WorldWideScience

Sample records for human grp94 protects

  1. The C-terminal domain of human grp94 protects the catalytic subunit of protein kinase CK2 (CK2alpha) against thermal aggregation. Role of disulfide bonds

    DEFF Research Database (Denmark)

    Roher, N; Miró, F; Boldyreff, B

    2001-01-01

    The C-terminal domain (residues 518-803) of the 94 kDa glucose regulated protein (grp94) was expressed in Escherichia coli as a fusion protein with a His6-N-terminal tag (grp94-CT). This truncated form of grp94 formed dimers and oligomers that could be dissociated into monomers by treatment...... ratios of 4 : 1. The presence of dithiothreitol markedly reduced the anti-aggregation effects of grp94-CT on CK2alpha without altering the solubility of the chaperone. It is concluded that the chaperone activity of the C-terminal domain of human grp94 requires the maintenance of its quaternary structure...... (dimers and oligomers), which seems to be stabilised by disulphide bonds....

  2. Structural Insights into Complexes of Glucose-Regulated Protein94 (Grp94) with Human Immunoglobulin G. Relevance for Grp94-IgG Complexes that Form In Vivo in Pathological Conditions

    Science.gov (United States)

    Pagetta, Andrea; Tramentozzi, Elisa; Tibaldi, Elena; Cendron, Laura; Zanotti, Giuseppe; Brunati, Anna Maria; Vitadello, Maurizio; Gorza, Luisa; Finotti, Paola

    2014-01-01

    While the mechanism by which Grp94 displays its chaperone function with client peptides in the cell has been elucidated extensively, much less is known about the nature and properties of how Grp94 can engage binding to proteins once it is exposed on the cell surface or liberated in the extra-cellular milieu, as occurs in pathological conditions. In this work, we wanted to investigate the molecular aspects and structural characteristics of complexes that Grp94 forms with human IgG, posing the attention on the influence that glycosylation of Grp94 might have on the binding capacity to IgG, and on the identification of sites involved in the binding. To this aim, we employed both native, fully glycosylated and partially glycosylated Grp94, and recombinant, non-glycosylated Grp94, as well as IgG subunits, in different experimental conditions, including the physiological setting of human plasma. Regardless of the species and type, Grp94 engages a similar, highly specific and stable binding with IgG that involves sites located in the N-terminal domain of Grp94 and the hinge region of whole IgG. Grp94 does not form stable complex with Fab, F(ab)2 or Fc. Glycosylation turns out to be an obstacle to the Grp94 binding to IgG, although this negative effect can be counteracted by ATP and spontaneously also disappears in time in a physiological setting of incubation. ATP does not affect at all the binding capacity of non-glycosylated Grp94. However, complexes that native, partially glycosylated Grp94 forms with IgG in the presence of ATP show strikingly different characteristics with respect to those formed in absence of ATP. Results have relevance for the mechanism regulating the formation of stable Grp94-IgG complexes in vivo, in the pathological conditions associated with the extra-cellular location of Grp94. PMID:24489700

  3. GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    2015-12-01

    Full Text Available Clearance of circulating low-density lipoprotein cholesterol (LDLc by hepatic LDL receptors (LDLR is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.

  4. Second Generation Grp94-Selective Inhibitors Provide Opportunities for the Inhibition of Metastatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Crowley, Vincent M. [Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Dr. Malott 4070 Lawrence KS 66045 USA; Huard, Dustin J. E. [School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta GA 30332 USA; Lieberman, Raquel L. [School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta GA 30332 USA; Blagg, Brian S. J. [Warren Family Research Center for Drug Discovery and Development, and Department of Chemistry & Biochemistry, University of Notre Dame, 305 McCourtney Hall Notre Dame IN 46556 USA

    2017-09-27

    Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum (ER) resident isoform of the 90 kDa heat shock protein (Hsp90) family and its inhibition represents a promising therapeutic target for the treatment of many diseases. Modification of the first generation cis-amide bioisostere imidazole to alter the angle between the resorcinol ring and the benzyl side chain via cis-amide replacements produced compounds with improved Grp94 affinity and selectivity. Structure–activity relationship studies led to the discovery of compound 30, which exhibits 540 nm affinity and 73-fold selectivity towards Grp94. Grp94 is responsible for the maturation and trafficking of proteins associated with cell signaling and motility, including select integrins. The Grp94-selective inhibitor 30 was shown to exhibit potent anti-migratory effects against multiple aggressive and metastatic cancers.

  5. Chronic lithium administration triggers an over-expression of GRP94 stress protein isoforms in mouse liver.

    Science.gov (United States)

    Nciri, R; Allagui, M S; Vincent, C; Murat, J C; Croute, F; El Feki, A

    2010-06-01

    Moderate doses of lithium were chronically administered to mice in order to verify whether the cytoprotective effects of lithium could be in part attributed to a molecular protection conferred by stress proteins/chaperones accumulation. In order to reach serum lithium levels within the common therapeutic values, mice were fed for 6 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.5 and 0.9 mM Li, respectively. Under these experimental conditions, no clinical side-effects were observed. Urea and creatinine concentrations in serum, lipids peroxidation level and activities of catalase, superoxide-dismutase and glutathione-peroxidase in liver and kidney were not significantly different from control values. Although the expression level of the constitutive HSP73 was not significantly modified, HSP72 was found to be down-regulated in kidney after 1 month. In liver, three protein bands were immunodetected by the anti-GRP94 antibody: 98 kDa and 96 kDa proteins corresponding to more or less glycosylated forms and/or phosphorylated forms of GRP94 and a 80 kDa protein probably being a cleavage product of GRP94. The 96 kDa and 80 kDa proteins were significantly up-regulated in liver of lithium-treated mice as compared to controls. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production.

    Science.gov (United States)

    Barton, Elisabeth R; Park, SooHyun; James, Jose K; Makarewich, Catherine A; Philippou, Anastassios; Eletto, Davide; Lei, Hanqin; Brisson, Becky; Ostrovsky, Olga; Li, Zihai; Argon, Yair

    2012-09-01

    Insulin-like growth factors (IGFs) are critical for development and growth of skeletal muscles, but because several tissues produce IGFs, it is not clear which source is necessary or sufficient for muscle growth. Because it is critical for production of both IGF-I and IGF-II, we ablated glucose-regulated protein 94 (GRP94) in murine striated muscle to test the necessity of local IGFs for normal muscle growth. These mice exhibited smaller skeletal muscles with diminished IGF contents but with normal contractile function and no apparent endoplasmic reticulum stress response. This result shows that muscles rely on GRP94 primarily to support local production of IGFs, a pool that is necessary for normal muscle growth. In addition, body weights were ∼30% smaller than those of littermate controls, and circulating IGF-I also decreased significantly, yet glucose homeostasis was maintained with little disruption to the growth hormone pathway. The growth defect was complemented on administration of recombinant IGF-I. Thus, unlike liver production of IGF-I, muscle IGF-I is necessary not only locally but also globally for whole-body growth.

  7. GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Marzec, Michal; Eletto, Davide; Argon, Yair

    2012-01-01

    Glucose-regulated protein 94 is the HSP90-like protein in the lumen of the endoplasmic reticulum and therefore it chaperones secreted and membrane proteins. It has essential functions in development and physiology of multicellular organisms, at least in part because of this unique clientele. GRP94...... shares many biochemical features with other HSP90 proteins, in particular its domain structure and ATPase activity, but also displays distinct activities, such as calcium binding, necessitated by the conditions in the endoplasmic reticulum. GRP94's mode of action varies from the general HSP90 theme...

  8. The endoplasmic reticulum chaperone protein GRP94 is required for maintaining hematopoietic stem cell interactions with the adult bone marrow niche.

    Directory of Open Access Journals (Sweden)

    Biquan Luo

    Full Text Available Hematopoietic stem cell (HSC homeostasis in the adult bone marrow (BM is regulated by both intrinsic gene expression products and interactions with extrinsic factors in the HSC niche. GRP94, an endoplasmic reticulum chaperone, has been reported to be essential for the expression of specific integrins and to selectively regulate early T and B lymphopoiesis. In GRP94 deficient BM chimeras, multipotent hematopoietic progenitors persisted and even increased, however, the mechanism is not well understood. Here we employed a conditional knockout (KO strategy to acutely eliminate GRP94 in the hematopoietic system. We observed an increase in HSCs and granulocyte-monocyte progenitors in the Grp94 KO BM, correlating with an increased number of colony forming units. Cell cycle analysis revealed that a loss of quiescence and an increase in proliferation led to an increase in Grp94 KO HSCs. This expansion of the HSC pool can be attributed to the impaired interaction of HSCs with the niche, evidenced by enhanced HSC mobilization and severely compromised homing and lodging ability of primitive hematopoietic cells. Transplanting wild-type (WT hematopoietic cells into a GRP94 null microenvironment yielded a normal hematology profile and comparable numbers of HSCs as compared to WT control, suggesting that GRP94 in HSCs, but not niche cells, is required for maintaining HSC homeostasis. Investigating this, we further determined that there was a near complete loss of integrin α4 expression on the cell surface of Grp94 KO HSCs, which showed impaired binding with fibronectin, an extracellular matrix molecule known to play a role in mediating HSC-niche interactions. Furthermore, the Grp94 KO mice displayed altered myeloid and lymphoid differentiation. Collectively, our studies establish GRP94 as a novel cell intrinsic factor required to maintain the interaction of HSCs with their niche, and thus regulate their physiology.

  9. Upregulation of Phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in Acquired Middle Ear Cholesteatoma Growth

    Directory of Open Access Journals (Sweden)

    Kuen Yao Ho

    2013-07-01

    Full Text Available Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.

  10. RNAi silenced Dd-grp94 (Dictyostelium discoideum glucose-regulated protein 94 kDa) cell lines in Dictyostelium exhibit marked reduction in growth rate and delay in development.

    Science.gov (United States)

    Baviskar, Sandhya N; Shields, Malcolm S

    2010-01-01

    Glucose-regulated 94 kDa protein (Grp94) is a resident of the endoplasmic reticulum (ER) of multicellular eukaryotes. It is a constitutively expressed protein that is overexpressed in certain abnormal conditions of the cell such as depletion of glucose and calcium, and low oxygen and pH. The protein is also implicated in diseased conditions like cancer and Alzheimer's disease. In this study, the consequences of downregulation of Grp94 were investigated at both unicellular and multicellular stages of Dictyostelium discoideum. Previous studies have shown the expression of Dd-Grp94 (Dictyostelium discoideum glucose-regulated 94 kDa protein) in wild-type cells varies during development, and overexpression of Dd-Grp94 leads to abnormal cell shape and inhibition of development (i.e., formation of fruiting bodies). Grp94 is a known calcium binding protein and an efficient calcium buffer. Therefore, in the present study we hypothesized that downregulation of Dd-Grp94 protein would affect Dictyostelium cell structure, growth, and development. We found that Dd-grp94 RNAi recombinants exhibited reduced growth rate, cell size, and a subtle change in cell motility compared to the parental cells. The recombinants also exhibited a delay in development and small fruiting bodies. These results establish that Dd-grp94 plays a crucial role in determining normal cell structure, growth and differentiation.

  11. A Human Variant of Glucose-Regulated Protein 94 That Inefficiently Supports IGF Production

    DEFF Research Database (Denmark)

    Marzec, Michal; Hawkes, Colin P; Eletto, Davide

    2016-01-01

    IGFs are critical for normal intrauterine and childhood growth and sustaining health throughout life. We showed previously that the production of IGF-1 and IGF-2 requires interaction with the chaperone glucose-regulated protein 94 (GRP94) and that the amount of secreted IGFs is proportional...... to the GRP94 activity. Therefore, we tested the hypothesis that functional polymorphisms of human GRP94 affect IGF production and thereby human health. We describe a hypomorphic variant of human GRP94, P300L, whose heterozygous carriers have 9% lower circulating IGF-1 concentration. P300L was found first...... in a child with primary IGF deficiency and was later shown to be a noncommon single-nucleotide polymorphism with frequencies of 1%-4% in various populations. When tested in the grp94(-/-) cell-based complementation assay, P300L supported only approximately 58% of IGF secretion relative to wild-type GRP94...

  12. Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94) expression in kidney and liver of rats under lithium treatment.

    Science.gov (United States)

    Nciri, Riadh; Allagui, Mohamed Salah; Bourogaa, Ezzedine; Saoudi, Monji; Murat, Jean-Claude; Croute, Françoise; Elfeki, Abdelfettah

    2012-03-01

    The present work was aimed at studying the effects of a subchronic lithium treatment on rat liver and kidneys, paying attention to the relationship between lithium toxicity, oxidative stress, and stress protein expression. Male rats were submitted to lithium treatment by adding 2 g of lithium carbonate/kg of food for different durations up to 1 month. This treatment led to serum concentrations ranging from 0.5 mM (day 7) to 1.34 mM (day 28) and renal insufficiency highlighted by an increase of blood creatinine and urea levels and a decrease of urea excretion. Lithium treatment was found to trigger an oxidative stress both in kidney and liver, leading to an increase of lipid peroxidation level (TBARS) and of superoxide dismutase and catalase activities. Conversely, glutathione peroxidase activity was reduced. Constitutive HSP73 (heat shock protein 73) expression was not modified by lithium treatment, whereas inducible HSP72 was down-regulated in kidney. GRP94 (glucose regulated protein 94) appeared as two isoforms of 92 and 98 kDa: the 98-kDa protein being overexpressed in kidney by lithium treatment whereas 92-kDa protein was underexpressed both in kidney and liver.

  13. Human Milk Glycoproteins Protect Infants Against Human Pathogens

    Science.gov (United States)

    Liu, Bo

    2013-01-01

    Abstract Breastfeeding protects the neonate against pathogen infection. Major mechanisms of protection include human milk glycoconjugates functioning as soluble receptor mimetics that inhibit pathogen binding to the mucosal cell surface, prebiotic stimulation of gut colonization by favorable microbiota, immunomodulation, and as a substrate for bacterial fermentation products in the gut. Human milk proteins are predominantly glycosylated, and some biological functions of these human milk glycoproteins (HMGPs) have been reported. HMGPs range in size from 14 kDa to 2,000 kDa and include mucins, secretory immunoglobulin A, bile salt-stimulated lipase, lactoferrin, butyrophilin, lactadherin, leptin, and adiponectin. This review summarizes known biological roles of HMGPs that may contribute to the ability of human milk to protect neonates from disease. PMID:23697737

  14. Are pharmaceutical patents protected by human rights?

    Science.gov (United States)

    Millum, J

    2008-11-01

    The International Bill of Rights enshrines a right to health, which includes a right to access essential medicines. This right frequently appears to conflict with the intellectual property regime that governs pharmaceutical patents. However, there is also a human right that protects creative works, including scientific productions. Does this right support intellectual property protections, even when they may negatively affect health? This article examines the recent attempt by the Committee on Economic, Social and Cultural Rights to resolve this issue and argues that it fails. This is problematic because it means defenders of the present patent regime can continue using human rights documents to support their position. I offer a new framework for resolving the problem by examining the values that underlie human rights.

  15. Human subjects research handbook: Protecting human research subjects. Second edition

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  16. Human embryonic stem cells and patent protection

    Directory of Open Access Journals (Sweden)

    Radovanović Sanja M.

    2015-01-01

    Full Text Available Given the importance of biotechnological research in modern diagnostics and therapeutics, on the one hand, and stimulative function of a patent, on the other hand, this work deals with the question of the possibility of pa-tent protection of human embryonic stem cells. Taking into account that this is a biotechnological invention, the key question that this paper highlights is the interpretation of the provisions of their patentability. Namely, thanks to the advanced methods of isolation, purification and preparation for implementation, modern patent systems do not exclude a priori living organisms from patent protection. Therefore, the analysis of representative administrative decisions or court rulings sought to define the criteria that would be applied in order to give patent protection to a certain biotechnological invention (stem cells while others do not.

  17. Criminal and Legal Aspects of Human Life Protection

    OpenAIRE

    Petra Janule

    2012-01-01

    The promotion work "Criminal and Legal Aspects of Human Life Protection" is the first such volume complex theoretical and practical research in Latvia on the legal protection of human life. The main idea of the thesis is the human right for physical existence and human life protection by the Criminal Law. The central idea of the thesis is the human rights to the physical existence from the moment of conception and the life protection with criminally legal instruments, which, fi...

  18. Institutional Mechanisms for Human Rights Protection in Nigeria: An ...

    African Journals Online (AJOL)

    . There are legal and institutional mechanisms for protecting the human rights guaranteed in these constitutions. This paper has focused on the institutional mechanisms for human rights protection in Nigeria. The meaning, features and ...

