.; Links, Thera P.; Smit, Andries J.; Rakhorst, Gerhard; Graaff, Reindert

    2010-01-01

    Skin autofluorescence (AF) for the non-invasive assessment of the amount of accumulated tissue Advanced Glycation Endproducts (AGEs) increases with aging. In subjects with darker skin colors, measurements typically result in lower AF values than in subjects with fair skin colors, e.g. due to

  12. Skin color independent assessment of aging using skin autofluorescence

    NARCIS (Netherlands)

    Koetsier, M.; Nur, E.; Chunmao, H.; Lutgers, H.L.; Links, T.P.; Smit, A.J.; Rakhorst, G.; de Graaff, R.

    2010-01-01

    Skin autofluorescence (AF) for the non-invasive assessment of the amount of accumulated tissue Advanced Glycation Endproducts (AGEs) increases with aging. In subjects with darker skin colors, measurements typically result in lower AF values than in subjects with fair skin colors, e. g. due to

  13. [Virulence of Sporothrix globosa in murine models].

    Science.gov (United States)

    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Supplementation with Eskimo Skin Care improves skin elasticity in women. A pilot study.

    Science.gov (United States)

    Segger, Dörte; Matthies, Andreas; Saldeen, Tom

    2008-01-01

    To investigate the question of whether supplementation with an oral oil formulation rich in natural stable fish oil can alter skin elasticity, transepidermal water loss (TEWL), and skin roughness in healthy women. Twenty-four healthy women aged 40-60 years participated in a single-blind randomized trial for testing the effect of a proprietary oral supplement for skin nutrition (Eskimo Skin Care) on skin elasticity, TEWL, and skin roughness. Skin elasticity was measured by an optical cutometer, TEWL by a water-loss module based upon the vapour gradient principle, and skin roughness with a three-dimensional microtopography imaging system. Skin elasticity increased by 10% after 3 months of treatment with the supplement, a statistically significant increase in comparison with the control group (p=0.0298). There was a trend, though not statistically significant, towards a positive influence on the skin's barrier function. No effect on the skin roughness was observed. Eskimo Skin Care, an oral preparation rich in natural stable fish oil, can improve skin elasticity.

  15. Enhanced detection and study of murine norovirus-1 using a more efficient microglial cell line

    Directory of Open Access Journals (Sweden)

    Lu Yuanan

    2009-11-01

    Full Text Available Abstract Background Human Noroviruses are the predominant cause of non-bacterial gastroenteritis worldwide. To facilitate prevention and control, a norovirus isolated from mice can provide a model to understand human noroviruses. To establish optimal viral infectivity conditions for murine noroviruses, several cell lines of hematopoietic lineage, including murine BV-2, RAW 264.7, and TIB, as well as human CHME-5, were tested comparatively for their sensitivity to murine norovirus-1. Results Except for CHME-5, all three murine-derived cell lines were susceptible to MNV infection. Viral infection of these cells was confirmed by RT-PCR. Using both viral plaque and replication assays, BV-2 and RAW 264.7 cells were determined to have comparable sensitivities to MNV-1 infection. Comparisons of cell growth characteristics, general laboratory handling and potential in-field applications suggest the use of BV-2 to be more advantageous. Conclusion Results obtained from these studies demonstrate that an immortalized microglial cell line can support MNV-1 replication and provides a more efficient method to detect and study murine noroviruses, facilitating future investigations using MNV-1 as a model to study, detect, and control Human Norovirus.

  16. Three-dimensional alginate spheroid culture system of murine osteosarcoma.

    Science.gov (United States)

    Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

    2009-11-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.

  17. Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

    International Nuclear Information System (INIS)

    Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

    2000-01-01

    Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

  18. Anti-oxidant defence mechanism in vitiliginous skin increases with skin type

    NARCIS (Netherlands)

    Briganti, S.; Caron-Schreinemachers, A.-L. D. B.; Picardo, M.; Westerhof, W.

    2012-01-01

    Background Vitiligo skin shows different burning capacity in people with different phototype. In normal skin antioxidant status is correlated to skin phototype, but unexpectedly it appears that there is a gradual decrease in burning susceptibility of depigmented skin of individuals with increasing

  19. Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.

    Science.gov (United States)

    Mondoulet, L; Dioszeghy, V; Ligouis, M; Dhelft, V; Dupont, C; Benhamou, P-H

    2010-04-01

    Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods. Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens. Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens. At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 microg/mL, 2.5 vs. 0.46 microg/mL, 0.39 vs. 0.05 microg/mL and 15.0 vs. 5.5 microg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05). In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies.

  20. Nutrition and skin.

    Science.gov (United States)

    Pappas, Apostolos; Liakou, Aikaterini; Zouboulis, Christos C

    2016-09-01

    Nutrition has long been associated with skin health, including all of its possible aspects from beauty to its integrity and even the aging process. Multiple pathways within skin biology are associated with the onset and clinical course of various common skin diseases, such as acne, atopic dermatitis, aging, or even photoprotection. These conditions have been shown to be critically affected by nutritional patterns and dietary interventions where well-documented studies have demonstrated beneficial effects of essential nutrients on impaired skin structural and functional integrity and have restored skin appearance and health. Although the subject could be vast, the intention of this review is to provide the most relevant and the most well-documented information on the role of nutrition in common skin conditions and its impact on skin biology.

  1. 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

    International Nuclear Information System (INIS)

    Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

    2002-01-01

    14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

  2. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  3. Azithromycin prophylaxis and treatment of murine toxoplasmosis.