  19. Human physiology as the determining factor in protective clothing design

    NARCIS (Netherlands)

    Daanen, Hein

    2014-01-01

    Protective clothing is designed to protect humans against risks like fire, chemicals or blunt impact. Although protect¡ve clothing diminishes the effects of external risks, it may hinder people in functioning and it may also introduce new (internal) risks. Manufacturers are often not aware of the

  20. Mechanisms of protection against rotavirus in humans and mice.

    Science.gov (United States)

    Ward, R L

    1996-09-01

    Immune responses following either natural or experimental rotavirus infection provide protection against subsequent rotavirus illnesses, and the mechanisms involved have been examined in humans and animals. In adult volunteers challenged with human rotaviruses, protection has been shown to correlate with serum and intestinal antibodies; however, titers of no specific antibody could be used reliably as a marker of protection, including neutralizing antibody to the challenge virus. Studies in children confirmed these general associations between antibody titers and protection, but the serotype specificity of antibody and its role in protection remained unclear. Studies in mice suggested antibody, CD8 cells, and a third, undetermined, factor as mediators of protection. Antibody appeared to be most important, both in resolution of infection and protection against subsequent infection, but its activity was not serotype specific. CD8 cells helped resolve rotavirus infection but were less important in protection against reinfection. The third factor remains to be identified.

  1. Glycoconjugates in human milk: protecting infants from disease.

    Science.gov (United States)

    Peterson, Robyn; Cheah, Wai Yuen; Grinyer, Jasmine; Packer, Nicolle

    2013-12-01

    Breastfeeding is known to have many health benefits for a newborn. Not only does human milk provide an excellent source of nutrition, it also contains components that protect against infection from a wide range of pathogens. Some of the protective properties of human milk can be attributed to the immunoglobulins. Yet, there is another level of defense provided by the "sweet" protective agents that human milk contains, including free oligosaccharides, glycoproteins and glycolipids. Sugar epitopes in human milk are similar to the glycan receptors that serve as pathogen adhesion sites in the human gastrointestinal tract and other epithelial cell surfaces; hence, the milk glycans can competitively bind to and remove the disease-causing microorganisms before they cause infection. The protective value of free oligosaccharides in human milk has been well researched and documented. Human milk glycoconjugates have received less attention but appear to play an equally important role. Here, we bring together the breadth of research that has focused on the protective mechanisms of human milk glycoconjugates, with a particular focus on the glycan moieties that may play a role in disease prevention. In addition, human milk glycoconjugates are compared with bovine milk glycoconjugates in terms of their health benefits for the human infant.

  2. Child protection from trafficking in humans

    OpenAIRE

    Žegarac Nevenka

    2005-01-01

    Trafficking in children is particularly severe form of exploitation and breach of the children rights, while security and welfare of children that are exposed to trafficking are obligations of state authorities, services and organizations of civil society. System of protection and support to children victims of trafficking should contain following: criteria for proper identification of child-victim of trafficking, mechanisms for immediate referring of a child to specialized services, procedur...

  3. Child protection from trafficking in humans

    Directory of Open Access Journals (Sweden)

    Žegarac Nevenka

    2005-01-01

    Full Text Available Trafficking in children is particularly severe form of exploitation and breach of the children rights, while security and welfare of children that are exposed to trafficking are obligations of state authorities, services and organizations of civil society. System of protection and support to children victims of trafficking should contain following: criteria for proper identification of child-victim of trafficking, mechanisms for immediate referring of a child to specialized services, procedures for appointing a guardian who will secure that procedures and decisions are in accordance with the best interest of child, measures for regulating of residential status, assistance with reparation and reintegration as well as measures for protection of children witnesses and victims of trafficking. Finally, it should include a proper access to justice. In the article, recommendations are proposed for improvement of identification system, proper evaluation of needs and planning services and protection measures as well as measures and activities which should secure long term solutions in accordance with rights of the child and her/his best interests.

  4. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    , and the probable mechanism. Methods: After ... Keywords: Mitochondrial transcription factor A, NF-κB, Hypoxia, Human retinal endothelial cell,. Diabetic retinopathy ..... choice for diabetic retinopathy therapy, as TFAM activity clearly affects the ...

  5. Human rights protection under the FDRE and the Oromia ...

    African Journals Online (AJOL)

    This paper makes a comparative analysis of human rights protection as provided under the 1995 Federal Democratic Republic of Ethiopian Constitution (FDRE Constitution) and the 2001 Oromia Regional State Revised Constitution with its amendments (OromiaConstitution). Guided by the principle of a better protection of ...

  6. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  7. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were ...

  8. Progress in the international protection of human rights.

    Science.gov (United States)

    Suter, Keith

    2002-01-01

    Great progress has been made in the international protection of human rights since 10 December 1948 (when the United Nations General Assembly adopted the Universal Declaration of Human Rights). Amidst the doom and gloom of the media's reporting of current affairs, it is easy to overlook this progress. This article provides a definition of 'human rights' and examines early human rights campaigns. It then considers the areas of progress: human rights are now part of the international political vocabulary, there is a recognition that respect for human rights can assist a country's economic and social development, there has been a growth of human rights treaties and techniques and non-governmental organizations (NGOs) see protecting human rights as a major activity. State sovereignty has been eroded as national governments are being held accountable to the international community for their human rights policies. A new challenge is to ensure respect for human rights by non-state entities, such as transnational corporations. The growing culture of international protection of human rights is here to stay. This is not a reason for complacency, but it is a sign of hope.

  9. institutional mechanisms for human rights protection in nigeria

    African Journals Online (AJOL)

    Mofasony

    legal and institutional mechanisms for protecting the human rights guaranteed in these constitutions. ... U.O. Umuzurike Introduction to international Law, Spectrum Law Publishing, Ibadan, 1995 p.141. 2. G Ezejiofor. ... Liaise and cooperate with local and international organizations on human rights for the purpose of ...

  10. Reimagining Human Research Protections for 21st Century Science.

    Science.gov (United States)

    Bloss, Cinnamon; Nebeker, Camille; Bietz, Matthew; Bae, Deborah; Bigby, Barbara; Devereaux, Mary; Fowler, James; Waldo, Ann; Weibel, Nadir; Patrick, Kevin; Klemmer, Scott; Melichar, Lori

    2016-12-22

    Evolving research practices and new forms of research enabled by technological advances require a redesigned research oversight system that respects and protects human research participants. Our objective was to generate creative ideas for redesigning our current human research oversight system. A total of 11 researchers and institutional review board (IRB) professionals participated in a January 2015 design thinking workshop to develop ideas for redesigning the IRB system. Ideas in 5 major domains were generated. The areas of focus were (1) improving the consent form and process, (2) empowering researchers to protect their participants, (3) creating a system to learn from mistakes, (4) improving IRB efficiency, and (5) facilitating review of research that leverages technological advances. We describe the impetus for and results of a design thinking workshop to reimagine a human research protections system that is responsive to 21st century science.

  11. Planetary protection for humans in space: Mars and the Moon

    Science.gov (United States)

    Conley, Catharine A.; Rummel, John D.

    When searching for life beyond Earth, the unique capabilities provided by human astronauts will only be advantageous if the biological contamination associated with human presence is monitored and minimized. Controlling biological contamination during planetary exploration is termed 'planetary protection,' and will be a critical element in the human exploration of other solar system bodies. To ensure the safety and health of the astronauts and the Earth, while preserving science value, planetary protection considerations must be incorporated from the earliest stages of mission planning and development. Issues of concern to planetary protection involve both 'forward contamination,' which is the contamination of other solar system bodies by Earth microbes and organic materials, and 'backward contamination,' which is the contamination of Earth systems by potential alien life. Forward contamination concerns include contamination that might invalidate current or future scientific exploration of a particular solar system body, and that may disrupt the planetary environment or a potential endogenous (alien) ecosystem. Backward contamination concerns include both immediate and long-term effects on the health of the astronaut explorers from possible biologically active materials encountered during exploration, as well as the possible contamination of the Earth. A number of national and international workshops held over the last seven years have generated a consensus regarding planetary protection policies and requirements for human missions to Mars, and a 2007 workshop held by NASA has considered the issues and benefits to planetary protection that might be offered by a return to the Moon. Conclusions from these workshops recognize that some degree of forward contamination associated with human astronaut explorers is inevitable. Nonetheless, the principles and policies of planetary protection, developed by COSPAR in conformance with the 1967 Outer Space Treaty, can and

  12. Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions: Workshop Report

    Science.gov (United States)

    Race, Margaret S. (Editor); Johnson, James E. (Editor); Spry, James A. (Editor); Siegel, Bette; Conley, Catharine A.

    2015-01-01

    This report on Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions summarizes the presentations, deliberations and findings of a workshop at NASA Ames Research Center, March 24-26, 2015, which was attended by more than 100 participants representing a diverse mix of science, engineering, technology, and policy areas. The main objective of the three-day workshop was to identify specific knowledge gaps that need to be addressed to make incremental progress towards the development of NASA Procedural Requirements (NPRs) for Planetary Protection during human missions to Mars.

  13. Protection of human rights in South Africa: public awareness and ...

    African Journals Online (AJOL)

    To that end, the survey sought information on public knowledge or awareness of the Bill of Rights, violation or protection of various types of rights, and awareness and perceptions regarding human rights institutions. It was found that many South Africans are unaware of the existence of the Bill of Rights and that the majority ...

  14. The protection of individuals by means of diplomatic protection : diplomatic protection as a human rights instrument

    NARCIS (Netherlands)

    Vermeer-Künzli, Anna Maria Helena

    2007-01-01

    Individuals whose international (human) rights are violated outside their state of nationality often have very limited means to address such violations. For instance, the foreign nationals detained by the United States in Guantanamo Bay have been unable to improve their situation themselves. Their

  15. The interaction of human population, food production, and biodiversity protection.

    Science.gov (United States)

    Crist, Eileen; Mora, Camilo; Engelman, Robert

    2017-04-21

    Research suggests that the scale of human population and the current pace of its growth contribute substantially to the loss of biological diversity. Although technological change and unequal consumption inextricably mingle with demographic impacts on the environment, the needs of all human beings-especially for food-imply that projected population growth will undermine protection of the natural world. Numerous solutions have been proposed to boost food production while protecting biodiversity, but alone these proposals are unlikely to staunch biodiversity loss. An important approach to sustaining biodiversity and human well-being is through actions that can slow and eventually reverse population growth: investing in universal access to reproductive health services and contraceptive technologies, advancing women's education, and achieving gender equality. Copyright © 2017, American Association for the Advancement of Science.

  16. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  17. The Effect of Protected Wilderness Spaces on Local Human Population

    OpenAIRE

    Griffin, Drew; Duda, Kaylyn; Brosch, Geoff

    2014-01-01

    The goal of this project is to analyze the effect that protected wilderness areas have on local human populations through the use of GIS. Using data from Northern Tanzania and from Virginia we hope to discover the degree and kind of difference between these two very different areas. Our current theory based on accounts by people who have traveled in the respective regions is that in Tanzania the protected areas have forced people to move and change their habits and home places whereas in Virg...

  18. Using human data to protect the public's health.

    Science.gov (United States)

    Dourson, M L; Andersen, M E; Erdreich, L S; MacGregor, J A

    2001-04-01

    The value of using human data in the assessment and management of risk is evaluated. Although the use of such data has a long and successful history with environmental contaminants and the development of drugs and commercial chemicals, recent deliberations within the Environmental Protection Agency (EPA) have questioned this practice in part. Specifically, we evaluate the degree to which reference doses (RfDs) and reference concentrations (RfCs) derived from human data on EPA's Integrated Risk Information System (IRIS) differ with RfDs and RfCs that we estimate from experimental animal data. We also use several minimal risk levels of the Agency for Toxic Substances and Disease Registry (ATSDR) and tolerable intakes of Health Canada in this comparison. Human-based RfDs are more than threefold lower than the corresponding animal-based RfDs for 23% of the comparisons. Human- based RfDs or RfCs are lower than corresponding animal-based RfDs or RfCs for 36% of the comparisons. Furthermore, for 10 of 43 possible comparisons, insufficient experimental animal data are readily available or data are inappropriate to estimate either RfDs or RfCs. We also discuss human pharmacokinetic data from volunteer studies and mechanistic studies with human tissues in vitro and demonstrate through a series of case discussions that utilization of such data is important when making decisions to protect exposed individuals. Moreover, physiologically based pharmacokinetic (PBPK) modeling evaluates critical information in assessing interindividual variability and identifying at-risk populations. Within the limits of our analysis, we conclude that the direct use and interpretation of human data, in conjunction with data gathered from experimental animals, are public health protective policies that should be encouraged. Copyright 2001 Academic Press.

  19. Effectiveness of Human Research Protection Program Performance Measurements.

    Science.gov (United States)

    Tsan, Min-Fu; Nguyen, Yen

    2017-10-01

    We analyzed human research protection program performance metric data of all Department of Veterans Affairs research facilities obtained from 2010 to 2016. Among a total of 25 performance metrics, 21 (84%) showed improvement, four (16%) remained unchanged, and none deteriorated during the study period. The overall improvement from these 21 performance metrics was 81.1% ± 18.7% (mean ± SD), with a range of 30% to 100%. The four performance metrics that did not show improvement all had initial noncompliance/incidence rates of performance metrics that showed improvement ranged from 0.05% to 60%. However, of the 21 performance metrics that showed improvement, 10 had initial noncompliance/incidence rates of performance measurement is an effective tool in improving the performance of human research protection programs.

  20. Human migration, protected areas, and conservation outreach in Tanzania

    OpenAIRE

    Salerno, JD; Mulder, MB; Kefauver, SC

    2014-01-01

    A recent discussion debates the extent of human in-migration around protected areas (PAs) in the tropics. One proposed argument is that rural migrants move to bordering areas to access conservation outreach benefits. A counter proposal maintains that PAs have largely negative effects on local populations and that outreach initiatives even if successful present insufficient benefits to drive in-migration. Using data from Tanzania, we examined merits of statistical tests and spatial methods use...

  1. Basic Science Research and the Protection of Human Research Participants

    Science.gov (United States)

    Eiseman, Elisa

    2001-03-01

    Technological advances in basic biological research have been instrumental in recent biomedical discoveries, such as in the understanding and treatment of cancer, HIV/AIDS, and heart disease. However, many of these advances also raise several new ethical challenges. For example, genetic research may pose no physical risk beyond that of obtaining the initial blood sample, yet it can pose significant psychological and economic risks to research participants, such as stigmatization, discrimination in insurance and employment, invasion of privacy, or breach of confidentiality. These harms may occur even when investigators do not directly interact with the person whose DNA they are studying. Moreover, this type of basic research also raises broader questions, such as what is the definition of a human subject, and what kinds of expertise do Institutional Review Boards (IRBs) need to review the increasingly diverse types of research made possible by these advances in technology. The National Bioethics Advisory Commission (NBAC), a presidentially appointed federal advisory committee, has addressed these and other ethical, scientific and policy issues that arise in basic science research involving human participants. Two of its six reports, in particular, have proposed recommendations in this regard. "Research Involving Human Biological Materials: Ethical and Policy Guidance" addresses the basic research use of human tissues, cells and DNA and the protection of human participants in this type of research. In "Ethical and Policy Issues in the Oversight of Human Research" NBAC proposes a definition of research involving human participants that would apply to all scientific disciplines, including physical, biological, and social sciences, as well as the humanities and related professions, such as business and law. Both of these reports make it clear that the protection of research participants is key to conducting ethically sound research. By ensuring that all participants in

  2. The Human Rights and the Social Protection of Vulnerable Individuals

    Directory of Open Access Journals (Sweden)

    Cătălina Mititelu

    2012-08-01

    Full Text Available In the texts with binding juridical force, drafted and published by the Council of theEuropean Union, we find no provisions regarding the juridical protection of the vulnerable persons (disabled persons, old people and mentally retarded, only planned measures regarding their social protection, that the E.U. States granted in the Social Charter (of 1961 and in the revised one of 1996, and, finally, in the additional Protocol from the year 1988. Given that to know these measures – that also remain compulsory for the signatory States or for the ones that ratified this Charter – is not possible without getting acquainted, at least in brief, with the human Rights provided by the E.U. legislation, within the pages of this study we referred explicitly to the text of the latter in order to evince the imperious necessity to draft a special legislation also regarding the juridical protection of vulnerable persons, not only a protection of a preeminently social nature.

  3. Protective Effects of Triphala on Dermal Fibroblasts and Human Keratinocytes.

    Directory of Open Access Journals (Sweden)

    Sandeep R Varma

    Full Text Available Human skin is body's vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF and human keratinocytes (HaCaT were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2 induced RBC haemolysis (IC50 64.95 μg/mL, nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2, aquaporin-3 (AQP-3, filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations.

  4. Planetary health: protecting human health on a rapidly changing planet.

    Science.gov (United States)

    Myers, Samuel S

    2018-12-23

    The impact of human activities on our planet's natural systems has been intensifying rapidly in the past several decades, leading to disruption and transformation of most natural systems. These disruptions in the atmosphere, oceans, and across the terrestrial land surface are not only driving species to extinction, they pose serious threats to human health and wellbeing. Characterising and addressing these threats requires a paradigm shift. In a lecture delivered to the Academy of Medical Sciences on Nov 13, 2017, I describe the scale of human impacts on natural systems and the extensive associated health effects across nearly every dimension of human health. I highlight several overarching themes that emerge from planetary health and suggest advances in the way we train, reward, promote, and fund the generation of health scientists who will be tasked with breaking out of their disciplinary silos to address this urgent constellation of health threats. I propose that protecting the health of future generations requires taking better care of Earth's natural systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  6. Human subjects protection issues in QUERI implementation research: QUERI Series

    Directory of Open Access Journals (Sweden)

    Ritchie Mona

    2008-02-01

    Full Text Available Abstract Background Human Subjects protections approaches, specifically those relating to research review board oversight, vary throughout the world. While all are designed to protect participants involved in research, the structure and specifics of these institutional review boards (IRBs can and do differ. This variation affects all types of research, particularly implementation research. Methods In 2001, we began a series of inter-related studies on implementing evidence-based collaborative care for depression in Veterans Health Administration primary care. We have submitted more than 100 IRB applications, amendments, and renewals, and in doing so, we have interacted with 13 VA and University IRBs across the United States (U.S.. We present four overarching IRB-related themes encountered throughout the implementation of our projects, and within each theme, identify key challenges and suggest approaches that have proved useful. Where applicable, we showcase process aids developed to assist in resolving a particular IRB challenge. Results There are issues unique to implementation research, as this type of research may not fit within the traditional Human Subjects paradigm used to assess clinical trials. Risks in implementation research are generally related to breaches of confidentiality, rather than health risks associated with traditional clinical trials. The implementation-specific challenges discussed are: external validity considerations, Plan-Do-Study-Act cycles, risk-benefit issues, the multiple roles of researchers and subjects, and system-level unit of analysis. Discussion Specific aspects of implementation research interact with variations in knowledge, procedures, and regulatory interpretations across IRBs to affect the implementation and study of best methods to increase evidence-based practice. Through lack of unambiguous guidelines and local liability concerns, IRBs are often at risk of applying both variable and inappropriate or

  7. 48 CFR 1352.235-71 - Protection of human subjects-exemption.

    Science.gov (United States)

    2010-10-01

    ...; (2) Documentation of approval for the human subjects research protocol, questionnaires, surveys..., if the contractor modifies a human subjects research protocol, questionnaire, survey, advertisement... forth in solicitation #____, related to the Protection of Human Subjects in research. The Government has...

  8. Does biodiversity protect humans against infectious disease? Reply

    Science.gov (United States)

    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  9. 10 CFR 63.321 - Individual protection standard for human intrusion.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Individual protection standard for human intrusion. 63.321... Standards Human Intrusion Standard § 63.321 Individual protection standard for human intrusion. (a) DOE must... intrusion (see § 63.322) could occur without recognition by the drillers. (b) DOE must demonstrate that...

  10. Immunoregulation in Human American Leishmaniasis: Balancing Pathology and Protection

    Science.gov (United States)

    Gollob, Kenneth J.; Viana, Agostinho G.; Dutra, Walderez O.

    2014-01-01

    Summary Leishmaniasis covers a broad spectrum of diseases with distinct, and sometimes overlapping, characteristics. The common thread in all forms of leishmaniasis is the infection by the parasite Leishmania belonging to the genus Leishmania. Upon infection of humans there can be at least three outcomes, 1) control of Leishmania by the host immune response resulting in asymptomatic disease, 2) patent infection and development of a relatively mild form of leishmaniasis, and 3) patent infection and development of severe clinical forms. The factors that determine the outcome of an initial inoculation with Leishmania are many, with the species of Leishmania representing one of the strongest predictive factors for the development of a given clinical form of disease. This is seen with L. braziliensis and L. amazonensis, infection leading mostly to tegumentary forms of disease, and L. infantum with the potential to induce visceral disease. However, it is also clear that the host immune response is a key factor in disease progression, not only responsible for control of Leishmania, but also playing an important role in disease progression and pathology. This duality between protective and pathogenic immune responses in individuals infected with Leishmania in the Americas is the focus of this review. PMID:24471648

  11. Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis.

    Science.gov (United States)

    Wang, Ying; Chen, Baosheng; Longtine, Mark S; Nelson, D Michael

    2016-02-01

    Punicalagin is a prominent polyphenol in pomegranate juice that protects cultured syncytiotrophoblasts from stress-induced apoptosis. Here, we test the hypothesis that punicalagin has this effect by inhibiting the mTOR kinase pathway to enhance autophagic turnover and limit apoptosis in cultured primary human syncytiotrophoblasts. In syncytiotrophoblasts, starvation, rapamycin, or punicalagin all decreased the expression of phosphorylated ribosomal protein S6, a downstream target of the mTOR kinase, and of the autophagy markers, LC3-II and p62. In contrast, in the presence of bafilomycin, an inhibitor of late stages of autophagy and degradation in the autophagolysosome, syncytiotrophoblasts exposed to starvation, rapamycin, or punicalagin all showed increased levels of LC3-II and p62. The number of LC3-II punctae also increased in punicalagin-treated syncytiotrophoblasts exposed to chloroquine, another inhibitor of autophagic degradation, and punicalagin increased the number of lysosomes. The apoptosis-reducing effect of punicalagin was attenuated by inhibition of autophagy using bafilomycin or knockdown of the autophagy related gene, ATG16L1. Collectively, these data support the hypothesis that punicalagin modulates the crosstalk between autophagy and apoptosis to promote survival in cultured syncytiotrophoblasts. © 2016 Society for Reproduction and Fertility.

  12. Human migration, protected areas, and conservation outreach in Tanzania.

    Science.gov (United States)

    Salerno, Jonathan D; Borgerhoff Mulder, Monique; Kefauver, Shawn C

    2014-06-01

    A recent discussion debates the extent of human in-migration around protected areas (PAs) in the tropics. One proposed argument is that rural migrants move to bordering areas to access conservation outreach benefits. A counter proposal maintains that PAs have largely negative effects on local populations and that outreach initiatives even if successful present insufficient benefits to drive in-migration. Using data from Tanzania, we examined merits of statistical tests and spatial methods used previously to evaluate migration near PAs and applied hierarchical modeling with appropriate controls for demographic and geographic factors to advance the debate. Areas bordering national parks in Tanzania did not have elevated rates of in-migration. Low baseline population density and high vegetation productivity with low interannual variation rather than conservation outreach explained observed migration patterns. More generally we argue that to produce results of conservation policy significance, analyses must be conducted at appropriate scales, and we caution against use of demographic data without appropriate controls when drawing conclusions about migration dynamics. © 2014 Society for Conservation Biology.

  13. The Functions of Selected Human Rights Institutions and Related Role-Players in the Protection of Human Rights in Zimbabwe

    Directory of Open Access Journals (Sweden)

    Howard Chitimira

    2016-12-01

    Full Text Available Various violations of the human rights of ordinary people and human rights defenders have been reported in Zimbabwe since the late 1980s. It is widely acknowledged that such violations have been perpetrated mostly by the government through its different organs for political and other related reasons. Human rights violations were also easily committed against ordinary people and human rights defenders because there was no Constitution that adequately protected such people's fundamental human rights (including their civil and political rights and their socio-economic rights in Zimbabwe. Given this background, the article discusses the protection of human rights in Zimbabwe, in the light of the Zimbabwe Constitution Amendment Act 20 of 2013 (Zimbabwe Constitution 2013. This is done in order to investigate whether the promotion, protection, enforcement and respect for human rights in Zimbabwe has now improved. To this end, the functions of selected national human rights institutions and other related role-players, namely civil society, the judiciary, the law enforcement organs and the Zimbabwe Human Rights Commission, are briefly discussed first. Secondly, the functions of selected regional and international institutions, namely the Southern African Development Community, the African Union and the United Nations are discussed in relation to the protection of human rights in Zimbabwe. Thereafter, concluding remarks and possible recommendations that could be utilised to combat human rights violations and enhance the protection of human rights in Zimbabwe are provided.

  14. Strategies for Protecting and Implementing Human Rights in Today

    OpenAIRE

    Montesinos Oltra, Salvador; Añón Roig, María José

    2010-01-01

    Human Rights and integration: and appraisal from Europe. Conference on Human Rigths Research Centres and Institutes. December 2-3, 2010. Institut de Drets Humans. Universitat de València.Duración:49M

  15. Evolving International Practices for Protection of Human Rights- the UN Human Rights Advisory Panel and EU Human Rights Review Panel

    Directory of Open Access Journals (Sweden)

    Remzije ISTREFI

    2017-03-01

    Full Text Available This article analyses the unique development of the international human rights non judicial protection mechanism in Kosovo. Since 1999 Kosovo has been placed under international supervision carried out by international organizations, namely the United Nations and the European Union. The UN’s Mission in Kosovo (UNMK was unprecedented both in scope and structural complexity. After the Declaration of Independence by Kosovo authorities on 17 February 2008, the European Union Rule of Law Mission in Kosovo EULEX took over to assist and support the Kosovo authorities in the rule of law area, specifically in the areas of the police, the judiciary and customs. The UNMIK’s extensive mandate and EULEXs limited executive powers in practice have affected human rights of Kosovars as a consequence of the UNMIK and EULEX actions and inactions in the course of exercise of their mandates. This study will try to reveal the processes that lead to establishment of these two unique international human rights Panels and their impact on human rights protection of individuals under international administration. The main question to be addressed is if these two human rights panels are providing the adequate remedy for addressing human rights violations by international actors in a post conflict Kosovo.

  16. Declining human population but increasing residential development around protected areas in Puerto Rico

    Science.gov (United States)

    J. Castro-Prieto; S. Martinuzzi; V.C. Radeloff; D.P. Helmers; M. Quiñones; W.A. Gould

    2017-01-01

    Increasing residential development around protected areas is a major threat for protected areas worldwide, and human population growth is often the most important cause. However, population is decreasing in many regions as a result of socio-economic changes, and it is unclear how residential development around protected areas is affected in these situations. We...

  17. Evolving International Practices for Protection of Human Rights- the UN Human Rights Advisory Panel and EU Human Rights Review Panel

    OpenAIRE

    Istrefi, Remzije

    2017-01-01

    This article analyses the unique development of the international human rights non judicial protection mechanism in Kosovo. Since 1999 Kosovo has been placed under international supervision carried out by international organizations, namely the United Nations and the European Union. The UN’s Mission in Kosovo (UNMK) was unprecedented both in scope and structural complexity. After the Declaration of Independence by Kosovo authorities on 17 February 2008, the European Union Rule ...

  18. 48 CFR 1352.235-70 - Protection of human subjects.

    Science.gov (United States)

    2010-10-01

    ... subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms... . (f) In addition, if the contractor modifies a human subjects research protocol, questionnaire, survey... of Human Subjects (APR 2010) (a) Research involving human subjects is not permitted under this award...

  19. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

    2014-02-15

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

  20. Does protecting humans protect the environment? A crude examination for UK nuclear power plants and the marine environment using information in the public domain.

    Science.gov (United States)

    Brownless, G P

    2008-12-01

    Current activity around radiological protection of the environment implies concerns over the effectiveness of the current approach to this--namely if humans are adequately protected, then so are non-human species. This study uses models and data currently available in the public domain to carry out a 'quick and dirty' examination of whether protecting humans does indeed imply that other species are well protected. Using marine discharges and human habits data for operational coastal UK nuclear power stations, this study compares doses to humans and a set of reference non-human species. The study concludes that the availability of data and models, and consequent ease of studying potential effects on non-humans (as well as humans), vindicates recent efforts in this area, and that these imply a high level of protection, in general, for non-human biota from UK nuclear power station marine discharges. In general terms, the study finds that protection of non-human biota relies on taking ingestion and external exposure doses to humans into account; where only one of these pathways is considered, the level of protection of non-human biota through protection of humans would depend on the radionuclide(s) in question.

  1. Historic Preservation An unusual way to protect human subjects in research

    Energy Technology Data Exchange (ETDEWEB)

    Prendergast, Ellen L.

    2001-09-15

    The Hanford Cultural Resources Laboratory (HCRL) at the Hanford Site interacts with human subjects in a variety of ways, some of which constitute human subjects research. A key element in this work is determining what constitutes 'research' and thus requires application of special measures to protect human subjects.

  2. Protective Effect of Modified Human Acidic Fibroblast Growth Factor ...

    African Journals Online (AJOL)

    Purpose: To investigate whether modified acidic fibroblast growth factor (MaFGF) can protect NRK52E cell against apoptotic death induced by actinomycin D (Act D) and the effect of MaFGF on PI3K/Akt signaling pathway. Methods: NRK52E cell apoptotic death was measured by several methods including cell morphologic ...

  3. Managing Human Activities in Antarctica : Should Wilderness Protection Count?

    NARCIS (Netherlands)

    Bastmeijer, C.J.

    2005-01-01

    Antarctica is often described as one of the world's last wildernesses. In harmony with this general perception, the wilderness values of Antarctica received legal status with the adoption of the Protocol on Environmental Protection to the Antarctic Treaty. Article 3(1) of the Protocol obliges each

  4. Protective Effect of Modified Human Acidic Fibroblast Growth Factor ...

    African Journals Online (AJOL)

    HP

    and 1.0 mg/L) decreased apoptotic rate but enhanced the expression of phosphorylated Akt protein. However, MaFGF's protection ... PI3K/Akt signaling pathway by up-regulation of expression of phosphorylated Akt protein. Keywords: Modified acidic ... inhibitor, can inhibit protein synthesis. Recent studies have shown that ...

  5. Institutional Mechanisms for Human Rights Protection in Nigeria: An ...

    African Journals Online (AJOL)

    This paper concludes by making some recommendations that will strengthen these institutions in the discharge of their duties under enabling laws. It must be pointed out that the court is a major institution involved in the protection of the first generation rights. However, the role of the court will not be discussed in this article.

  6. LEGAL PROTECTION AGAINST CHILDREN WHO ARE VICTIMS OF HUMAN TRAFFICKING IN CIANJUR DISTRICT STUDIED BY HUMAN RIGHTS PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Henny Nuraeny

    2015-05-01

    Full Text Available Trafficking in persons is a modern form of slavery. The eradication of human trafficking has been on the agenda in law enforcement because of its effects can interfere with social welfare. One form of trafficking in persons who lately is rampant child trafficking. The problems that can be studied is how the perspective of Human Rights in providing protection to children who are victims of trafficking and whether the implementation of legal protection for child victims of trafficking in Cianjur is in line with the concept of human rights. This study uses normative juridical approach and specification of descriptive analysis. Results from this study is the protection of child victims of trafficking in persons has been referred to the concept of human rights which the regional government make policies on prevention of trafficking, rehabilitation, counseling and empowerment of victims of human trafficking.

  7. PENAL PROTECTION OF THE HUMAN EMBRYO. NEW CHALLENGES FOR ROMANIA

    OpenAIRE

    Laura STANILA

    2014-01-01

    The rapid developments in the last decades in the fields of biology and medicine raise important issues regarding the need to respect the human being both as an individual and in its membership in the human species. Medical acts performed both in research and in terms of curative work must be subordinated to a goal: the need to respect human dignity. In their desire to discover new treatments or just out of curiosity, biology and medicine can become instruments through an improper use, to end...

  8. Patents and the obligation to protect health: examining the significance of human rights considerations in the protection of pharmaceutical patents.

    Science.gov (United States)

    Owoeye, Olasupo Ayodeji

    2014-06-01

    This article discusses the human right to health in the context of patent protection and access to medicines. It considers the limitations in international human rights law, especially in relation to socioeconomic rights, that make it difficult for the right to health to be a potent justification for derogation from trade or intellectual property agreements. It concludes by taking the view that while the right to health may be somewhat unenforceable in international law, its close association with enforceable rights such as the right to life can be a legitimate basis for making maximum use of the flexibilities in the international intellectual property regime to protect public health. The article takes the view that trade and intellectual property agreements must be interpreted in a way that endeavours as much as possible to resolve any seeming inconsistency with the right to health.

  9. Acompañamiento in Colombia: international human rights protection of IDPs

    Directory of Open Access Journals (Sweden)

    Luis Enrique Eguren

    1999-04-01

    Full Text Available The deployment of international observerscan effectively deter human rights violationsagainst displaced people and those workingwith them. This article discusses the role oforganisations such as Peace BrigadesInternational in providing international humanrights protection.

  10. Multilayer Polymeric Shielding to Protect Humans from Galactic Cosmic Radiation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In Sub-topic X4.01, NASA has identified a need for advanced radiation-shielding materials and structures to protect humans from the hazards of galactic cosmic...

  11. Ibutilide protects against cardiomyocytes injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways.

    Science.gov (United States)

    Wang, Yu; Wang, Yi-Li; Huang, Xia; Yang, Yang; Zhao, Ya-Jun; Wei, Cheng-Xi; Zhao, Ming

    2017-02-01

    Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid atrial activation and atrial structural remodeling. The contribution of endoplasmic reticulum and mitochondria stress to AF has been highlighted. As the class III antiarrhythmic agent, ibutilide are widely used to AF. This study was designed to explore whether ibutilide could treat AF by inhibiting endoplasmic reticulum stress pathways and mitochondria stress. The neonatal rat cardiomyocytes were isolated and exposed to H2O2, ibutilide was add to the culture medium 12 h. Then the cell viability, oxidative stress levels and apoptotic rate were analyzed. In addition, endoplasmic reticulum stress related protein (GRP78, GRP94, CHOP), mitochondria-dependent protein (Bax, Bcl-2) and caspase-3/9/12 were identified by real-time PCR and western blot analysis. In our results, remarkable decreased cell viability and oxidative stress levels were detected in cardiomyocytes after treating with H2O2. The apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased. While ibutilide significantly inhibited these changes. These data suggested that ibutilide serves a protective role against H2O2-induced apoptosis of neonatal rat cardiomyocytes, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress.

  12. [Human cloning and the protection of women's interests].