    Science.gov (United States)

    Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

    2005-03-01

    To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

  4. Skin hydration, microrelief and greasiness of normal skin in Antarctica.

    Science.gov (United States)

    Tsankov, N; Mateev, D; Darlenski, R

    2018-03-01

    The skin is the primary defence of the human body against external factors from physical, chemical, mechanical and biologic origin. Climatic factors together with low temperature and sun radiation affect the skin. The effect of climatic conditions in Antarctica on healthy skin has not been previously addressed. The aim of this study was to evaluate the changes in the skin hydration, greasiness and microrelief due to the extreme climatic environmental factors during the stay of the members of the Bulgarian Antarctic expedition. Fifty-nine Caucasian healthy subjects, 42 men and 17 women with mean age 50.9 years (27-68), were enrolled. The study was performed in five consecutive years from 2011 to 2016 at the Bulgarian Antarctic base camp at Livingston Island. The study protocol consisted of two parts: study A: duration of 15 days with measurement of skin physiology parameters on a daily basis, and study B: five measurements at baseline and at days 14, 30, 45 and 50 upon arrival in Antarctica. We measured three biophysical parameters related to skin physiology at cheek skin by an impedance measuring device. No statistically significant difference between parameters at the different measurement points. There is a variation in skin hydration reaching its lower point at day 11 and then returning to values similar to baseline. Initially, an increase in skin greasiness was witnessed with a sharp depression at day 11 and final values at day 15 resembling the ones at baseline. An increase, although not statistically significant, in skin roughness was observed in the first 15 days of the study. Study B showed no statistically significant variances between values of the three parameters. Our studies show the pioneer results of the effect of Antarctic climate on human skin physiology. © 2017 European Academy of Dermatology and Venereology.

  5. Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy.

    Science.gov (United States)

    Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

    2018-03-01

    A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

  6. A review of patient and skin characteristics associated with skin tears.

    Science.gov (United States)

    Rayner, R; Carville, K; Leslie, G; Roberts, P

    2015-09-01

    Skin tears are the most common wound among the elderly and have the potential to cause infection, form chronic wounds, reduce quality of life and increase health-care costs. Our aim was to identify studies that reviewed patient and skin characteristics associated with skin tears. A review of skin tear studies reported in the English literature between 1980 and 2013 was undertaken using the following electronic databases: PubMed, Medline, CINAHL, Embase, Scopus, Evidence Based and Medicine Reviews (EBM). Search terms included aged, skin, tears or lacerations, skin tearing, geri tear, epidermal tear and prevalence. There were 343 articles found with using the search terms. After abstract review nine were found to be relevant to the search. The principle findings from these eight published articles and one unpublished study revealed that the most common patient characteristics were a history of skin tears, impaired mobility and impaired cognition. Skin characteristics associated with skin tears included senile purpura, ecchymosis and oedema. This review provides an overview of identified patient and skin characteristics that predispose the elderly to skin tears and exposes the lack of research within this domain. R. Rayner is a recipient of a 2013 Australian Postgraduate Award, Curtin University Postgraduate Scholarship and a Wound Management Cooperative Research Centre (CRC) PhD stipend. The School of Nursing, Midwifery and Paramedicine, Curtin University and the Silver Chain Group, Western Australia are participants in the Wound Management Innovation CRC. No conflict of interest exists among the authors.

  7. Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide.

    Science.gov (United States)

    Mzhelskaya, M M; Klinnikova, M G; Koldysheva, E V; Lushnikova, E L

    2017-10-01

    The expression of VEGFR2 (Flk-1, according to immunohistochemistry) and of cyclin D2 mRNA (according to real-time PCR) in the myocardium of rats is studied in doxorubicin-induced cardiomyopathy and in response to betulonic acid amide. Doxorubicin alone and in combination with betulonic acid amide causes after 3 days a manifest reduction of cyclin D2 mRNA expression (by 38 and 63%, respectively), while injection of betulonic acid amide alone causes a 23-fold increase of cyclin D2 mRNA expression. An increase of cyclin D2 mRNA expression has been detected in all experimental groups after 14 days of experiment, the most pronounced in response to betulonic acid amide (63 times). The expression of Flk-1 in cardiomyocytes increases significantly in response to both chemical agents starting from day 3 of experiment. These results indicate that doxorubicin and betulonic acid amide induce cytoprotective reactions in the myocardium, first at the intracellular, then at the cellular levels.

  8. Inflammatory microenvironment and tumor necrosis factor alpha as modulators of periostin and CCN2 expression in human non-healing skin wounds and dermal fibroblasts.

    Science.gov (United States)

    Elliott, Christopher G; Forbes, Thomas L; Leask, Andrew; Hamilton, Douglas W

    2015-04-01

    Non-healing skin wounds remain a significant clinical burden, and in recent years, the regulatory role of matricellular proteins in skin healing has received significant attention. Periostin and CCN2 are both upregulated at day 3 post-wounding in murine skin, where they regulate aspects of the proliferative phase of repair including mesenchymal cell infiltration and myofibroblast differentiation. In this study, we examined 1) the wound phenotype and expression patterns of periostin and CCN2 in non-healing skin wounds in humans and 2) the regulation of their expression in wound fibroblasts by tumor necrosis factor α (TNFα) and transforming growth factor-β1 (TGF-β1). Chronic skin wounds had a pro-inflammatory phenotype, characterized by macrophage infiltration, TNFα immunoreactivity, and neutrophil infiltration. Periostin, but not CCN2, was significantly suppressed in non-healing wound edge tissue at the mRNA and protein level compared with non-involved skin. In vitro, human wound edge fibroblasts populations were still able to proliferate and contract collagen gels. Compared to cells from non-involved skin, periostin and α-SMA mRNA levels increased significantly in the presence of TGF-β1 in wound cells and were significantly decreased by TNFα, but not those of Col1A2 or CCN2. In the presence of both TGF-β1 and TNFα, periostin and α-SMA mRNA levels were significantly reduced compared to TGF-β1 treated wound cells. Effects of TGF-β1 and TNFα on gene expression were also more pronounced in wound edge cells compared to non-involved fibroblasts. We conclude that variations in the expression of periostin and CCN2, are related to an inflammatory microenvironment and the presence of TNFα in human chronic wounds. Copyright © 2015. Published by Elsevier B.V.

  9. Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy

    Directory of Open Access Journals (Sweden)

    Ralph Verstappen

    2018-03-01

    Full Text Available Background A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. Methods All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. Results We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. Conclusions In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

  10. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

    Directory of Open Access Journals (Sweden)

    Carolina N Perdigoto

    2016-07-01

    Full Text Available An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2 in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

  11. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

    Science.gov (United States)

    Perdigoto, Carolina N; Dauber, Katherine L; Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J; Cohen, Idan; Santoriello, Francis J; Zhao, Dejian; Zheng, Deyou; Hsu, Ya-Chieh; Ezhkova, Elena

    2016-07-01

    An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

  12. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R. (Univ. of Utah School of Medicine, Salt Lake City (USA))

    1991-04-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

  13. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

    International Nuclear Information System (INIS)

    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R.