    Science.gov (United States)

    Canabes, Marcela Ahumada

    2008-01-01

    The Human Cloning, both therapeutic and full birth cloning, involves and affects women in a special way. The United Nation's Declaration on the Cloning of Human Beings includes a special clause referred to them. Also the Spanish law does it. This works pretend to analyse the meaning of the inclusion of women's interests in this document. At the same time, I will consider the foundations and the importance of the reference to the women.

  13. Understanding the transformative aspects of the Wilderness and Protected Lands experience upon human health

    Science.gov (United States)

    Alan Ewert; Jillisa Overholt; Alison Voight; Chun Chieh Wang

    2011-01-01

    Wilderness and Protected Landscapes (WPLs) have long been considered special areas for a variety of reasons including baseline data, impact analyses, protected zones, and other tangible and intangible values. Another salient, and some would argue, a more important value offered through WPLs is that of human transformation. Accordingly, three theories have provided the...

  14. Protection of asylum seekers and illegal migrants human rights: Practice of the European Court of Human Rights

    Directory of Open Access Journals (Sweden)

    Đukanović Anđela

    2015-01-01

    Full Text Available Protection of asylum seeker and Illegal migrants human rights, has often been difficult due to the need of states to regulate unwanted migration flows. European Court of Human Rights plays an important role in protecting the rights of these individuals, through a set of human rights. Requests for interim measures under Rule 39 of the Rules of Court also have great importance. In cases involving illegal migrants and asylum-seekers, Court was often in difficult position, given the contradictions that could arise from the protection of human rights and the legitimate aim of the Contracting States to control the entry, residence and expulsion of aliens. Recent Courts judgment in case of M. S. S. against Belgium is particularly important, because of its remarkable influence on the perception of a common asylum system in the EU, as well as the judgment in the case of Jama Hirsi and Others v. Italy.

  15. Ecohealth Chair on Human and Animal Health in Protected ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Threats to African wildlife habitats As more and more people move in and around Africa's wildlife conservation areas, there is increased land degradation, biodiversity loss, and health risks for both humans and animals. In East and Central Africa, a number of factors are causing social and environmental change for ...

  16. Ecohealth Chair on Human and Animal Health in Protected ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    There are also significant knowledge gaps on potential long-term effects on human and animal health, ecosystem sustainability, and costs and benefits of potential mitigation strategies. Through the Ecohealth Chair position, this project will foster a body of evidence and knowledge, research capacity, and collaboration to ...

  17. Universal Protection of Human Rights: A Cross-Cultural Perspective ...

    African Journals Online (AJOL)

    Journal of Language, Technology & Entrepreneurship in Africa ... There is no denying the fact that the multiple processes of 'globalisation', which are taking place these days on a large scale, have caused significant transformations in almost all life aspects ... Key words: globalization, cross-cultural, human rights, universal ...

  18. 76 FR 44512 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-07-26

    ... organizations (CROs), data and safety monitoring committees, community-based organizations, and other entities... neuroscience has led to substantial advances in the understanding of human physiology, cognition, and behavior... subjects? What entity or organization should develop and disseminate such standardized document formats...

  19. The Protection of Human Rights in Saudi Counter-terrorism Laws

    Directory of Open Access Journals (Sweden)

    Faleh Salem Alkahtani

    2016-12-01

    Full Text Available Human rights constitute a significant aspect of the law. Human rights are protected by national and international legal and judicial apparatuses. In addition, promoting respect for human rights is a key purpose of the United Nations (UN and its international bodies, such as the UN Human Rights Council, established in 2006, and the International Criminal Court, created in 1998. The UN has also issued a variety of protocols, declarations and agreements regarding human rights and their protection, specifically the Universal Declaration of Human Rights in 1948 and the International Convention on Civil and Political Rights in 1966. In the Kingdom of Saudi Arabia, Saudi legislation has initiated and allowed various Saudi human rights institutions, namely the Saudi Human Rights Commission and Saudi National Society for Human Rights. In particular, Saudi legislation has focused on Sharia principles when it comes to the interpretation and implementation of secular international human rights laws. Saudi legislation has enacted a variety of contemporary human rights laws, including the Child Protection Law and the Law of Protection from Abuse. The human cost of terrorism has been felt virtually in every part of the globe. Terrorism has disrupted peace, security, liberty and physical integrity of individuals at every level. Protection and security of its individuals is a fundamental obligation of the state. Accordingly, the Kingdom of Saudi Arabia has taken several legal measures, allowed under Islamic Sharia and International laws, to ensure the protection of human rights of its citizens and residents and safeguard the society against possible threats of terrorism and bring the criminals to justice. Saudi legislation has ensured human rights applications in other Saudi criminal laws, such as the Saudi Criminal Procedure Law of 2002, amended in 2014 (hereinafter SCPL, and the Saudi Law of Terrorist Crimes of 2014 (hereinafter SLTC. This short commentary

  20. Ceftriaxone protects against the neurotoxicity of human immunodeficiency virus proteins.

    Science.gov (United States)

    Rumbaugh, Jeffrey A; Li, Guanhan; Rothstein, Jeffrey; Nath, Avindra

    2007-04-01

    Human immunodeficiency virus (HIV) proteins Tat and gp120 have been implicated in the pathogenesis of HIV dementia by various mechanisms, including down-regulation of excitatory amino acid transporter-2 (EAAT2), which is responsible for inactivation of synaptic glutamate. Recent work indicates that beta-lactam antibiotics are potent stimulators of EAAT2 expression. The authors treated mixed human fetal neuronal cultures with recombinant gp120 or Tat, in the presence or absence of ceftriaxone, and determined neurotoxicity by measuring mitochondrial membrane potential and neuronal cell death. Ceftriaxone produced dose-dependent attenuation of the neurotoxicity and neuronal cell death caused by both viral proteins. This study demonstrates that this class of drugs may have therapeutic efficacy in HIV dementia.

  1. Fall Protection Characteristics of Safety Belts and Human Impact Tolerance.

    Science.gov (United States)

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-08-23

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt1), which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness2, 3), which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference4-9) to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model10) was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

  2. Fall protection characteristics of safety belts and human impact tolerance.

    Science.gov (United States)

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-01-01

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt, which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness, which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

  3. Human capital use, innovation, patent protection, and economic growth in multiple regions

    NARCIS (Netherlands)

    Batabyal, A.; Nijkamp, P.

    2013-01-01

    We provide the first theoretical analysis of the effects of human capital use, innovative activity, and patent protection, on economic growth in a model with many regions. In each region, consumers have constant relative risk-aversion preferences, there is no human capital growth, and there are

  4. HEW Proposed Policy on the Protection of Human Subjects: Experimentation and the Institutionalized Mentally Disabled

    Science.gov (United States)

    Washington University Law Quarterly, 1975

    1975-01-01

    Underlying bases for federal interest in experimentation on human subjects, including abuses of investigative processes and efforts at regulation, are explored. Focus is on recent HEW rules on the protection of human subjects, which will have a significant impact on many research institutions. (LBH)

  5. TOWARDS THE PROTECTION OF HUMAN RIGHTS: DO THE NEW ZIMBABWEAN CONSTITUTIONAL PROVISIONS ON JUDICIAL INDEPENDENCE SUFFICE?

    Directory of Open Access Journals (Sweden)

    Lovemore Chiduza

    2014-04-01

    Full Text Available If human rights are to be effectively protected in any country, the judiciary has to recognise that it also has a role to play in this regard. The rationale for this is that the judiciary has a duty to enhance and protect human rights. Across Africa and most notably in Zimbabwe political interference has been noted as a factor that limits judicial independence. In Zimbabwe the weak protection of judicial independence has contributed to gross human rights violations. Constitutional reforms have been conducted in order to improve the independence of the judiciary and consequently the judicial protection of human rights. These efforts have resulted in the adoption of a new Constitution in Zimbabwe which has replaced the Lancaster House Constitution. The Constitutional reforms have captured legal principles which will ensure an improvement in the human rights situation. Key to the reforms has been the independence of the judiciary. The Constitution guarantees the independence of the judiciary. Despite such guarantees there are a number of challenges with regards to this independence. The aim of this paper is therefore to analyse the judicial reforms introduced by the Constitution of Zimbabwe with a view to establishing whether or not such reforms are likely to improve judicial independence and in turn the protection of human rights in Zimbabwe.

  6. Fall Protection Characteristics of Safety Belts and Human Impact Tolerance

    OpenAIRE

    HINO, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-01-01

    Abstract: Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt1 ), which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness2, 3 ), which has been used in many other countries. To determine human tolerance for ...

  7. Advances on human milk hormones and protection against obesity.

    Science.gov (United States)

    Savino, F; Benetti, S; Liguori, S A; Sorrenti, M; Cordero Di Montezemolo, L

    2013-11-03

    Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

  8. Heat Exchange in “Human body - Thermal protection - Environment” System

    Science.gov (United States)

    Khromova, I. V.

    2017-11-01

    This article is devoted to the issues of simulation and calculation of thermal processes in the system called “Human body – Thermal protection - Environment” under low temperature conditions. It considers internal heat sources and convective heat transfer between calculated elements. Overall this is important for the Heat Transfer Theory. The article introduces complex heat transfer calculation method and local thermophysical parameters calculation method in the system called «Human body – Thermal protection – Environment», considering passive and active thermal protections, thermophysical and geometric properties of calculated elements in a wide range of environmental parameters (water, air). It also includes research on the influence that thermal resistance of modern materials, used in special protective clothes development, has on heat transfer in the system “Human body – Thermal protection – Environment”. Analysis of the obtained results allows adding of the computer research data to experiments and optimizing of individual life-support system elements, which are intended to protect human body from exposure to external factors.

  9. Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva

    Science.gov (United States)

    Baumann, T.; Kozik, J.; Lussi, A.; Carvalho, T. S.

    2016-10-01

    During dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing only ions (AS), human saliva dialysed against artificial saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed against deionised water, containing only salivary proteins but no ions (HS/DW). Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS, HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During the cycling process, the surface hardness and the calcium released from the surface of the specimens were measured. The different kinds of saliva provided different levels of protection, HS/DW exhibiting significantly better protection than all the other groups (p saliva, therefore, have different effects on the protective properties of the pellicle and the right proportions of these components in saliva are critical for the ability to form a protective pellicle.

  10. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  11. A Path to Planetary Protection Requirements for Human Exploration: A Literature Review and Systems Engineering Approach

    Science.gov (United States)

    Johnson, James E.; Conley, Cassie; Siegel, Bette

    2015-01-01

    As systems, technologies, and plans for the human exploration of Mars and other destinations beyond low Earth orbit begin to coalesce, it is imperative that frequent and early consideration is given to how planetary protection practices and policy will be upheld. While the development of formal planetary protection requirements for future human space systems and operations may still be a few years from fruition, guidance to appropriately influence mission and system design will be needed soon to avoid costly design and operational changes. The path to constructing such requirements is a journey that espouses key systems engineering practices of understanding shared goals, objectives and concerns, identifying key stakeholders, and iterating a draft requirement set to gain community consensus. This paper traces through each of these practices, beginning with a literature review of nearly three decades of publications addressing planetary protection concerns with respect to human exploration. Key goals, objectives and concerns, particularly with respect to notional requirements, required studies and research, and technology development needs have been compiled and categorized to provide a current 'state of knowledge'. This information, combined with the identification of key stakeholders in upholding planetary protection concerns for human missions, has yielded a draft requirement set that might feed future iteration among space system designers, exploration scientists, and the mission operations community. Combining the information collected with a proposed forward path will hopefully yield a mutually agreeable set of timely, verifiable, and practical requirements for human space exploration that will uphold international commitment to planetary protection.

  12. Protection from psychosocial risks at work under the European Convention on Human Rights: is it possible?

    Science.gov (United States)

    Sychenko, Elena

    2016-09-01

    This paper argues the possibility of establishing common principles of protection from psychosocial risks (PSR) on the basis of the legal positions of the European Court of Human Rights (the Court) expressed in recent cases on degrading treatment and occupational health. The author focuses on the positive obligations of the States to ensure the protection of the right for life and of the right to respect for private life. The prohibition of degrading treatment in relations between private persons is also considered as relevant to the issue of the protection from PSR. Analyzing the Court's case law (judgments of the Court) we substantiate the possibility of claiming protection from PSR under the European Convention on Human Rights, namely, articles 2, 3 and 6, 8.

  13. Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions Workshop Booklet - 2015

    Science.gov (United States)

    Fonda, Mark L.

    2015-01-01

    Although NASA's preparations for the Apollo lunar missions had only a limited time to consider issues associated with the protection of the Moon from biological contamination and the quarantine of the astronauts returning to Earth, they learned many valuable lessons (both positive and negative) in the process. As such, those efforts represent the baseline of planetary protection preparations for sending humans to Mars. Neither the post-Apollo experience or the Shuttle and other follow-on missions of either the US or Russian human spaceflight programs could add many additional insights to that baseline. Current mission designers have had the intervening four decades for their consideration, and in that time there has been much learned about human-associated microbes, about Mars, and about humans in space that has helped prepare us for a broad spectrum of considerations regarding potential biological contamination in human Mars missions and how to control it. This paper will review the approaches used in getting this far, and highlight some implications of this history for the future development of planetary protection provisions for human missions to Mars. The role of NASA and ESA's planetary protection offices, and the aegis of COSPAR have been particularly important in the ongoing process.

  14. Protecting human dignity: reframing the abortion debate to respect the dignity of choice and life

    OpenAIRE

    Halliday, S.

    2016-01-01

    The Abortion Act 1967 constructs women as patients seeking care, rather than as women choosing abortion, portraying them as vulnerable subjects in need of assistance to make a responsible decision. This article reviews recent proposed women-protective amendments to the Abortion Act focussing upon the proposed introduction of a requirement that women be offered independent counselling. It argues that the issue of abortion should be reframed as a matter of the protection of human dignity, rathe...

  15. Rethinking Data Sharing and Human Participant Protection in Social Science Research: Applications from the Qualitative Realm

    Directory of Open Access Journals (Sweden)

    Dessi Kirilova

    2017-09-01

    Full Text Available While data sharing is becoming increasingly common in quantitative social inquiry, qualitative data are rarely shared. One factor inhibiting data sharing is a concern about human participant protections and privacy. Protecting the confidentiality and safety of research participants is a concern for both quantitative and qualitative researchers, but it raises specific concerns within the epistemic context of qualitative research. Thus, the applicability of emerging protection models from the quantitative realm must be carefully evaluated for application to the qualitative realm. At the same time, qualitative scholars already employ a variety of strategies for human-participant protection implicitly or informally during the research process. In this practice paper, we assess available strategies for protecting human participants and how they can be deployed. We describe a spectrum of possible data management options, such as de-identification and applying access controls, including some already employed by the Qualitative Data Repository (QDR in tandem with its pilot depositors. Throughout the discussion, we consider the tension between modifying data or restricting access to them, and retaining their analytic value. We argue that developing explicit guidelines for sharing qualitative data generated through interaction with humans will allow scholars to address privacy concerns and increase the secondary use of their data.

  16. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  17. Protection of the right to privacy in the practice of the European Court of Human Rights

    Directory of Open Access Journals (Sweden)

    Mladenov Marijana

    2013-01-01

    Full Text Available The right to privacy is a fundamental human right and an essential component of the protection of human autonomy and freedom. The development of science and information systems creates various opportunities for interferences with physical and moral integrity of a person. Therefore, it is necessary to determine the precise content of the right to privacy. The European Convention on Human Rights and Fundamental Freedoms guarantees this right under Article 8. The European Court of Human Rights did not precisely define the content of the right to privacy and thereby the applicants could bring different aspects of life into the scope of respect for private life. According to the Court, the concept of privacy and private life includes the following areas of human life: the right to establish and maintain relationships with other human beings, protection of the physical and moral integrity of persons, protection of personal data, change of personal name, various issues related to sexual orientation and transgender. The subject of this paper is referring to previously mentioned spheres of human life in the light of interpretation of Article 8 of the Convention.

  18. The protection of the accused in international criminal law according to the Human Rights Law Standard

    Directory of Open Access Journals (Sweden)

    Karolina Kremens

    2011-12-01

    Full Text Available The presented paper discusses the influence of international human rights law on international criminal law. It tries to give an answer to the question of whether rules protecting the accused in international criminal proceedings meet the human rights law standard provided by international declarations and covenants. Meaning, if the proceedings before the International Criminal Tribunal for Former Yugoslavia (ICTY, International Criminal Tribunal for Rwanda (ICTR and International Criminal Court (ICC meet the standard provided by international human rights law, in particular the International Covenant on Civil and Political Rights. The paper proves that international human rights law has affected international criminal law tremendously. Moreover, it is argued that the protection of the accused in the law of the international courts and tribunals with regard to his rights has improved when compared to the international human rights law standard. In particular the Rome Statute of the ICC provides the accused with the most comprehensive protection. This is especially visible in the case of such rights as the presumption of innocence, right to an interpreter and right to remain silent. Nevertheless, some shortcomings in the law of the ad hoc tribunals and ICC can be observed, in particular when it comes to identifying the commencement of protection of the accused.

  19. The indivisibility of human rights and the Decent Work Protection in a Globalized World

    Directory of Open Access Journals (Sweden)

    Lourival José de Oliveira

    2016-05-01

    Full Text Available The initial premise is limited to the finding that the production procedures interna- tionalized. Consequently, from the production sharing or defined spaces, was obtained as one of the main results the precariousness of human labor, considering that at the natio- nal level, given the liberalizing policies, is not making it possible to ensure the national state minimum safeguards to protect the work. To address this reality, this paper proposes the construction of new public spaces, with the participation of several international actors, no longer confining to existing international public entities, and the protection of human work should be promoted, provided as a human right and a fundamental right, taking into account the global context and the thematic multidisciplinary. It is the job of the holistic view, which assumes the interdependence and indivisibility of human rights as a prerequisite in order to balance economic development with social development internationally.

  20. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans.

    Science.gov (United States)

    Newburg, D S

    2009-04-01

    This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These

  1. Exercise training protects human and rodent β cells against endoplasmic reticulum stress and apoptosis.

    Science.gov (United States)

    Paula, Flavia M M; Leite, Nayara C; Borck, Patricia C; Freitas-Dias, Ricardo; Cnop, Miriam; Chacon-Mikahil, Mara P T; Cavaglieri, Claudia R; Marchetti, Piero; Boschero, Antonio C; Zoppi, Claudio C; Eizirik, Decio L

    2017-11-13

    Prolonged exercise has positive metabolic effects in obese or diabetic individuals. These effects are usually ascribed to improvements in insulin sensitivity. We evaluated whether exercise also generates circulating signals that protect human and rodent β cells against endoplasmic reticulum (ER) stress and apoptosis. For this purpose, we obtained serum from humans or mice before and after an 8 wk training period. Exposure of human islets or mouse or rat β cells to human or rodent sera, respectively, obtained from trained individuals reduced cytokine (IL-1β+IFN-γ)- or chemical ER stressor-induced β-cell ER stress and apoptosis, at least in part via activation of the transcription factor STAT3. These findings indicate that exercise training improves human and rodent β-cell survival under diabetogenic conditions and support lifestyle interventions as a protective approach for both type 1 and 2 diabetes.-Paula, F. M. M., Leite, N. C., Borck, P. C., Freitas-Dias, R., Cnop, M., Chacon-Mikahil, M. P. T., Cavaglieri, C. R., Marchetti, P., Boschero, A. C., Zoppi, C. C., Eizirik, D. L. Exercise training protects human and rodent β cells against endoplasmic reticulum stress and apoptosis. © FASEB.

  2. Protecting the Home and Adequate Housing - Living in a Caravan or Trailer as a Human Right

    NARCIS (Netherlands)

    Donders, Y.

    2016-01-01

    Many Roma, gypsies and travellers live in caravans or trailers, sometimes in together trailer parks or camps. This article analyses how this specific lifestyle connected to their housing is protected under the various regimes and provisions of international human rights law. Home and adequate

  3. Analyzing risks to protected areas using the human modification framework: a Colorado case study

    Science.gov (United States)

    David M. Theobald; Alisa Wade; Grant Wilcox; Nate. Peterson

    2010-01-01

    A framework that organizes natural and protected areas is often used to help understand the potential risks to natural areas and aspects of their ecological and human dimensions. The spatial (or landscape) context of these dynamics is also a critical, but, rarely considered, factor. Common classification systems include the U.S. Geological (USGS) Gap Analysis Program...

  4. Research monitoring by US medical institutions to protect human subjects: compliance or quality improvement?

    NARCIS (Netherlands)

    de Jong, Jean Philippe; van Zwieten, Myra C. B.; Willems, Dick L.

    2013-01-01

    In recent years, to protect the rights and welfare of human subjects, institutions in the USA have begun to set up programmes to monitor ongoing medical research. These programmes provide routine, onsite oversight, and thus go beyond existing oversight such as investigating suspected misconduct or

  5. Hendra virus vaccine, a one health approach to protecting horse, human, and environmental health.

    Science.gov (United States)

    Middleton, Deborah; Pallister, Jackie; Klein, Reuben; Feng, Yan-Ru; Haining, Jessica; Arkinstall, Rachel; Frazer, Leah; Huang, Jin-An; Edwards, Nigel; Wareing, Mark; Elhay, Martin; Hashmi, Zia; Bingham, John; Yamada, Manabu; Johnson, Dayna; White, John; Foord, Adam; Heine, Hans G; Marsh, Glenn A; Broder, Christopher C; Wang, Lin-Fa

    2014-03-01

    In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.

  6. Spotted hyaena space use in relation to human infrastructure inside a protected area

    Directory of Open Access Journals (Sweden)

    Lydia E. Belton

    2016-10-01

    Full Text Available Increasing human population growth has led to elevated levels of human-carnivore conflict. However, some carnivore populations have adapted to urban environments and the resources they supply. Such associations may influence carnivore ecology, behaviour and life-history. Pockets of urbanisation sometimes occur within protected areas, so that anthropogenic influences on carnivore biology are not necessarily confined to unprotected areas. In this study we evaluated associations between human infrastructure and related activity and space use of spotted hyaenas within one of the largest protected areas in South Africa, the Kruger National Park. Home range size was smaller for the dominant female of a clan living in close proximity to humans than that of the dominant female of a clan without direct access to human infrastructure. The home range including human infrastructure was also used less evenly during the night, presumably when the animals were active. Within this home range, a village area was preferred during the night, when the least modified areas within the village were preferred and administration and highly modified areas were avoided. During the day, however, there were no preference or avoidance of the village area, but all habitats except unmodified habitats within the village area were avoided. We suggest that human infrastructure and associated activity influenced hyaena space use, primarily through alterations in the spatial distribution of food. However, these effects may have been indirectly caused by habitat modification that generated favourable hunting habitat rather than a direct effect caused by access to human food such as garbage. Because of the often pivotal effects of apex predators in terrestrial ecosystems, we encourage further work aimed to quantify how human presence influences large carnivores and associated ecosystem processes within protected areas.

  7. Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Lindsay Crickard

    Full Text Available Smallpox (variola virus is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs against vaccinia H3 (H3L and B5 (B5R, targeting both the mature virion (MV and extracellular enveloped virion (EV forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP studies examining severe combined immunodeficiency mice (SCID given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG. Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV. In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.

  8. Protection of non-human primates against rabies with an adenovirus recombinant vaccine.

    Science.gov (United States)

    Xiang, Z Q; Greenberg, L; Ertl, H C; Rupprecht, C E

    2014-02-01

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

    Science.gov (United States)

    Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

    2014-01-01

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. PMID:24503087

  10. The Content Of Legal Relationship On The Implementation Of Human Rights And Citizen Protection By The Bodies Of Judicial Authority

    Directory of Open Access Journals (Sweden)

    Badma V. Sangadzhiev

    2015-01-01

    Full Text Available In the present article authors consider concepts of human rights, analyze content of legal relationship on the implementation of actions for protection of human rights and citizen by bodies of judicial authority

  11. Universal System of Human Rights Protection: analysis of the reports of the Human Rights Committee in Latin America

    Directory of Open Access Journals (Sweden)

    Karen Giovanna Añaños Bedriñana

    2016-06-01

    Full Text Available The aim of this article is to know the structures and the functioning of the universal system of human rights protection and to analyze the different types of violation of human rights in Latin America region, reflected in the Reports of the Human Rights Committee of the United Nations. These Reports expose the progresses and difficulties in the application of the International Convention on Civil and Political Rights by states, in further violation of human rights become visible. These are observed, in general, in the case of women, penitentiary conditions of the prisoners, fragile groups, impunity of those responsible, and so on, likewise a specific analysis is done in some countries additional questions. In summary, it is attempted to issue a series of suggestions and recommendations with the purpose to improve the application of the Covenant and to provide the basis for Peace Research, whose benefits will impact on the whole society and the citizens of these countries.

  12. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

  13. Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells.

    Science.gov (United States)

    Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

    2013-10-15

    Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. Copyright © 2013. Published by Elsevier Inc.

  14. Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

    Science.gov (United States)

    Gavella, Mirjana; Lipovac, Vaskresenija

    2013-01-01

    This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane. PMID:23503425

  15. Melissa Officinalis L. Extracts Protect Human Retinal Pigment Epithelial Cells against Oxidative Stress-Induced Apoptosis.

    Science.gov (United States)

    Jeung, In Cheul; Jee, Donghyun; Rho, Chang-Rae; Kang, Seungbum

    2016-01-01

    We evaluated the protective effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) against oxidative stress-induced apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). ARPE-19 cells were incubated with ALS-L1023 for 24 h and then treated with hydrogen peroxide (H2O2). Oxidative stress-induced apoptosis and intracellular generation of reactive oxygen species (ROS) were assessed by flow cytometry. Caspase-3/7 activation and cleaved poly ADP-ribose polymerase (PARP) were measured to investigate the protective role of ALS-L1023 against apoptosis. The protective effect of ALS-L1023 against oxidative stress through activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was evaluated by Western blot analysis. ALS-L1023 clearly reduced H2O2-induced cell apoptosis and intracellular production of ROS. H2O2-induced oxidative stress increased caspase-3/7 activity and apoptotic PARP cleavage, which were significantly inhibited by ALS-L1023. Activation of the PI3K/Akt pathway was associated with the protective effect of ALS-L1023 on ARPE-19 cells. ALS-L1023 protected human RPE cells against oxidative damage. This suggests that ALS-L1023 has therapeutic potential for the prevention of dry age-related macular degeneration.

  16. Review (laws for compliance and human rights multi-level protection in Inter-American Human Rights System

    Directory of Open Access Journals (Sweden)

    Natalia Torres Zúñiga

    2013-12-01

    Full Text Available This article addresses diverse perspectives concerning relationship between reviewing (laws for compliance and the process of putting international law of human rights on a constitutional footing. Therefore, a parallel is established between reviewing (laws for compliance and constitutional review (laws in order to outline features and application impact of this research. The design of a multi-level protection system for fundamental rights in Latin America is also discussed in this article.

  17. Should protections for research with humans who cannot consent apply to research with nonhuman primates?

    Science.gov (United States)

    Wendler, David

    2017-01-01

    Research studies and interventions sometimes offer potential benefits to subjects that compensate for the risks they face. Other studies and interventions, which I refer to as “nonbeneficial” research, do not offer subjects a compensating potential for benefit. These studies and interventions have the potential to exploit subjects for the benefit of others, a concern that is especially acute when investigators enroll individuals who are unable to give informed consent. US regulations for research with human subjects attempt to address this concern by mandating strict protections for nonbeneficial research with subjects who cannot consent. Typically, humans who cannot consent, such as children, may be enrolled in nonbeneficial research only when it poses low risks and has the potential to gather information of sufficient value to justify the risks, an appropriate surrogate gives permission on the individual’s behalf and the individual agrees (assents). In contrast, US regulations for nonbeneficial research with nonhuman primates do not include these protections, even though it too involves subjects who cannot consent and who face risks for the benefit of others. Is this difference in regulatory protections justified? Or does the principle of fairness—treat like cases alike—imply that regulations for nonbeneficial research with nonhuman primates should include protections similar to those that apply to nonbeneficial research with humans who cannot consent? PMID:24647873

  18. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    Science.gov (United States)

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-04

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases. Copyright © 2015, American Association for the Advancement of Science.

  19. Human anti-plague monoclonal antibodies protect mice from Yersinia pestis in a bubonic plague model.

    Directory of Open Access Journals (Sweden)

    Xiaodong Xiao

    2010-10-01

    Full Text Available Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252 and two anti-V-specific human mAb (m253, m254 by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.

  20. Protecting Children Victims of Crimes of Human Trafficking in the EU

    Directory of Open Access Journals (Sweden)

    Minodora-Ioana Balan-Rusu

    2013-08-01

    Full Text Available Within the paper there were examined the main provisions of the European legislative act framework in the domain of protecting children victims of human trafficking offenses, with some critical remarks. The paper can be useful to the European and Romanian legislator, practitioners and academics in the field. The novelty consists of analyzing the provisions of the European legislative act, focusing on the practical ways provided for the protection of children victims of this kind of crime, and the formulated critical remarks.

  1. CB2 receptor agonists protect human dopaminergic neurons against damage from HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Shuxian Hu

    Full Text Available Despite the therapeutic impact of anti-retroviral therapy, HIV-1-associated neurocognitive disorder (HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Recent work suggests that the nigrostriatal dopaminergic area is a critical brain region for the neuronal dysfunction and death seen in HAND and that human dopaminergic neurons have a particular sensitivity to gp120-induced damage, manifested as reduced function (decreased dopamine uptake, morphological changes, and reduced viability. Synthetic cannabinoids inhibit HIV-1 expression in human microglia, suppress production of inflammatory mediators in human astrocytes, and there is substantial literature demonstrating the neuroprotective properties of cannabinoids in other neuropathogenic processes. Based on these data, experiments were designed to test the hypothesis that synthetic cannabinoids will protect dopaminergic neurons against the toxic effects of the HIV-1 protein gp120. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, we were able to show that the CB1/CB2 agonist WIN55,212-2 blunts gp120-induced neuronal damage as measured by dopamine transporter function, apoptosis and lipid peroxidation; these actions were mediated principally by the CB2 receptor. Adding supplementary human microglia to our cultures enhances gp120-induced damage; WIN55,212-2 is able to alleviate this enhanced damage. Additionally, WIN55,212-2 inhibits gp120-induced superoxide production by purified human microglial cells, inhibits migration of human microglia towards supernatants generated from gp120-stimulated human mesencephalic neuronal/glial cultures and reduces chemokine and cytokine production from the human mesencephalic neuronal/glial cultures. These data suggest that synthetic cannabinoids are capable of protecting human dopaminergic neurons from

  2. Two-dose strategies for human papillomavirus vaccination: how well do they need to protect?

    Science.gov (United States)

    Jit, Mark; Choi, Yoon Hong; Laprise, Jean-François; Boily, Marie-Claude; Drolet, Mélanie; Brisson, Marc

    2014-05-30

    Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown. Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence. Models suggest that at 40-80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada) with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with 10 years two-dose protection. Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Strengthening the human rights framework to protect breastfeeding: a focus on CEDAW.

    Science.gov (United States)

    Galtry, Judith

    2015-01-01

    There have been recent calls for increased recognition of breastfeeding as a human right. The United Nations Convention on the Elimination of All Forms of Discrimination against Women, 1979 (CEDAW) is the core human rights treaty on women. CEDAW's approach to breastfeeding is considered from an historical perspective. A comparison is drawn with breastfeeding protection previously outlined in the International Labour Organization's Maternity Protection Convention, 1919 (ILO C3), and its 1952 revision (ILO C103), and subsequently, in the United Nations Convention on the Rights of the Child, 1989 (CRC). Despite breastfeeding's sex-specific significance to an international human rights treaty on women and CEDAW's emphasis on facilitating women's employment, CEDAW is, in reality, a relatively weak instrument for breastfeeding protection. In both its text and subsequent interpretations explicit recognition of breastfeeding is minimal or nonexistent. Explanations for this are proposed and contextualised in relation to various political, social and economic forces, especially those influencing notions of gender equality. During the mid to late 1970s -when CEDAW was formulated - breastfeeding posed a strategic challenge for key feminist goals, particularly those of equal employment opportunity, gender neutral childrearing policy and reproductive rights. Protective legislation aimed at working women had been rejected as outdated and oppressive. Moreover, the right of women to breastfeed was generally assumed, with choice over infant feeding practices often perceived as the right NOT to breastfeed. There was also little awareness or analysis of the various structural obstacles to breastfeeding's practice, such as lack of workplace support, that undermine 'choice'. Subsequent interpretations of CEDAW show that despite significant advances in scientific and epidemiological knowledge about breastfeeding's importance for short-term and long-term maternal health, breastfeeding

  4. Nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, protects against Shiga toxin cytotoxicity in human microvascular endothelial cells.

    Science.gov (United States)

    Ohmi, K; Kiyokawa, N; Sekino, T; Suzuki, T; Mimori, K; Taguchi, T; Nakajima, H; Katagiri, Y U; Fujimoto, J; Nakao, H; Takeda, T

    2001-01-01

    Infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause microvascular endothelial cell damage, resulting in hemorrhagic colitis and hemolytic uremic syndrome. The prevention of endothelial cell damage is therefore a crucial step in overcoming this disorder. Here, we report that nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, has a protective effect against the cytotoxicity of Stxs in human microvascular endothelial cells (HMVECs). The relative viability of cells treated with 1.5-15 pM of Stx1 was reduced to 10-20% of that without Stx1. However, the viability of cells treated with NBT (10-100 microM) remained higher than 80%, even in the presence of Stx1. NBT also protected against Stx1 cytotoxicity in sodium butyrate-treated hypersensitive HMVECs. The protective effect of NBT against Stx cytotoxicity may be due to the depletion of ATP in the cells, thereby inhibiting the entry of Stx1.