    1991-01-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function

  14. Chimeric anti-tenascin antibody 81C6: Increased tumor localization compared with its murine parent

    International Nuclear Information System (INIS)

    Zalutsky, Michael R.; Archer, Gary E.; Garg, Pradeep K.; Batra, Surinder K.; Bigner, Darell D.

    1996-01-01

    When labeled using the Iodogen method, a chimeric antibody composed of the human IgG 2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6

  15. Subcellular localization and photodynamic activity of Photodithazine (glucosamine salt of chlorin e6) in murine melanoma B16-F10: an in vitro and in vivo study

    Science.gov (United States)

    Ono, Bruno Andrade; Pires, Layla; Nogueira, Marcelo Saito; Kurachi, Cristina; Pratavieira, Sebastião.

    2018-02-01

    Photodynamic therapy (PDT) is already a good option for the clinical treatment of several lesions, including mainly nonmelanoma skin cancers. However, cutaneous melanoma treatment remains a challenge when using PDT. One of the reasons for its reduced efficacy is the high pigmentation of melanoma cells. The object of our study is to evaluate the feasibility of the Photodithazine as a photosensitizer for melanoma. Photodithazine is already used in some malignant tumors with satisfactory results and has significant absorption band around 660 nm where the absorption of melanin is low. In this study, we measured the subcellular localization and photodynamic activity of Photodithazine (PDZ) in murine melanoma B16-F10 cell culture. Additionally, a PDT procedure was applied in an animal melanoma model. This first result demonstrates that Photodithazine is more localized at mitochondria in B16F10 cell culture and the cell viability is reduced to less than 90% using 1 µg/mL (PDZ) and 2 J/cm2. We also noticed a rapid PDZ (less than one hour) accumulation in a murine melanoma model. The treatment of melanoma resulted in 20 % more animal survival after one session of PDT compared with the control group. More studies are required to evaluate the cytotoxic effects of Photodithazine at human melanoma.

  16. Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

    Science.gov (United States)

    Takeyoshi, Masahiro; Noda, Shuji; Yamazaki, Shunsuke; Kakishima, Hiroshi; Yamasaki, Kanji; Kimber, Ian

    2004-01-01

    Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. Copyright 2004 John Wiley & Sons, Ltd.

  17. SKIN CARE IN INFANTS

    Directory of Open Access Journals (Sweden)

    I. N. Zakharova

    2014-01-01

    Full Text Available Human skin is a complex organ in its structure. Numerous functions of the skin may be impaired in its pathology. Anatomical and physiological characteristics of the skin in children predispose to common diseases of the skin. Diaper dermatitis is one of the most common skin diseases during infancy and childhood. Diapered skin is exposed to friction and excessive hydration, has a higher pH than nondiapered skin, and is repeatedly soiled with feces that contains enzymes with high irritation potential for the skin. Diaper dermatitis may vary in clinical severity and course. Therapeutically, frequent diaper changes and adequate skin care are most important. Appropriate skin care can help to prevent the occurrence of diaper dermatitis and to speed up the healing of affected skin. This includes frequent diaper changes and aeration, gentle cleansing, and the use of a barrier cream. For the treatment of diaper dermatitis agents selected depending on the presence and severity of complications. For prevention and treatment of uncomplicated diaper dermatitis effective means of containing dexpantenol.

  18. Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

    Science.gov (United States)

    Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

    1978-02-28

    The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

  19. /sup 31/P-NMR studies of respiratory regulation in the intact myocardium

    Energy Technology Data Exchange (ETDEWEB)

    From, A H.L.; Petein, M A; Zimmer, S W; Michurski, S P; Ugurbil, K

    1986-10-06

    The mechanism by which mitochondrial respiration is coupled to ATP consumption in intact tissues is unclear. The authors determined the relationship between high-energy phosphate levels and oxygen consumption rate in rat hearts operating over a range of workloads and perfused with different substrates. With pyruvate + glucose perfusion, ADP levels were in general very low, and varied with MVO/sub 2/ yielding an apparent K/sub m/ of 25 +- 5 ..mu..M, suggesting regulation of oxidative phosphorylation through availability of ADP. In contrast, with glucose perfusion in the presence or absence of insulin, ADP levels, ADP/ATP ratio or the phosphate potential were relatively constant over the workload range examined and generally not correlated with alterations in MVO/sub 2/; it is suggested that under these conditions, carbon substrate delivery to the mitochondria may control mitochondrial respiration. The common feature of both of the suggested regulatory mechanisms is substrate limitation which, however, is exercised at different metabolic points depending on the carbon substrate available to the myocardium. 19 refs.; 2 figs.; 1 table.

  20. Novel Application of Micro-Computerized Tomography for Morphologic Characterization of the Murine Penis.

    Science.gov (United States)

    O'Neill, Marisol; Huang, Gene O; Lamb, Dolores J

    2017-12-01

    The murine penis model has enriched our understanding of anomalous penile development. The morphologic characterization of the murine penis using conventional serial sectioning methods is labor intensive and prone to errors. To develop a novel application of micro-computerized tomography (micro-CT) with iodine staining for rapid, non-destructive morphologic study of murine penis structure. Penises were dissected from 10 adult wild-type mice and imaged using micro-CT with iodine staining. Images were acquired at 5-μm spatial resolution on a Bruker SkyScan 1272 micro-CT system. After images were acquired, the specimens were washed of any remaining iodine and embedded in paraffin for conventional histologic examination. Histologic and micro-CT measurements for all specimens were made by 2 independent observers. Measurements of penile structures were made on virtual micro-CT sections and histologic slides. The Lin concordance correlation coefficient demonstrated almost perfect strength of agreement for interobserver variability for histologic section (0.9995, 95% CI = 0.9990-0.9997) and micro-CT section (0.9982, 95% CI = 0.9963-0.9991) measurements. Bland-Altman analysis for agreement between the 2 modalities of measurement demonstrated mean differences of -0.029, 0.022, and -0.068 mm for male urogenital mating protuberance, baculum, and penile glans length, respectively. There did not appear to be a bias for overestimation or underestimation of measured lengths and limits of agreement were narrow. The enhanced ability offered by micro-CT to phenotype the murine penis has the potential to improve translational studies examining the molecular pathways contributing to anomalous penile development. The present study describes the first reported use of micro-CT with iodine staining for imaging the murine penis. Producing repeated histologic sections of identical orientation was limited by inherent imperfections in mounting and tissue sectioning, but this was

  1. Non-ablative skin tightening with radiofrequency in Asian skin.

    Science.gov (United States)

    Kushikata, Nobuharu; Negishi, Kei; Tezuka, Yukiko; Takeuchi, Kaori; Wakamatsu, Shingo

    2005-02-01

    The recent successful application of radiofrequency (RF) in non-ablative skin tightening for skin laxity has attracted attention worldwide. The efficacy and clinical effect of RF were assessed in Asian skin, with additional study on the duration of the effect and any complications. Eighty-five Japanese females were enrolled in the study for treatment of nasolabial folds, marionette lines, and sagging jowls with 6-month follow-up. RF treatment was effective for nasolabial folds, marionette lines, and jowls. Objective physician evaluation found relatively good improvement at 3 months post-treatment, and even better improvement at the 6-month evaluation. RF treatment was very satisfactory for skin tightening in Asian facial skin. When compared with published literature from the United States, the results suggested that there might be race-related differences in the treatment parameters. (c) 2005 Wiley-Liss, Inc.

  2. Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

    Science.gov (United States)

    Wondrak, Georg T; Jacobson, Myron K; Jacobson, Elaine L

    2006-02-01

    Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.

  3. Histoplasma skin test

    Science.gov (United States)

    Histoplasmosis skin test ... health care provider cleans an area of your skin, usually the forearm. An allergen is injected just below the cleaned skin surface. An allergen is a substance that causes ...

  4. Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

    African Journals Online (AJOL)

    NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan. Abstract. Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni.

  5. Skin color - patchy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003224.htm Skin color - patchy To use the sharing features on this page, please enable JavaScript. Patchy skin color is areas where the skin color is irregular. ...

  6. 14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Takala, Teemu O.; Nuutila, Pirjo [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Department of Medicine, University of Turku (Finland); Pulkki, Kari [Department of Clinical Chemistry, University of Turku (Finland); Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Savunen, Timo; Vaehaesilta, Tommi [Department of Surgery, University of Turku (Finland); Luotolahti, Matti [Department of Clinical Physiology, University of Turku (Finland); Kallajoki, Markku [Department of Pathology, University of Turku (Finland)

    2002-12-01

    14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid ([{sup 18}F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [{sup 18}F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [{sup 18}F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [{sup 18}F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [{sup 18}F]FTHA metabolite analysis. Fractional [{sup 18}F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring {sup 18}F in the tissue samples. Fractional [{sup 18}F]FTHA uptake rates based on the analysis of tissue samples were 0.56{+-}0.17 ml g{sup -1} min{sup -1} and 0.037{+-}0.007 ml g{sup -1} min{sup -1} for myocardium and skeletal muscle (mean {+-} SD), respectively. The myocardial results obtained from the PET data (0.50{+-}0.11 ml g{sup -1} min{sup -1}) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%{+-}23% (mean{+-}SD, n=7) of the {sup 18}F entered mitochondria in myocardium, as compared with only 36%{+-}15% (mean{+-}SD, n=7) in skeletal muscle. Intracellular [{sup 18}F]FTHA metabolite analysis showed that a major part of [{sup 18}F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [{sup 18}F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [{sup 18}F]FTHA traces FFA beta-oxidation in the heart

  7. 1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

    International Nuclear Information System (INIS)

    Chattopadhyay, Kausik; Ramagopal, Udupi A.; Nathenson, Stanley G.; Almo, Steven C.

    2009-01-01

    1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL

  8. 1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, Kausik [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Ramagopal, Udupi A. [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Nathenson, Stanley G., E-mail: nathenso@aecom.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Almo, Steven C., E-mail: nathenso@aecom.yu.edu [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2009-05-01

    1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL.

  9. Skin Condition Finder

    Science.gov (United States)

    ... SKIN CONDITIONS HEALTH TOPICS FOR PROFESSIONALS Rash and Skin Condition Finder 1 Select Age Group Infant Child ... Toe Toe Webspace Toe Nail CLOSE About the Skin Condition Finder Have a health question or concern? ...

  10. Skin decontamination

    International Nuclear Information System (INIS)

    Moehrle, G.

    1975-01-01

    A general survey of skin decontamination is given. The success of every decontamination treatments depends mainly on the speed, but also on the care, with which the action is taken. The best way to remove the skin contaminants is thorough washing under lukewarm running water with mild soap and a soft brush. This washing is to be repeated several times for a period of several minutes. If results are not satisfactory, light duty detergents and wetting agents available commercially may also be used. Some solutions which have proved useful are mentioned. The decontamination solutions are best used in the order given. When one has no satisfactory decontamination effect, the next one is to be used. If necessary, these agents must be used several times in the stated order as long as this does not involve too much strain for the skin. All the decontamination measures mentioned refer, of course, to intact healthy skin. After decontamination has been completed, the skin should be treated with a protective cream

  11. Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

    Science.gov (United States)

    Yotsu, Rie Roselyne; Kouadio, Kouamé; Vagamon, Bamba; N'guessan, Konan; Akpa, Amari Jules; Yao, Aubin; Aké, Julien; Abbet Abbet, Rigobert; Tchamba Agbor Agbor, Barbine; Bedimo, Roger; Ishii, Norihisa; Fuller, L Claire; Hay, Roderick; Mitjà, Oriol; Drechsler, Henning; Asiedu, Kingsley

    2018-05-01

    Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process. We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary. Of a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3-26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance. We carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d'Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned

  12. Collagen-based silver nanoparticles: Study on cell viability, skin permeation, and swelling inhibition

    International Nuclear Information System (INIS)

    Saura Cardoso, Vinicius; Carvalho Filgueiras, Marcelo de; Medeiros Dutra, Yago; Gomes Teles, Ramon Handerson; Rodrigues de Araújo, Alyne; Primo, Fernando Lucas; Mafud, Ana Carolina; Batista, Larissa Fernandes; Mascarenhas, Yvonne Primerano