  5. Elemene injection induced autophagy protects human hepatoma cancer cells from starvation and undergoing apoptosis.

    Science.gov (United States)

    Lin, Yan; Wang, Keming; Hu, Chunping; Lin, Lin; Qin, Shukui; Cai, Xueting

    2014-01-01

    Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anticancer effects against a broad spectrum of tumors. In an in vivo experiment, we found that apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2, combined with elemene injection (Ele) for the treatment of H22 solid tumor in mice resulted in worse effectiveness than apatinib alone. Moreover, Ele could protect HepG2 cells from death induced by serum-free starvation. Further data on the mechanism study revealed that Ele induced protective autophagy and prevented human hepatoma cancer cells from undergoing apoptosis. Proapoptosis effect of Ele was enhanced when proautophagy effect was inhibited by hydroxychloroquine. Above all, Ele has the effect of protecting cancer cells from death either in apatinib induced nutrient deficient environment or in serum-free induced starvation. A combination of elemene injection with autophagy inhibitor might thus be a useful therapeutic option for hepatocellular carcinoma.

  6. Ascorbic acid inhibits human insulin aggregation and protects against amyloid induced cytotoxicity.

    Science.gov (United States)

    Alam, Parvez; Beg, Ayesha Zainab; Siddiqi, Mohammad Khursheed; Chaturvedi, Sumit Kumar; Rajpoot, Ravi Kant; Ajmal, Mohd Rehan; Zaman, Masihuz; Abdelhameed, Ali S; Khan, Rizwan Hasan

    2017-05-01

    Protein aggregation into oligomers and fibrils are associated with many human pathophysiologies. Compounds that modulate protein aggregation and interact with preformed fibrils and convert them to less toxic species, expect to serve as promising drug candidates and aid to the drug development efforts against aggregation diseases. In present study, the kinetics of amyloid fibril formation by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA) were investigated by employing various spectroscopic, imaging and computational approaches. We demonstrate that ascorbic acid significantly inhibits the fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid destabilise the preformed amyloid fibrils and protects human neuroblastoma cell line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies the role of ascorbic acid that can serve as potential molecule in preventing human insulin aggregation and associated pathophysiologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage.

    Science.gov (United States)

    Mitsi, E; Roche, A M; Reiné, J; Zangari, T; Owugha, J T; Pennington, S H; Gritzfeld, J F; Wright, A D; Collins, A M; van Selm, S; de Jonge, M I; Gordon, S B; Weiser, J N; Ferreira, D M

    2017-03-01

    The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.

  8. The evolution of the Constitutional Protection of Women’s Human Rights in Colombia

    Directory of Open Access Journals (Sweden)

    Sandra MORENO FLÓREZ

    2011-04-01

    Full Text Available Human rights were first acknowledged in Colombia in the 1991 Constitution, bringing up a catalogue of specific rights in favour of the female population whose implementation has been possible thanks to the Constitutional Court’s decisive compromise on the struggle against gender discrimination. This way, since the incorporation of the gender perspective in the Colombian Law, great progress has been obtained in the effectiveness of the constitutional normative framework and in the consequent effective protection of women’s human rights in legally relevant different ambits of life.

  9. The Human Right to Adequate Housing: A Tool for Promoting and Protecting Individual and Community Health

    Science.gov (United States)

    Thiele, Bret

    2002-01-01

    The human right to adequate housing is enshrined in international law. The right to adequate housing can be traced to the Universal Declaration of Human Rights, which was unanimously adopted by the world community in 1948. Since that time, the right to adequate housing has been reaffirmed on numerous occasions and further defined and elaborated. A key component of this right is habitability of housing, which should comply with health and safety standards. Therefore, the right to adequate housing provides an additional tool for advocates and others interested in promoting healthful housing and living conditions and thereby protecting individual and community health. PMID:11988432

  10. Are Protected Areas Required to Maintain Functional Diversity in Human-Modified Landscapes?

    OpenAIRE

    Cottee-Jones, H. Eden W.; Matthews, Thomas J.; Bregman, Tom P.; Barua, Maan; Tamuly, Jatin; Whittaker, Robert J.

    2015-01-01

    The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropic...

  11. A decision model for the sustainable protection of human rights in Italian Prison System

    Directory of Open Access Journals (Sweden)

    Antonio Maturo

    2014-12-01

    Full Text Available The work starts from an analysis of the critical problems of the prison system in Italy. It aims to develop a decision-making model to address the issue of sustainable protection of human rights in prisons. It shows how, using the Saaty AHP procedure, it is possible to have an analytical reasoning guideline for the understanding of the validity of the various alternative choices, in order to facilitate the situation of the prisoners and their reintegration into society.

  12. Protective effect of a Phyllanthus orbicularis aqueous extract against UVB light in human cells.

    Science.gov (United States)

    Vernhes, Marioly; González-Pumariega, Maribel; Andrade, Luciana; Schuch, Andre Passaglia; de Lima-Bessa, Keronninn Moreno; Menck, Carlos Frederico Martins; Sánchez-Lamar, Angel

    2013-01-01

    One approach to protect human skin against the dangerous effects of solar ultraviolet (UV) irradiation is the use of natural products, such as photoprotectors. Phyllanthus orbicularis Kunth (Euphorbiaceae) is a Cuban endemic plant used in popular medicine. Its antigenotoxicity effect against some harmful agents has been investigated. However, the effect in ultraviolet B (UVB)-irradiated human cells has not been previously assessed. The protective effect of a P. orbicularis extract against UVB light-induced damage in human cells was evaluated. DNA repair proficient (MRC5-SV) and deficient (XP4PA, complementation group XPC) cell-lines were used. Damaging effects of UVB light were evaluated by clonogenic assay and apoptosis induction by flow cytometry techniques. The extent of DNA repair itself was determined by the removal of cyclobutane pyrimidine dimers (CPDs). The CPDs were detected and quantified by slot-blot assay. Treatment of UVB-irradiated MRC5-SV cells with P. orbicularis extract increased the percentage of colony-forming cells from 36.03 ± 3.59 and 4.42 ± 1.45 to 53.14 ± 8.8 and 14.52 ± 1.97, for 400 and 600 J/m(2), respectively. A decrease in apoptotic cell population was observed in cells maintained within the extract. The P. orbicularis extract enhanced the removal of CPD from genomic DNA. The CPDs remaining were found to be about 27.7 and 1.1%, while with plant extract, treatment these values decreased to 16.1 and 0.2%, for 3 and 24 h, respectively. P. orbicularis aqueous extract protects human cells against UVB damage. This protective effect is through the modulation of DNA repair effectiveness.

  13. The environmental protection in the jurisprudence of the Inter-American Court of Human Rights

    Directory of Open Access Journals (Sweden)

    Valerio de Oliveira Mazzuoli

    2015-09-01

    Full Text Available This article examines the interconnections between environmental issues and the protection of human rights, in a process that began in the United Nations Conference on the Human Environment (Stockholm, 1972 and has been developed by the greening of the regional human rights systems. In the Inter-American system the article 11 of the Additional Protocol to the American Convention on Economic, Social and Cultural Rights of 1988 — the Protocol of San Salvador — guarantees the right to a healthy environment. However the American Convention (on its arts. 3-25, 44-51 and 61-69 and its Additional Protocol (on its arts. 8, 13 and 19.6 only allow the submission of individual petitions to the Inter-American Commission and the possible acting of the Inter-American Court, in complaints containing alleged violations of civil and political rights, trade union rights and the right to education. Despite the lack of devices that are capable to ensure an effective protection to the right to a healthy environment, by itself, the Inter-American Court has demonstrated the greening of the human rights, which means, in other words, that it is quite possible to protect environmental issues by the demonstration of its interconnections with civil and political rights that are directly protected by the inter-American system. Therefore, it is necessary to understand the contributions of the jurisprudence of the Inter-American Court in the strengthening of the civil and political rights in cases related to environmental issues.

  14. Integrating habitat status, human population pressure, and protection status into biodiversity conservation priority setting

    Science.gov (United States)

    Shi, H.; Singh, A.; Kant, S.; Zhu, Z.; Waller, E.

    2005-01-01

    Priority setting is an essential component of biodiversity conservation. Existing methods to identify priority areas for conservation have focused almost entirely on biological factors. We suggest a new relative ranking method for identifying priority conservation areas that integrates both biological and social aspects. It is based on the following criteria: the habitat's status, human population pressure, human efforts to protect habitat, and number of endemic plant and vertebrate species. We used this method to rank 25 hotspots, 17 megadiverse countries, and the hotspots within each megadiverse country. We used consistent, comprehensive, georeferenced, and multiband data sets and analytical remote sensing and geographic information system tools to quantify habitat status, human population pressure, and protection status. The ranking suggests that the Philippines, Atlantic Forest, Mediterranean Basin, Caribbean Islands, Caucasus, and Indo-Burma are the hottest hotspots and that China, the Philippines, and India are the hottest megadiverse countries. The great variation in terms of habitat, protected areas, and population pressure among the hotspots, the megadiverse countries, and the hotspots within the same country suggests the need for hotspot- and country-specific conservation policies.

  15. The importance of human FcgammaRI in mediating protection to malaria.

    Directory of Open Access Journals (Sweden)

    Richard S McIntosh

    2007-05-01

    Full Text Available The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria. We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults. Although these novel reagents bind with strong affinity to malaria parasites, it remains unclear if in vitro assays are predictive of functional immunity in humans, due to the lack of suitable animal models permissive for P. falciparum. A potentially useful solution described herein allows the antimalarial efficacy of human antibodies to be determined using rodent malaria parasites transgenic for P. falciparum antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured animals of an otherwise lethal malaria infection, and protection was crucially dependent on human FcgammaRI. This important finding documents the capacity of FcgammaRI to mediate potent antimalaria immunity and supports the development of FcgammaRI-directed therapy for human malaria.

  16. Human Serum Butyrylcholinesterase: A Bioscavenger for the Protection of Humans from Organophosphorus Exposure

    Science.gov (United States)

    2009-10-01

    enzymes. All animals exposed to GB vapor for 60 min showed signs of cardiac and neurological toxicity and died following exposure. Animals exposed to GB...min showed signs of cardiac and neurological toxicity and died following exposure. Animals exposed to GB vapor for 10 min also died, but showed signs...examined. The exogenous administration of AChE from fetal bovine serum and BChE from equine and human (Hu) serum, has been successfully used as a safe

  17. Protective Effects of Memantine on Hydroquinone-Treated Human Retinal Pigment Epithelium Cells and Human Retinal Müller Cells.

    Science.gov (United States)

    Moustafa, Mohamed Tarek; Ramirez, Claudio; Schneider, Kevin; Atilano, Shari R; Limb, Gloria Astrid; Kuppermann, Baruch D; Kenney, Maria Cristina

    2017-10-01

    Memantine (MEM) acts on the glutamatergic system by blocking N-methyl-d-aspartate (NMDA) glutamate receptors. The role that MEM plays in protecting retinal cells is unknown. Hydroquinone (HQ) is one of the cytotoxic components in cigarette smoke. In the present study, we tested whether pretreatment with MEM could protect against the cytotoxic effects of HQ on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) in vitro. Cells were plated, pretreated for 6 h with 30 μM of MEM, and then exposed for 24 h to 200, 100, 50, and 25 μM of HQ while MEM was still present. Cell viability (CV), reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and lactate dehydrogenase (LDH) release assays were performed. HQ-treated cells showed a dose-dependent decrease in CV and ΔΨm, but an increase in ROS production and LDH levels in both cell lines. MEM pretreatment reversed the CV in 50, 100, and 200 μM doses in ARPE-19 cells and at all HQ concentrations in MIO-M1 cells compared to HQ-treated cultures. ROS production was reversed in all HQ concentrations in both cell lines. ΔΨm was significantly increased after MEM pretreatment only in 50 μM HQ concentration for both cell lines. LDH levels were decreased at 50 and 25 μM HQ in ARPE-19 and MIO-M1 cells, respectively. HQ-induced toxicity is concentration dependent in ARPE-19 and MIO-M1 cultures. MEM exerts protective effects against HQ-induced toxicity on human retinal pigment epithelial and Müller cells in vitro.

  18. Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

    Directory of Open Access Journals (Sweden)

    Yan Ying

    2010-08-01

    Full Text Available Abstract Background Resveratrol (RES, a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood. Method The effects of RES on activation of unfolded protein responses (UPR were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS. Results Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK activation, activating transcription factor 6 (ATF6 splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP. Conclusions Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.

  19. CIRTification: Training in Human Research Protections for Community-Engaged Research Partners.

    Science.gov (United States)

    Anderson, Emily E

    2015-01-01

    Human research ethics training should provide relevant, meaningful information and build skills. Compliance should not be the only goal; training should also enhance knowledge, skills, and capacity. However, most currently available human research ethics training programs are geared toward learners who already have some research experience and working knowledge of research methods (e.g., graduate students, junior researchers); many community partners, however, have little or no prior exposure to research. More important, standard training programs do not adequately address the unique context of community-engaged research (CEnR). This article describes the development process, final curricular materials, and suggestions for successful implementation of CIRTification, a human research ethics training program designed specifically for community research partners who will be working on the "frontlines" of research. Development of CIRTification involved an extensive literature review, consultation with stakeholders including community partners, academic researchers, and human research protection program personnel. The curriculum, as well as information and materials to help potential users promote acceptance of the curriculum by their local institutional review boards (IRBs), are freely available online at www.go.uic.edu/CIRT. Ideally, community research partners who complete CIRTification will not only learn about the importance of protecting research participants but also be empowered to substantially contribute to the ethical practices of their respective research collaborations.

  20. Isoflurane Protects Against Human Endothelial Cell Apoptosis by Inducing Sphingosine Kinase-1 via ERK MAPK

    Directory of Open Access Journals (Sweden)

    H. Thomas Lee

    2012-01-01

    Full Text Available Endothelial dysfunction is a major clinical problem affecting virtually every patient requiring critical care. Volatile anesthetics are frequently used during the perioperative period and protect the heart and kidney against ischemia and reperfusion injury. We aimed to determine whether isoflurane, the most commonly used volatile anesthetic in the USA, protects against endothelial apoptosis and necrosis and the mechanisms involved in this protection. Human endothelial EA.hy926 cells were pretreated with isoflurane or carrier gas (95% room air + 5% CO2 then subjected to apoptosis with tumor necrosis factor-α or to necrosis with hydrogen peroxide. DNA laddering and in situ Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick-End Labeling (TUNEL staining determined EA.hy926 cell apoptosis and percent LDH released determined necrosis. We also determined whether isoflurane modulates the expression and activity of sphingosine kinase-1 (SK1 and induces the phosphorylation of extracellular signal regulated kinase (ERK MAPK as both enzymes are known to protect against cell death. Isoflurane pretreatment significantly decreased apoptosis in EA.hy926 cells as evidenced by reduced TUNEL staining and DNA laddering without affecting necrosis. Mechanistically, isoflurane induces the phosphorylation of ERK MAPK and increased SK1 expression and activity in EA.hy926 cells. Finally, selective blockade of SK1 (with SKI-II or S1P1 receptor (with W146 abolished the anti-apoptotic effects of isoflurane. Taken together, we demonstrate that isoflurane, in addition to its potent analgesic and anesthetic properties, protects against endothelial apoptosis most likely via SK1 and ERK MAPK activation. Our findings have significant clinical implication for protection of endothelial cells during the perioperative period and patients requiring critical care.

  1. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    Science.gov (United States)

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation.

  2. Protected areas as biodiversity benchmarks for human impact: agriculture and the Serengeti avifauna.

    Science.gov (United States)

    Sinclair, A R E; Mduma, Simon A R; Arcese, Peter

    2002-12-07

    Protected areas as biodiversity benchmarks allow a separation of the direct effects of human impact on biodiversity loss from those of other environmental changes. We illustrate the use of ecological baselines with a case from the Serengeti ecosystem, Tanzania. We document a substantial but previously unnoted loss of bird diversity in agriculture detected by reference to the immediately adjacent native vegetation in Serengeti. The abundance of species found in agriculture was only 28% of that for the same species in native savannah. Insectivorous species feeding in the grass layer or in trees were the most reduced. Some 50% of both insectivorous and granivorous species were not recorded in agriculture, with ground-feeding and tree species most affected. Grass-layer insect abundance and diversity was much reduced in agriculture, consistent with the loss of insectivorous birds. These results indicate that many species of birds will become confined to protected areas over time. We need to determine whether existing protected areas are sufficiently large to maintain viable populations of insectivorous birds likely to become confined to them. This study highlights the essential nature of baseline areas for assessing causes of change in human-dominated systems and for developing innovative strategies to restore biodiversity.

  3. Scutellaria radix Extract as a Natural UV Protectant for Human Skin.

    Science.gov (United States)

    Seok, Jin Kyung; Kwak, Jun Yup; Choi, Go Woon; An, Sang Mi; Kwak, Jae-Hoon; Seo, Hyeong-Ho; Suh, Hwa-Jin; Boo, Yong Chool

    2016-03-01

    Ultraviolet (UV) radiation induces oxidative injury and inflammation in human skin. Scutellaria radix (SR, the root of Scutellaria baicalensis Georgi) contains flavonoids with high UV absorptivity and antioxidant properties. The purpose of this study was to examine the potential use of SR extract as an additive in cosmetic products for UV protection. SR extract and its butanol (BuOH) fraction strongly absorbed UV radiation and displayed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radials and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals. They also attenuated the UV-induced death of HaCaT cells. Sunscreen creams, with or without supplementation of SR extract BuOH fraction, were tested in vivo in human trials to evaluate potential skin irritation and determine the sun protection factor (SPF). Both sunscreen creams induced no skin irritation. A sunscreen cream containing 24% ZnO showed an SPF value of 17.8, and it increased to 22.7 when supplemented with 5% SR extract BuOH fraction. This study suggests that SR-derived materials are useful as safe cosmetic additives that provide UV protection. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Human Milk Feeding as a Protective Factor for Retinopathy of Prematurity: A Meta-analysis.