    2017-01-01

    Collagen is considered the most abundant protein in the animal kingdom, comprising 30% of the total amount of proteins and 6% of the human body by weight. Studies that examine the interaction between silver nanoparticles and proteins have been highlighted in the literature in order to understand the stability of the nanoparticle system, the effects observed in biological systems, and the appearance of new chemical pharmaceutical products. The objective of this study was to analyze the behavior of silver nanoparticles stabilized with collagen (AgNPcol) and to check the skin permeation capacity and action in paw edema induced by carrageenan. AgNPcol synthesis was carried out using solutions of reducing agent sodium borohydride (NaBH 4 ), silver nitrate (AgNO 3 ) and collagen. Characterization was done by using dynamic light scattering (DLS) and X-ray diffraction (XRD) and AFM. Cellular viability testing was performed by using flow cytometry in human melanoma cancer (MV3) and murine fibroblast (L929) cells. The skin permeation study was conducted using a Franz diffusion cell, and the efficiency of AgNPcol against the formation of paw edema in mice was evaluated. The hydrodynamic diameter and zeta potential of AgNPcol were 140.7 ± 7.8 nm and 20.1 ± 0.7 mV, respectively. AgNPcol failed to induce early apoptosis, late apoptosis, and necrosis in L929 cells; however, it exhibited enhanced toxicity in cancer cells (MV3) compared to normal cells (L929). AgNPcol demonstrated increased toxicological effects in cancer MV3 cells, promoting skin permeation, and preventing paw edema. - Highlights: • Silver nanoparticles were synthesized with type I collagen (AgNPcol). • AgNPcol which was characterized by XRD and DLS. • AgNPcol exhibited enhanced toxicity in cancer cells. • The efficiency of the AgNPcol against the paw edema was evaluated.

  13. Collagen-based silver nanoparticles: Study on cell viability, skin permeation, and swelling inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Saura Cardoso, Vinicius, E-mail: vscfisio@ufpi.edu.br [Research Center in Biodiversity and Biotechnology, Biotec, Campus Ministro Reis Velloso, Federal University of Piauí, UFPI, 64202020 Parnaíba, Piauí (Brazil); Physiotherapy Department, Campus Ministro Reis Velloso, Federal University of Piauí, UFPI, 64202020 Parnaíba, Piauí (Brazil); Carvalho Filgueiras, Marcelo de; Medeiros Dutra, Yago; Gomes Teles, Ramon Handerson [Physiotherapy Department, Campus Ministro Reis Velloso, Federal University of Piauí, UFPI, 64202020 Parnaíba, Piauí (Brazil); Morphology and Muscle Physiology Laboratory, LAMFIM, Campus Ministro Reis Velloso, Federal University of Piauí, UFPI, 64202020 Parnaíba, Piauí (Brazil); Rodrigues de Araújo, Alyne [Research Center in Biodiversity and Biotechnology, Biotec, Campus Ministro Reis Velloso, Federal University of Piauí, UFPI, 64202020 Parnaíba, Piauí (Brazil); Primo, Fernando Lucas [Faculdade de Ciências Farmacêuticas, UNESP, Universidade Estadual Paulista, Campus de Araraquara, Departamento de Bioprocessos e Biotecnologia, 14800903 Araraquara, São Paulo (Brazil); Mafud, Ana Carolina; Batista, Larissa Fernandes; Mascarenhas, Yvonne Primerano [Institute of Physics of São Carlos, IFSC, University of São Paulo, USP, 13566590 São Carlos, SP (Brazil); and others

    2017-05-01

    Collagen is considered the most abundant protein in the animal kingdom, comprising 30% of the total amount of proteins and 6% of the human body by weight. Studies that examine the interaction between silver nanoparticles and proteins have been highlighted in the literature in order to understand the stability of the nanoparticle system, the effects observed in biological systems, and the appearance of new chemical pharmaceutical products. The objective of this study was to analyze the behavior of silver nanoparticles stabilized with collagen (AgNPcol) and to check the skin permeation capacity and action in paw edema induced by carrageenan. AgNPcol synthesis was carried out using solutions of reducing agent sodium borohydride (NaBH{sub 4}), silver nitrate (AgNO{sub 3}) and collagen. Characterization was done by using dynamic light scattering (DLS) and X-ray diffraction (XRD) and AFM. Cellular viability testing was performed by using flow cytometry in human melanoma cancer (MV3) and murine fibroblast (L929) cells. The skin permeation study was conducted using a Franz diffusion cell, and the efficiency of AgNPcol against the formation of paw edema in mice was evaluated. The hydrodynamic diameter and zeta potential of AgNPcol were 140.7 ± 7.8 nm and 20.1 ± 0.7 mV, respectively. AgNPcol failed to induce early apoptosis, late apoptosis, and necrosis in L929 cells; however, it exhibited enhanced toxicity in cancer cells (MV3) compared to normal cells (L929). AgNPcol demonstrated increased toxicological effects in cancer MV3 cells, promoting skin permeation, and preventing paw edema. - Highlights: • Silver nanoparticles were synthesized with type I collagen (AgNPcol). • AgNPcol which was characterized by XRD and DLS. • AgNPcol exhibited enhanced toxicity in cancer cells. • The efficiency of the AgNPcol against the paw edema was evaluated.

  14. Skin Peeling Syndrome

    Directory of Open Access Journals (Sweden)

    Sharma Rajeev

    2000-01-01

    Full Text Available Peeling of the skin is an uncommonly encountered disorder. Occurrence of vesicles and bullae in peeling skin syndrome is very rare. We report a case of idiopathic peeling skin syndrome with vesicular lesions.

  15. Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

    1986-01-01

    The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

  16. Protective effects of astaxanthin from Paracoccus carotinifaciens on murine gastric ulcer models.

    Science.gov (United States)

    Murata, Kenta; Oyagi, Atsushi; Takahira, Dai; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Ishibashi, Takashi; Hara, Hideaki

    2012-08-01

    The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol- and acidified aspirin-induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

    DEFF Research Database (Denmark)

    Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan

    1998-01-01

    Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch...