    Science.gov (United States)

    Zhou, Jianguo; Shukla, Vivek V; John, Denny; Chen, Chao

    2015-12-01

    Studies have suggested that human milk feeding decreases the incidence of retinopathy of prematurity (ROP); however, conflicting results have been reported. The aim of this meta-analysis was to pool currently available data on incidence of ROP in infants fed human milk versus formula. Medline, PubMed, and EBSCO were searched for articles published through February 2015. Longitudinal studies comparing the incidence of ROP in infants who were fed human milk and formula were selected. Studies involving donor milk were not included. Two independent reviewers conducted the searches and extracted data. Meta-analysis used odds ratios (ORs), and subgroup analyses were performed. Five studies with 2208 preterm infants were included. Searches including various proportions of human milk versus formula, any-stage ROP, and severe ROP were defined to pool data for analyses. For any-stage ROP, the ORs (95% confidence intervals [CIs]) were as follows: exclusive human milk versus any formula, 0.29 (0.12 to 0.72); mainly human milk versus mainly formula, 0.51 (0.26 to 1.03); any human milk versus exclusive formula, 0.54 (0.15 to 1.96); and exclusive human milk versus exclusive formula, 0.25 (0.13 to 0.49). For severe ROP, they were 0.11 (0.04 to 0.30), 0.16 (0.06 to 0.43), 0.42 (0.08 to 2.18), and 0.10 (0.04 to 0.29), respectively. Prospective randomized studies being impossible because of ethical issues, we chose observational studies for analysis. A few studies involving subgroup analyses presented high heterogeneity. Based on current limited evidence, in very preterm newborns, human milk feeding potentially plays a protective role in preventing any-stage ROP and severe ROP. Copyright © 2015 by the American Academy of Pediatrics.

  5. Formation of a protection film on the human skin by microparticles

    Science.gov (United States)

    Lademann, J.; Schanzer, S.; Richter, H.; Antoniou, C.; Knorr, F.; Sterry, W.; Patzelt, A.

    2008-09-01

    Laser scanning microscopy and tape stripping, in combination with optical methods, were used to analyze the distribution and penetration of a barrier cream into the horny layer (stratum corneum) of the human skin under in vivo conditions. The barrier cream contained microparticles of 10 - 100 μm loaded with antioxidant substances. The cream was designed for protection of the skin surface against the destructive action of free radicals, produced by systemically applied chemotherapeutic agents reaching the skin surface via the sweat. Both methods were able to demonstrate that the barrier cream was distributed homogeneously on the skin surface forming a protection film. A penetration into deeper parts of the stratum corneum (SC) was not observed.

  6. NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

    Directory of Open Access Journals (Sweden)

    Anselmo Jiro Kamada

    2014-11-01

    Full Text Available Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1 infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL-1 family (IL-1, IL-18 and IL-33 members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls. NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37. rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

  7. Protective effect of hawthorn extract against genotoxicity induced by methyl methanesulfonate in human lymphocytes.

    Science.gov (United States)

    Hosseinimehr, Seyed Jalal; Azadbakht, Mohammad; Tanha, Mohammad; Mahmodzadeh, Aziz; Mohammadifar, Sohila

    2011-05-01

    The preventive effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by methyl methanesulfonate (MMS) has been investigated in human cultured blood lymphocytes. Peripheral blood samples were collected from human volunteers at 0 (10 minutes before), and at 1 and 2 hours after a single oral ingestion of 1 g hawthorn powder extract. At each time point, the whole blood was treated in vitro with MMS (200 µmol) at 24 hours after cell culture, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. The lymphocytes treated with hawthorn and MMS to exhibit a significant decreasing in the incidence of micronucleated binucleated cells, as compared with similarly MMS-treated lymphocytes from blood samples collected at 0 hour. The maximum protection and decreasing in frequency of micronuclei (36%) was observed at 1 hour after ingestion of hawthorn extract. The high performance liquid chromatography (HPLC) analysis showed that hawthorn contained chlorogenic acid, epicatechin and hyperoside. It is obvious that hawthorn, particularly flavonoids constituents with antioxidative activity, reduced the oxidative stress and genotoxicity induced by toxic compounds. This set of data may have an important application for the protection of human lymphocyte from the genetic damage and side effects induced by chemicals hazardous in people.

  8. Contribution of the police negotiating team to the protection of human rights in specific security situations

    Directory of Open Access Journals (Sweden)

    Subošić Dane

    2012-01-01

    Full Text Available Legal right of police to use force, especially firearms, makes modern police mission seem inconsistent: in order to protect the rights of one, the police must limit the rights of others, which raises the question of optimal measures between these opposites. The most dangerous is the police action which encroaches on the right to life, thus indirectly interfering in other human rights. This applies equally to both citizens and the offenders. In an effort to minimize the possibility of eroding the right to life, the modern police forces have developed mechanisms of so-called police negotiating. Respecting the principles of legality, humanity and expertise, members of the of specialized police units engage in negotiations with the most dangerous criminals in order to prevent them in further criminal intent on one hand and in order to solve the crisis without the use of police force, on the other. In addition a notable involvement of police negotiators in prevention of suicide attempts has been observed. In this regard, the paper explores the contribution of the negotiating team of the Ministry of Internal Affairs of the Republic of Serbia to the protection of human rights in Serbia in the period 2005. - 2010.

  9. Reporting of ethical protection in recent oral and maxillofacial surgery research involving human subjects.

    Science.gov (United States)

    Pitak-Arnnop, P; Sader, R; Hervé, C; Dhanuthai, K; Bertrand, J-Ch; Hemprich, A

    2009-07-01

    This retrospective observational study investigated the frequency of reporting ethical approval and informed consent in recently published oral and maxillofacial surgery (OMS) research involving human subjects. All research involving human subjects published in the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, British Journal of Oral and Maxillofacial Surgery, and Journal of Cranio-Maxillofacial Surgery during January to June 2005-2007 were analysed for disclosure of ethical approval by a local ethical committee and obtaining informed consent from the subjects. 534 articles were identified; ethical approval was documented in 118 (22%) and individual patient consent in 135 (25%). 355 reports (67%) did not include a statement on ethical approval or informed consent and only 74 reports (14%) disclosed statements of both. Ethical documentation in retrospective and observational studies was scant; 12% of randomised controlled trials and 38% of non-random trials did not report both of ethical protections. Most recent OMS publications involving humans failed to mention ethical review or subjects' consent. Authors must adhere to the international research ethics guidelines and journal instructions, while editors should play a gatekeeper role to protect research participants, uphold scientific integrity and maintain public trust in the experimental process and OMS profession.

  10. A closed-loop stepper motor waist-pull system for inducing protective stepping in humans.

    Science.gov (United States)

    Pidcoe, P E; Rogers, M W

    1998-04-01

    Past approaches for inducing protective stepping to preserve standing balance in humans have either lacked the flexibility of control over the initial conditions of falling, or involved considerable mass which limits mobility of the system. This report describes the design and function of a stepper motor closed-loop waist-pull system for evoking protective stepping responses. Bench testing with applied load-motion profile combinations indicated performance degradation for force levels greater than 204 N which was well within the levels encountered in human experiments. An optical encoder feedback design allowed a positional accuracy of 0.00225 mm per step. A regression analysis of specified versus recorded velocities resulted in an acceptable fit (r2 = 0.99). The mean rise time was 63.0+/-18.0 (SD) ms and was consistent up to the load limits of the device. In human experiments repeated perturbations were consistently realized. Applied motion profiles were generally comparable at the pelvic level for subjects of different geometry, weight, and inertia despite a tendency for slight positional lag. The method allows flexible and accurate control of the initial conditions of a perturbation-induced fall to elicit steps. The system dimensions and moveability allow it to be implemented into clinical environments.

  11. Dynamic simulation and finite element analysis of the human mandible injury protected by polyvinyl alcohol sponge

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, Alireza; Navidbakhsh, Mahdi, E-mail: mnavid@iust.ac.ir; Razaghi, Reza

    2014-09-01

    There have been intensive efforts to find a suitable kinetic energy absorbing material for helmet and bulletproof vest design. Polyvinyl alcohol (PVA) sponge is currently in extensive use as scaffolding material for tissue engineering applications. PVA can also be employed instead of commonly use kinetic energy absorbing materials to increase the kinetic energy absorption capacity of current helmet and bulletproof vest materials owing to its excellent mechanical properties. In this study, a combined hexahedral finite element (FE) model is established to determine the potential protection ability of PVA sponge in controlling the level of injury for gunshot wounds to the human mandible. Digital computed tomography data for the human mandible are used to establish a three-dimensional FE model of the human mandible. The mechanism by which a gunshot injures the protected mandible by PVA sponge is dynamically simulated using the LS-DYNA code under two different shot angles. The stress distributions in different parts of the mandible and sponge after injury are also simulated. The modeling results regardless of shot angle reveal that the substantial amount of kinetic energy of the steel ball (67%) is absorbed by the PVA sponge and, consequently, injury severity of the mandible is significantly decreased. The highest energy loss (170 J) is observed for the impact at entry angle of 70°. The results suggest the application of the PVA sponge as an alternative reinforcement material in helmet and bulletproof vest design to absorb most of the impact energy and reduce the transmitted load. - Highlights: • The ability of PVA sponge to control the injury to the human mandible is computed. • A hexahedral FE model for gunshot wounds to the human mandible is established. • The kinetic energy and injury severity of the mandible is minimized by the sponge. • The highest energy loss (170 J) is observed for the impact at entry angle of 70°. • PVA suggests as an alternative

  12. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

    Science.gov (United States)

    Mordmüller, Benjamin; Surat, Güzin; Lagler, Heimo; Chakravarty, Sumana; Ishizuka, Andrew S; Lalremruata, Albert; Gmeiner, Markus; Campo, Joseph J; Esen, Meral; Ruben, Adam J; Held, Jana; Calle, Carlos Lamsfus; Mengue, Juliana B; Gebru, Tamirat; Ibáñez, Javier; Sulyok, Mihály; James, Eric R; Billingsley, Peter F; Natasha, K C; Manoj, Anita; Murshedkar, Tooba; Gunasekera, Anusha; Eappen, Abraham G; Li, Tao; Stafford, Richard E; Li, Minglin; Felgner, Phil L; Seder, Robert A; Richie, Thomas L; Sim, B Kim Lee; Hoffman, Stephen L; Kremsner, Peter G

    2017-02-23

    A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 10(4) PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 10(3) (group I) or 1.28 × 10(4) (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 10(4) PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

  13. Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats

    Science.gov (United States)

    Jin, Luyuan; Qin, Lizheng; Xia, Dengsheng; Liu, Xibao; Fan, Zhipeng; Zhang, Chunmei; Gu, Liankun; He, Junqi; Ambudkar, Indu S.; Deng, Dajun; Wang, Songlin

    2014-01-01

    Up to 25% of the circulating nitrate in blood is actively taken up, concentrated, and secreted into saliva by the salivary glands. Salivary nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity or stomach and then further converted to nitric oxide (NO) in vivo, which may play a role in gastric protection. However, whether salivary nitrate is actively secreted in human beings has not yet been determined. This study was designed to determine whether salivary nitrate is actively secreted in human beings as an acute stress response and what role salivary nitrate plays in stress-induced gastric injury. To observe salivary nitrate function under stress conditions, alteration of salivary nitrate and nitrite was analyzed among 22 healthy volunteers before and after a strong stress activity, jumping down from a platform at the height of 68m. A series of stress indexes was analyzed to monitor the stress situation. We found that both the concentration and the total amount of nitrate in mixed saliva were significantly increased in the human volunteers immediately after the jump, with an additional increase 1 h later (p salivary nitrate and nitrite in stress protection, we further carried out a water-immersion-restraint stress (WIRS) assay in male adult rats with bilateral parotid and submandibular duct ligature (BPSDL). Intragastric nitrate, nitrite, and NO; gastric mucosal blood flow; and gastric ulcer index (UI) were monitored and nitrate was administrated in drinking water to compensate for nitrate secretion in BPSDL animals. Significantly decreased levels of intragastric nitrate, nitrite, and NO and gastricmucosal blood flow were measured in BPSDL rats during the WIRS assay compared to sham control rats (p salivary nitrate secretion and nitrite formation, which may play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway. PMID:23277147

  14. Special procedural measures and the protection of human rights
    General report

    Directory of Open Access Journals (Sweden)

    John A.E. Vervaele

    2009-10-01

    Full Text Available The aim of the general report is to conduct a comparative analysis of the national reports in order to trace transformation processes in domestic criminal justice systems, in particular criminal process, as special procedural measures are introduced to deal with terrorism and organised crime, and to map whether this has led countries to depart from their own fundamental rules, procedures, principles and applicable human rights standards. Starting from the premise that the integrated system of criminal law has three dimensions – the protection of individuals (the shield dimension, the provision of instruments of law enforcement (the sword dimension, and of checks and balances/trias politica (the constitutional dimension – the report provides a comprehensive overview of interrelated transformations, mostly in the pre-trial setting, that have affected all three in three waves of ‘war’ (on drugs, organised crime and terrorism. In many countries, procedural guarantees and principles that protect against the infringement of fair trial rights are considered a burden to the efficiency of serious crime enforcement. These reforms have resulted in a clear expansion of the punitive state and a blurring of classic distinctions, and do not favour the rule of law. The focus on public security and preventive coercive investigation undermines the criminal justice system. With the criminal justice system increasingly used as an instrument to regulate the present and/or the future rather than to punish past behaviour, and a criminal process in which pre-trial investigation is not about truth-finding related to committed crime, but about the construction and de-construction of social dangerousness, the interests of national security may be said to be prevailing over justice and to be threatening due process and the protection of human rights – notwithstanding that general principles of criminal procedure seem to have become more important in the reporting

  15. Towards modelling flood protection investment as a coupled human and natural system

    Science.gov (United States)

    O'Connell, P. E.; O'Donnell, G.

    2014-01-01

    Due to a number of recent high-profile flood events and the apparent threat from global warming, governments and their agencies are under pressure to make proactive investments to protect people living in floodplains. However, adopting a proactive approach as a universal strategy is not affordable. It has been argued that delaying expensive and essentially irreversible capital decisions could be a prudent strategy in situations with high future uncertainty. This paper firstly uses Monte Carlo simulation to explore the performance of proactive and reactive investment strategies using a rational cost-benefit approach in a natural system with varying levels of persistence/interannual variability in annual maximum floods. It is found that, as persistence increases, there is a change in investment strategy optimality from proactive to reactive. This could have implications for investment strategies under the increasingly variable climate that is expected with global warming. As part of the emerging holistic approaches to flood risk management, there is increasing emphasis on stakeholder participation in determining where and when flood protection investments are made, and so flood risk management is becoming more people-centred. As a consequence, multiple actors are involved in the decision-making process, and the social sciences are assuming an increasingly important role in flood risk management. There is a need for modelling approaches which can couple the natural and human system elements. It is proposed that coupled human and natural system (CHANS) modelling could play an important role in understanding the motivations, actions and influence of citizens and institutions and how these impact on the effective delivery of flood protection investment. A framework for using agent-based modelling of human activities leading to flood investments is outlined, and some of the challenges associated with implementation are discussed.

  16. How Does Iranian's Legal System Protect Human Vulnerability and Personal Integrity in Medical Research?

    Science.gov (United States)

    Karoubi, Mohammad Taghi; Akhondi, Mohammad Mehdi

    2011-04-01

    The astonishing advance of medical science in recent decades has had endless advantages for humans, including improved level of health, prevention of disease and advances in treatment. These advances depend to a great extent on conducting continuous research. However, besides its enormous advantages, the sole interest of medical science undermines the principles of respect for human vulnerability and personal integrity, in both positive and negative approaches. The positive approach refers to the people who participate in research and practice, while the negative approach refers to people who are deprived of research and practice. The authors of this work, based on legal or moral grounds try to analyse the tension between the principle of respect for human vulnerability and personal integrity and the interest of medical science. Undoubtedly, in applying scientific knowledge and medical practice human vulnerability should be taken into account. In this regard, especially vulnerable individuals and groups should be protected and the personal integrity of such individuals respected. In the light of the merits of Islamic law, this paper is designed to examine the significance of the principles of human vulnerability and personal integrity in medical research by studying the international documents as formalised by UNESCO in order to explore the place of these principles in the Iranian legal system.

  17. Numerical prediction of degree of skin burn in thermal protective garment-air gap-human body system

    National Research Council Canada - National Science Library

    Tian Ming-Wei; Zhend Wang; Lin Wang; Qu Li-Jun; Chen Shao-Juan; Zhu Shi-Feng; Yu Rong-Rong; Zhao Ren-Hai; Zhao Hong-Tao

    2017-01-01

    .... The coupling model of thermal protective garment, air-gap, and human body has been widely established, but the heat transfer in air-gap was commonly simplified, resulting in inaccurate results...

  18. Are research subjects adequately protected? A review and discussion of studies conducted by the Advisory Committee on Human Radiation Experiments.