  18. Human skin penetration of silver nanoparticles through intact and damaged skin

    International Nuclear Information System (INIS)

    Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

    2009-01-01

    There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm 2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm -2 (range -2 (range 0.43-11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62 ± 0.2 ng cm -2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

  19. The Relative Utility of Skin Resistance and Skin Conductance

    National Research Council Canada - National Science Library

    Barland, Gordon

    1990-01-01

    The effectiveness of two circuits (constant current = skin resistance; constant voltage = skin conductance) used for measuring electrodermal activity during a psychophysiological detection of deception...

  20. Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation.

    Science.gov (United States)

    Gimblet, Ciara; Meisel, Jacquelyn S; Loesche, Michael A; Cole, Stephen D; Horwinski, Joseph; Novais, Fernanda O; Misic, Ana M; Bradley, Charles W; Beiting, Daniel P; Rankin, Shelley C; Carvalho, Lucas P; Carvalho, Edgar M; Scott, Phillip; Grice, Elizabeth A

    2017-07-12

    Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Skin and antioxidants.

    Science.gov (United States)

    Poljsak, Borut; Dahmane, Raja; Godic, Aleksandar

    2013-04-01

    It is estimated that total sun exposure occurs non-intentionally in three quarters of our lifetimes. Our skin is exposed to majority of UV radiation during outdoor activities, e.g. walking, practicing sports, running, hiking, etc. and not when we are intentionally exposed to the sun on the beach. We rarely use sunscreens during those activities, or at least not as much and as regular as we should and are commonly prone to acute and chronic sun damage of the skin. The only protection of our skin is endogenous (synthesis of melanin and enzymatic antioxidants) and exogenous (antioxidants, which we consume from the food, like vitamins A, C, E, etc.). UV-induced photoaging of the skin becomes clinically evident with age, when endogenous antioxidative mechanisms and repair processes are not effective any more and actinic damage to the skin prevails. At this point it would be reasonable to ingest additional antioxidants and/or to apply them on the skin in topical preparations. We review endogenous and exogenous skin protection with antioxidants.

  2. Tumour suppression in skin and other tissues via cross-talk between vitamin D- and p53-signalling

    Directory of Open Access Journals (Sweden)

    Joerg eReichrath

    2014-06-01

    Full Text Available P53 and its family members have been implicated in the direct regulation of the vitamin D receptor (VDR. Vitamin D- and p53-signaling pathways have a significant impact on spontaneous or carcinogen-induced malignant transformation of cells, with VDR and p53 representing important tumour suppressors. VDR and the p53/p63/p73 proteins all function typically as receptors or sensors that turn into transcriptional regulators upon stimulus, with the main difference being that the nuclear VDR is activated as a transcription factor after binding its naturally occurring ligand 1,25-dihydroxyvitamin D with high affinity while the p53 family of transcription factors, mostly in the nucleoplasm, responds to a large number of alterations in cell homeostasis commonly referred to as stress. An increasing body of evidence now convincingly demonstrates a cross-talk between vitamin D- and p53-signaling that occurs at different levels, has genome-wide implications and that should be of high importance for many malignancies, including non-melanoma skin cancer. One interaction involves the ability of p53 to increase skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Pigmentation protects the skin against UV-induced DNA damage and skin carcinogenesis, yet on the other hand reduces cutaneous synthesis of vitamin D. A second level of interaction may be through the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression, and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute 2 (MDM2 gene in dependence of the presence of wild-type p53. MDM2 has a well established role as a key negative regulator of p53 activity

  3. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  4. Skin abscess

    Science.gov (United States)

    Abscess - skin; Cutaneous abscess; Subcutaneous abscess; MRSA - abscess; Staph infection - abscess ... Skin abscesses are common and affect people of all ages. They occur when an infection causes pus ...

  5. Anyone Can Get Skin Cancer

    Science.gov (United States)

    ... of Skin Cancer Skin Cancer Screening Research Anyone Can Get Skin Cancer Order the free Anyone Can ... rarely, younger children can develop skin cancer. How can people with dark skin get skin cancer? Although ...

  6. Cryotherapy - skin

    Science.gov (United States)

    Cryosurgery - skin; Warts - freezing; Warts - cryotherapy; Actinic keratosis - cryotherapy; Solar keratosis - cryotherapy ... may be used to: Remove warts Destroy precancerous skin lesions (actinic keratoses or solar keratoses) In rare ...

  7. Skin self-exam

    Science.gov (United States)

    Skin cancer - self-exam; Melanoma - self-exam; Basal cell cancer - self-exam; Squamous cell - self-exam; Skin mole - self-exam ... Checking your skin regularly can help you notice any unusual changes. Follow your health care provider's recommendations on how often to ...

  8. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

    2000-01-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

  9. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2000-12-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

  10. Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal.

    Science.gov (United States)

    Foster, April R; Nicu, Carina; Schneider, Marlon R; Hinde, Eleanor; Paus, Ralf

    2018-07-01

    In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF-DWAT interactions under conditions of wounding/stress.

  11. Stages of Skin Cancer

    Science.gov (United States)

    ... Unusual Cancers of Childhood Treatment Genetics of Skin Cancer Skin color and being exposed to sunlight can increase ... is based on the type of nonmelanoma skin cancer or other skin condition diagnosed: Basal cell carcinoma Enlarge Basal cell ...

  12. Chemical applicability domain of the local lymph node assay (LLNA) for skin sensitisation potency. Part 4. Quantitative correlation of LLNA potency with human potency.

    Science.gov (United States)

    Roberts, David W; Api, Anne Marie

    2018-07-01

    Prediction of skin sensitisation potential and potency by non-animal methods is the target of many active research programmes. Although the aim is to predict sensitisation potential and potency in humans, data from the murine local lymph node assay (LLNA) constitute much the largest source of quantitative data on in vivo skin sensitisation. The LLNA has been the preferred in vivo method for identification of skin sensitising chemicals and as such is potentially valuable as a benchmark for assessment of non-animal approaches. However, in common with all predictive test methods, the LLNA is subject to false positives and false negatives with an overall level of accuracy said variously to be approximately 80% or 90%. It is also necessary to consider the extent to which, for true positives, LLNA potency correlates with human potency. In this paper LLNA potency and human potency are compared so as to express quantitatively the correlation between them, and reasons for non-agreement between LLNA and human potency are analysed. This leads to a better definition of the applicability domain of the LLNA, within which LLNA data can be used confidently to predict human potency and as a benchmark to assess the performance of non-animal approaches. Copyright © 2018. Published by Elsevier Inc.

  13. Skin, Hair, and Nails

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Skin, Hair, and Nails KidsHealth / For Parents / Skin, Hair, and ... piel, el cabello y las uñas About Skin, Hair and Nails Skin is our largest organ. If ...

  14. Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

    Science.gov (United States)

    Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

    2016-04-01

    Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  15. Antigen-specific murine T cell clones produce soluble interleukin 2 receptor on stimulation with specific antigens

    International Nuclear Information System (INIS)

    Wagner, D.K.; York-Jolley, J.; Malek, T.R.; Berzofsky, J.A.; Nelson, D.L.

    1986-01-01

    In this study, monoclonal antibodies were used to the murine IL 2 receptor (IL 2R) termed 3C7 and 7D4, which bind to different epitopes on the murine IL 2R, to develop an ELISA to measure soluble murine IL 2R. Surprisingly, stimulated murine spleen cells not only expressed cell-associated IL 2R, but also produced a considerable level of cellfree IL 2R in the culture supernatant fluid. To assess the fine specificity of this response, myoglobin-immune murine T cell clones were stimulated with appropriate or inappropriate antigen and syngeneic or allogeneic presenting cells. Proliferation, measured by [ 3 H] thymidine incorporation, and levels of soluble IL 2R were determined at day 4. The production of soluble IL2R displayed the same epitope fine specificity, genetic restriction, and antigen dose-response as the proliferative response. Indeed, in some cases there was sharper discrimination of epitope specificity and genetic restriction with the soluble IL 2R levels. There was also reproducible clone-to-clone variation in the amount of soluble receptor produced in response to antigen among 12 T cell clones and lines tested. In time course experiments, proliferation was greatest at day 3, whereas soluble IL 2R levels continued to rise in subsequent days. To the authors' knowledge, this is the first demonstration of release of secretion of soluble IL 2R by murine T cells, and the first demonstration of the fine specificity and genetic restriction of the induction of soluble IL 2R by specific antigen

  16. Thermosensitive Hydrogel Mask Significantly Improves Skin Moisture and Skin Tone; Bilateral Clinical Trial

    Directory of Open Access Journals (Sweden)

    Anna Quattrone

    2017-06-01

    Full Text Available Objective: A temperature-sensitive state-changing hydrogel mask was used in this study. Once it comes into contact with the skin and reaches the body temperature, it uniformly and quickly releases the active compounds, which possess moisturizing, anti-oxidant, anti-inflammatory and regenerative properties. Methods: An open label clinical trial was conducted to evaluate the effects of the test product on skin hydration, skin tone and skin ageing. Subjects applied the product to one side of their face and underwent Corneometer® and Chromameter measurements, Visual assessment of facial skin ageing and facial photography. All assessments and Self-Perception Questionnaires (SPQ were performed at baseline, after the first application of the test product and after four applications. Results: After a single treatment we observed an increase in skin moisturisation, an improvement of skin tone/luminosity and a reduction in signs of ageing, all statistically significant. After four applications a further improvement in all measured parameters was recorded. These results were confirmed by the subjects’ own perceptions, as reported in the SPQ both after one and four applications. Conclusion: The hydrogel mask tested in this study is very effective in improving skin hydration, skin radiance and luminosity, in encouraging an even skin tone and in reducing skin pigmentation.

  17. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis.

    Directory of Open Access Journals (Sweden)

    Xavier Helluy

    Full Text Available Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis.Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast.This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of

  18. A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Ryan W Carroll

    Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

  19. Skin Picking Disorder

    Directory of Open Access Journals (Sweden)

    Pinar Cetinay Aydin

    2014-08-01

    Full Text Available Skin picking disorder is not a dermatological disorder and it is a table characterized with picking skin excessively and repetitively, leading to damage in skin tissue. Unlike normal picking behaviour, psychogenic skin picking is repetitive and it can lead to severe damage in the skin and even complications which constitute vital danger. While some patients define frequent but short lasting picking attacks, others define rarer attacks which last a few hours. Skin picking disorder, which is not included in the classification systems up to DSM-5 as a separate diagnosis category, is included as an independent diagnosis in Obsessive Compulsive Disorder and Associated Disorders category in DSM-5. In case reports, open label studies and double blind studies selective serotonin reuptake inhibitors are shown to be effective in the treatment of skin picking disorder. Mostly, cognitive-behaviourial techniques are used and have been proven to be useful in psychotherapy. Habit reversal is one of the behaviourial techniques which are frequently applied, give positive results in which well-being state can be maintained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 401-428

  20. The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

    Science.gov (United States)

    1995-04-13

    vaccinia virus-T7 RNA polymerase s y stem for e xpression of target genes . Mol . Cell . BioI . 7 : 2538-2544 . Gagneten , S ., Gout , 0 ., Dubois-Dalcq...glycoprotein. These results showed f or the first time that two murine CEA- related genes can be co-expressed in some cell lines from inbred mice...49 Southern Hybridization ................ . ............ 50 Subcloning of PCR Products and Gene Cloning ........ 51 Growth

  1. Skin bleaching: A neglected form of injury and threat to global skin ...

    African Journals Online (AJOL)

    Skin bleaching: A neglected form of injury and threat to global skin. JC Street, K Gaska, KM Lewis, ML Wilson. Abstract. Skin bleaching is the use of creams, gels, or soaps to lighten the skin and is known to cause a number of injuries, many of which are potentially life-threatening. Despite the growing body of research ...

  2. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-01-01

    Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

  3. Skin layer mechanics

    NARCIS (Netherlands)

    Geerligs, M.

    2010-01-01

    The human skin is composed of several layers, each with an unique structure and function. Knowledge about the mechanical behavior of these skin layers is important for clinical and cosmetic research, such as the development of personal care products and the understanding of skin diseases. Until

  4. Skin Biopsy

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... like these: skin rashes or conditions, such as eczema or psoriasis skin infections, such as staph diseases, ...

  5. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    Science.gov (United States)

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

    2017-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  7. Evaluation of sex-related changes in skin topography and structure using innovative skin testing equipment.

    Science.gov (United States)

    Dąbrowska, M; Mielcarek, A; Nowak, I

    2018-04-29

    Evaluation of skin condition on the basis of parametrization and objective measurements of the parameters has become obligatory. The aim of this study was to assess sex-related changes in skin topography and structure using the skin testing equipment. The study was carried out on the group of 40 volunteers (20 females and 20 males) of the mean age 24 ± 3 years. The skin parameters were measured using 3 devices: Visioscan ®  VC 98 (skin topography), Visioline ® VL 650 (skin macro relief) and Ultrascan UC22 (ultrasound imaging of the skin). All measurements were performed on the inner part of the left forearm. The skin parameters measured revealed significant differences in skin surface and structure between females and males. The skin of all women subjects was more homogenous in its structure with the presence of more abundant superficial skin lines and wrinkles in comparison to male skin. The higher number of skin furrows in the skin of women is in agreement with literature reports claiming that men's skin has lower number of wrinkles which are deeper and more pronounced. Ultrasound imaging of the skin indicated greater thickness and lower density of the dermis of men subjects compared to those of females. Non-invasive methods of skin testing using new and advanced equipment have provided a possibility of objective parametrization and evaluation of sex-related changes in skin topography and structure. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Sagging Skin

    Science.gov (United States)

    ... turkey neck,” this occurs as skin loses its elasticity and in cases where individuals have lost a ... technique or procedure is appropriate for my skin type? Did the doctor show me before-and-after ...

  9. Skin Complications

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Skin Complications Diabetes can affect every part of the ... lipoidica diabeticorum, diabetic blisters, and eruptive xanthomatosis. General Skin Conditions Bacterial Infections Several kinds of bacterial infections ...

  10. Skin Cancer

    Science.gov (United States)

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  11. Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model.

    Science.gov (United States)

    Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon; Kang, Hoon

    2016-10-01

    Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia.

  12. Skin-textile friction and skin elasticity in young and aged persons

    NARCIS (Netherlands)

    Gerhardt, L.C.; Lenz, A.; Spencer, N.D.; Munzer, T.; Derler, S.

    2009-01-01

    Background/purpose: The mechanical properties of human skin are known to change with ageing, rendering skin less resistant to friction and shear forces, as well as more vulnerable to wounds. Until now, only few and contradictory results on the age-dependent friction properties of skin have been

  13. Interaction of dermatologically relevant nanoparticles with skin cells and skin

    Directory of Open Access Journals (Sweden)

    Annika Vogt

    2014-12-01

    Full Text Available The investigation of nanoparticle interactions with tissues is complex. High levels of standardization, ideally testing of different material types in the same biological model, and combinations of sensitive imaging and detection methods are required. Here, we present our studies on nanoparticle interactions with skin, skin cells, and biological media. Silica, titanium dioxide and silver particles were chosen as representative examples for different types of skin exposure to nanomaterials, e.g., unintended environmental exposure (silica versus intended exposure through application of sunscreen (titanium dioxide or antiseptics (silver. Because each particle type exhibits specific physicochemical properties, we were able to apply different combinations of methods to examine skin penetration and cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical production were monitored on cells and in whole tissue samples. The combination of technologies and the joint discussion of results enabled us to look at nanoparticle–skin interactions and the biological relevance of our findings from different angles.

  14. Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg.

    Science.gov (United States)

    van de Vrugt, Henri J; Koomen, Mireille; Berns, Mariska A D; de Vries, Yne; Rooimans, Martin A; van der Weel, Laura; Blom, Eric; de Groot, Jan; Schepers, Rik J; Stone, Stacie; Hoatlin, Maureen E; Cheng, Ngan Ching; Joenje, Hans; Arwert, Fré

    2002-03-01

    Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder. Six distinct FA disease genes have been identified, the products of which function in an integrated pathway that is thought to support a nuclear caretaker function. Comparison of FA gene characteristics in different species may help to unravel the molecular function of the FA pathway. We have cloned the murine homologue of the Fanconi anaemia complementation group G gene, FANCG/XRCC9. The murine Fancg protein shows an 83% similarity to the human protein sequence, and has a predicted molecular weight of 68.5 kDa. Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity. At mRNA and protein levels we detected the co-expression of Fancg and Fanca in murine tissues. In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation. Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus. We identified a murine cDNA, Fancg, which cross-complements the cellular defect of human FA-G cells and thus represents a true homologue of human FANCG. Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment.

  15. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

    Directory of Open Access Journals (Sweden)

    Kuznitzky Raquel

    2004-04-01

    Full Text Available Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD. Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008, but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.

  16. Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies

    NARCIS (Netherlands)

    Yang, M.; Reese, J.; Cotecchia, S.; Michel, M. C.

    1998-01-01

    Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with

  17. Oily skin: an overview.

    Science.gov (United States)

    Sakuma, Thais H; Maibach, Howard I

    2012-01-01

    Oily skin (seborrhea) is a common cosmetic problem that occurs when oversized sebaceous glands produce excessive amounts of sebum giving the appearance of shiny and greasy skin. This paper overviews the main concepts of sebaceous gland anatomy and physiology, including the biosynthesis, storage and release of sebum, as well as its relationship to skin hydration and water barrier function. We also address how skin oiliness may vary according to diet, age, gender, ethnicity and hot humid climates. The deeper understanding of this skin type provides the opportunity to better guide patients regarding skin care and also assist in the development of sebosuppressive agents. Copyright © 2012 S. Karger AG, Basel.

  18. Risks of Skin Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of skin cancer. Skin cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about skin cancer: Skin Cancer Prevention Skin Cancer Treatment Melanoma Treatment Genetics ...

  19. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

  20. Clinical use of radiation sterile porcine skin and Ag-skin of porcine

    International Nuclear Information System (INIS)

    Zhu Xiaobo

    1995-01-01

    Clinical examination revealed that either radiation sterilized skin or Ag-skin of pig are effective biologic dressing. When used as temporary skin coverage for fresh burn wound, for wound after escharectomy, and for wounds among skin grafts, they are effective in preventing infection and loss of body fluid. They can also be used for covering the infected granulation wound to control bacterial growth and further contamination