    Science.gov (United States)

    Kass, Nancy E; Sugarman, Jeremy

    1996-09-01

    In light of information uncovered about human radiation experiments conducted during the Cold War, an important charge for the Advisory Committee on Human Radiation Experiments was to assess the current state of protections for human research subjects. This assessment was designed to enhance the Committee's ability to make informed recommendations for the improvement of future policies and practices for the protection of research subjects. The Committee's examination of current protections revealed great improvement over those from the past, yet some problems remain. Although the data collected by the Committee highlight specific areas in need of attention, the Committee's work should be viewed in part as the beginning of a series of ongoing assessments of the adequacy and effectiveness of the protections afforded to human subjects.

  19. The latest progress in human rights protection of LGBTI community in the Inter-American field

    OpenAIRE

    Negro Alvarado, Dante Mauricio

    2014-01-01

    The text describes the main progress in depicting the LGBTI topic in the Inter-American area. It begins with the analysis of some conceptual issues that are crossed to the topic and discuss the importance of including political commitments and statements in the resolutions adopted by the General Assembly of OAS (Organization of American States) related to the LGTBI community protection. Even though, a few cases have gone to the Inter-American Commission on Human Rights, some landmark cases ha...

  20. PROTECTING EGG DONORS AND HUMAN EMBRYOS-THE FAILURE OF THE SOUTH KOREAN BIOETHICS AND BIOSAFETY ACT

    National Research Council Canada - National Science Library

    Mukta Jhalani

    2008-01-01

    ... Korea passed the Bioethics and Biosafety Act to regulate biotechnology research. In its current form, the Bioethics and Biosafety Act fails to adequately protect egg donors and human embryos. The Bioethics and Biosafety Act does not have adequate safeguards to protect egg donors, such as a requirement of voluntary consent and a requirement tha...

  1. Privacy as human flourishing: could a shift towards virtue ethics strengthen privacy protection in the age of Big Data?

    NARCIS (Netherlands)

    van der Sloot, B.

    2014-01-01

    Privacy is commonly seen as an instrumental value in relation to negative freedom, human dignity and personal autonomy. Article 8 ECHR, protecting the right to privacy, was originally coined as a doctrine protecting the negative freedom of citizens in vertical relations, that is between citizen and

  2. Human papillomavirus vaccines and the potential for cross-protection between related HPV types.

    Science.gov (United States)

    Ault, Kevin A

    2007-11-01

    The majority of human papillomavirus (HPV) belong to the genus alpha-papillomavirus, which can be further subdivided into species and then strains. Approximately 200 strains of HPV have been identified, and the whole genomes of approximately 100 strains have been (discovered) and completely sequenced. Between 13 and 18 HPV strains have been characterized as conferring a high oncogenic risk, with 12 of these strains belonging to the HPV species 7 (HPV-18, -39, -45, -59, -68) and species 9 (HPV-16, -31, -33, -35, -52, -58, -67). While strains belonging to the same species are phylogenetically related, they may differ biologically. The available data on whether natural HPV infection infers cross protection against other related strains from the same species are equivocal. There are data to indicate that following HPV infection, there appears to be a reduced risk of contracting the same strain of HPV. However, there is also evidence to indicate that natural infection with HPV does not confer group-specific immune protection or general protection from reinfection with genital HPV mucosal types. Recent studies conducted with HPV vaccines show data on cross-protection against related HPV strains. In vitro experiments with serum from recipients of the quadrivalent HPV vaccine (HPV-6/8/16/18) show neutralization of HPV 45 pseudovirions. Cross-protection following vaccination of women (n=776) with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that, over a period of up to 4.5 years, long-term vaccine efficacy was observed for HPV-16 and -18, and vaccine efficacy was also observed against incident infection with HPV-31 and -45. These findings are supported by the results of a large study (n=18,644) in women aged 15 to 25 years vaccinated with the adjuvant bivalent HPV vaccine (HPV-16/18). Over a period of 6 months, cross-protection was observed against persistent infections with HPV-45, -31 and -52, and at 12 months, modest protection was demonstrated against

  3. Radiation Protection of Environment under the Light of the New Concept of Radiation Protection of Non-Human Species

    Energy Technology Data Exchange (ETDEWEB)

    Hansruedi Voelkle [Swiss Federal Office of Public Health, Environmental Radioactivity Section, c/o Physics Department, University of Fribourg Chemin du Musee 3, 1700 Fribourg (Switzerland)

    2006-07-01

    The purpose of this presentation is to discuss the question of whether radiation protection should be extended to plants and animals. Until now the recommendations of ICRP have been focused exclusively on the protection of man from ionizing radiation. It was assumed that, if man is protected, the quality of the living environment is not impaired. In recent years adequate principles, recommendations and laws have become necessary in order to protect the environment from man made toxins. These recommendations aimed to conserve plants and animals, to maintain the diversity of species, the health and status of natural habitats and the natural resources of our planet, to warrant natural evolution and selection processes in order to transmit a healthy world to future generations. Reflections have been made as to whether particular protection of fauna and flora from ionizing radiation should be included. This article presents some considerations from the point of view of operational radiation protection and some comments to the work already done by ICRP committee 5. The final purpose is to invite the audience to make its own reflections and to communicate any criticisms, comments or suggestions to committee 5 of ICRP. (author)

  4. Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure.

    Science.gov (United States)

    Li, Ning; Hansen, Brian J; Csepe, Thomas A; Zhao, Jichao; Ignozzi, Anthony J; Sul, Lidiya V; Zakharkin, Stanislav O; Kalyanasundaram, Anuradha; Davis, Jonathan P; Biesiadecki, Brandon J; Kilic, Ahmet; Janssen, Paul M L; Mohler, Peter J; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

    2017-07-26

    The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN's ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation. Hence, to innovate the translational study of human SAN structural and functional robustness, we integrated intramural optical mapping, 3D histology reconstruction, and molecular mapping of the ex vivo human heart. When challenged with adenosine or atrial pacing, redundant intranodal pacemakers within the human SAN maintained automaticity and delivered electrical impulses to the atria through sinoatrial conduction pathways (SACPs), thereby ensuring a fail-safe mechanism for robust maintenance of sinus rhythm. During adenosine perturbation, the primary central SAN pacemaker was suppressed, whereas previously inactive superior or inferior intranodal pacemakers took over automaticity maintenance. Sinus rhythm was also rescued by activation of another SACP when the preferential SACP was suppressed, suggesting two independent fail-safe mechanisms for automaticity and conduction. The fail-safe mechanism in response to adenosine challenge is orchestrated by heterogeneous differences in adenosine A1 receptors and downstream GIRK4 channel protein expressions across the SAN complex. Only failure of all pacemakers and/or SACPs resulted in SAN arrest or conduction block. Our results unmasked reserve mechanisms that protect the human SAN pacemaker and conduction complex from rhythm failure, which may contribute to treatment of SAN arrhythmias. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing.

    Science.gov (United States)

    Kim, Jung-Hyun; Ebersole, Thomas; Kouprina, Natalay; Noskov, Vladimir N; Ohzeki, Jun-Ichirou; Masumoto, Hiroshi; Mravinac, Brankica; Sullivan, Beth A; Pavlicek, Adam; Dovat, Sinisa; Pack, Svetlana D; Kwon, Yoo-Wook; Flanagan, Patrick T; Loukinov, Dmitri; Lobanenkov, Victor; Larionov, Vladimir

    2009-04-01

    The role of repetitive DNA sequences in pericentromeric regions with respect to kinetochore/heterochromatin structure and function is poorly understood. Here, we use a mouse erythroleukemia cell (MEL) system for studying how repetitive DNA assumes or is assembled into different chromatin structures. We show that human gamma-satellite DNA arrays allow a transcriptionally permissive chromatin conformation in an adjacent transgene and efficiently protect it from epigenetic silencing. These arrays contain CTCF and Ikaros binding sites. In MEL cells, this gamma-satellite DNA activity depends on binding of Ikaros proteins involved in differentiation along the hematopoietic pathway. Given our discovery of gamma-satellite DNA in pericentromeric regions of most human chromosomes and a dynamic chromatin state of gamma-satellite arrays in their natural location, we suggest that gamma-satellite DNA represents a unique region of the functional centromere with a possible role in preventing heterochromatin spreading beyond the pericentromeric region.

  6. Isorhamnetin Protects Human Keratinocytes against Ultraviolet B-Induced Cell Damage

    Science.gov (United States)

    Han, Xia; Piao, Mei Jing; Kim, Ki Cheon; Madduma Hewage, Susara Ruwan Kumara; Yoo, Eun Sook; Koh, Young Sang; Kang, Hee Kyoung; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Chae, Sungwook; Hyun, Jin Won

    2015-01-01

    Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death. PMID:26157553

  7. Research in the hospital setting on human subjects. Protecting the patient and the institution.

    Science.gov (United States)

    Scheuer, R

    1993-10-01

    A hospital's institutional review board is charged with the responsibility of fully protecting the rights of research subjects. In doing so, the board establishes that research protocols are based on sound scientific principles, that benefits to research subjects outweigh the risks, and that the subject's consent is informed and not coerced. Although it has been argued that risk management has no role in the activities of such boards, the literature indicates that risk management and quality assurance principles apply to all areas of the institution, including the activities of the board. The institution must ensure that its researchers and board members are as fully protected as possible from civil and criminal liability and that the integrity of those conducting the research is established and maintained. The institution must also provide sufficient support for the board to conduct its reviews and educate the research community and board members on current and evolving laws and regulations governing human research. Risk prevention and quality assurance strategies should recognize the rights of the research subject as paramount while protecting the institution, its researchers, and the community served.

  8. DPP-4 inhibition protects human umbilical vein endothelial cells from hypoxia-induced vascular barrier impairment

    Directory of Open Access Journals (Sweden)

    Naoko Hashimoto

    2017-09-01

    Full Text Available Dipeptidyl peptidase-4 (DPP-4 inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor. Immunocytochemistry of vascular endothelial (VE- cadherin showed that jagged VE-cadherin staining pattern induced by hypoxia was restored by treatment with Diprotin A. The increased level of cleaved β-catenin in response to hypoxia was significantly attenuated by Diprotin A, suggesting that DPP-4 inhibition protects endothelial adherens junctions from hypoxia. Subsequently, we found that Diprotin A inhibited hypoxia-induced translocation of NF-κB from cytoplasm to nucleus through decreasing TNF-α expression level. Furthermore, the tube formation assay showed that Diprotin A significantly restored hypoxia-induced decrease in number of tubes by HUVECs. These results suggest that DPP-4 inhibitior protects HUVECs from hypoxia-induced barrier impairment.

  9. Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes

    Science.gov (United States)

    LIN, FUQUAN; XU, WEN; GUAN, CUIPING; ZHOU, MIAONI; HONG, WEISONG; FU, LIFANG; LIU, DONGYIN; XU, AIE

    2012-01-01

    Niacin and its related derivatives have been shown to have effects on cellular activities. However, the molecular mechanism of its reduced immunosuppressive effects and photoprotective effects remains unclear. In this study, we investigated the molecular mechanism of the photoprotective effect of niacin in ultraviolet (UV)-irradiated human skin keratinocytes (HaCaT cells). We found that niacin effectively suppressed the UV-induced cell death and cell apoptosis of HaCaT cells. Existing data have shown that AKT activation is involved in the cell survival process. Yet, the potential mechanism of niacin in protection against UV-induced skin damage has thus far not fully been eluvidated. We observed that niacin pretreatment enhances UV induced activation of AKT (Ser473 phosphorylation) as well as that of the downstream signal mTOR (S6 and 4E-BP1 phosphorylation). The PI3K/AKT inhibitor, LY294002, and the mTOR inhibitor, rapamycin, largely neutralized the protective effects of niacin, suggesting that AKT and downstream signaling mTOR/S6 activation are necessary for the niacin-induced protective effects against UV-induced cell death and cell apoptosis. Collectively, our data suggest that niacin may be utilized to prevent UV-induced skin damage and provide a novel mechanism of its photoprotective effects against the UV radiation of sunlight by modulating both AKT and downstream mTOR signaling pathways. PMID:22246168

  10. Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells.

    Science.gov (United States)

    Patwardhan, Juilee; Bhatt, Purvi

    2015-10-01

    The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells. Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway. FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10-40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection. Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a

  11. Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Eduardo Villamor-Martínez

    2018-02-01

    Full Text Available Bronchopulmonary dysplasia (BPD is the most common complication after preterm birth. Pasteurized donor human milk (DHM has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF if the mother’s own milk (MOM is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR 0.89, 95% confidence interval (CI 0.60–1.32. However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90. An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68–0.95. Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62–0.96. In conclusion, our data suggest that DHM protects against BPD in very preterm infants.

  12. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Brunetto de Farias, Caroline [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Children' s Cancer Institute, 90420-140 Porto Alegre, RS (Brazil); Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Heinen, Tiago Elias; Pereira dos Santos, Rafael [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Abujamra, Ana Lucia [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Children' s Cancer Institute, 90420-140 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Schwartsmann, Gilberto [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); and others

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer BDNF protected HT-29 colorectal cancer cells from the antitumor effect of cetuximab. Black-Right-Pointing-Pointer TrkB inhibition potentiated the antitumor effect of cetuximab. Black-Right-Pointing-Pointer BDNF/TrkB signaling might be involved in resistance to anti-EGFR therapy. -- Abstract: The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling can protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.

  13. Human Milk Oligosaccharides Protect Bladder Epithelial Cells Against Uropathogenic Escherichia coli Invasion and Cytotoxicity

    Science.gov (United States)

    Lin, Ann E.; Autran, Chloe A.; Espanola, Sophia D.; Bode, Lars; Nizet, Victor

    2014-01-01

    The invasive pathogen uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). Recurrent infection that can progress to life-threatening renal failure has remained as a serious global health concern in infants. UPEC adheres to and invades bladder epithelial cells to establish infection. Studies have detected the presence of human milk oligosaccharides (HMOs) in urine of breast-fed, but not formula-fed, neonates. We investigated the mechanisms HMOs deploy to elicit protection in human bladder epithelial cells infected with UPEC CFT073, a prototypic urosepsis-associated strain. We found a significant reduction in UPEC internalization into HMO-pretreated epithelial cells without observing any significant effect in UPEC binding to these cells. This event coincides with a rapid decrease in host cell cytotoxicity, recognized by LIVE/DEAD staining and cell detachment, but independent of caspase-mediated or mitochondrial-mediated programmed cell death pathways. Further investigation revealed HMOs, and particularly the sialic acid-containing fraction, reduced UPEC-mediated MAPK and NF-κB activation. Collectively, our results indicate that HMOs can protect bladder epithelial cells from deleterious cytotoxic and proinflammatory effects of UPEC infection, and may be one contributing mechanism underlying the epidemiological evidence of reduced UTI incidence in breast-fed infants. PMID:23990566

  14. Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

    Science.gov (United States)

    Bayer, Avraham; Lennemann, Nicholas J; Ouyang, Yingshi; Bramley, John C; Morosky, Stefanie; Marques, Ernesto Torres De Azeved; Cherry, Sara; Sadovsky, Yoel; Coyne, Carolyn B

    2016-05-11

    During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [The protection effects of resveratrol on irradiated human pneumonic cell lines and its mechanism].

    Science.gov (United States)

    Fu, Xiao-yue; Xue, Jian-xin; Zhou, Lin; Wang, Yong-sheng; Huang, Mei-juan; Li, Lu; Lu, You

    2012-05-01

    This study was to explore whether resveratrol could protect human bronchial epithelial cells (HBE) and human fetal lung fibroblasts (MRC5) from radiation injury and to investigate its potential HBE and MRC5 were divided into four groups: Group 1 (Vehicle), control group, only mechanism. treated with vehicle; Group 2 (resveratrol, Res), the resveratrol group, treated with 5 micromol/L resveratrol; Group 3 (RT+Vehicle), the X-ray irradiation group, only subjected to irradiation of 20 Gy X-ray; Group 4 (RT+Res), the combination therapy group, 2 hours before X-ray treatment (20 Gy, 8. 33 Gy/min for 144 s), 5 micromol/L resveratrol was added to the cells. Several experimental methods were used to observe cellular morphology, ultrastructure, viability, DNA damage, apoptosis, and to determine the change of oxidative stress indexes such as reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) and superoxide dismutase (SOD). X-ray could induce HBE and MRC5 cell injury. Resveratrol could significantly ease the morphological and ultrastructure injury, relieve the decrease of cellular viability and the damage of DNA, and reduce cellular apoptosis. Besides, oxidative stress indexes including ROS, MDA, GSH, SOD were improved by resveratrol after irradiation. Resveratrol protect HBE and MRC5 from radiation injury, which is related to the alleviation of oxidative stress injury.

  16. Protecting human security: proposals for the G7 Ise-Shima Summit in Japan.

    Science.gov (United States)

    2016-05-21

    In today's highly globalised world, protecting human security is a core challenge for political leaders who are simultaneously dealing with terrorism, refugee and migration crises, disease epidemics, and climate change. Promoting universal health coverage (UHC) will help prevent another disease outbreak similar to the recent Ebola outbreak in west Africa, and create robust health systems, capable of withstanding future shocks. Robust health systems, in turn, are the prerequisites for achieving UHC. We propose three areas for global health action by the G7 countries at their meeting in Japan in May, 2016, to protect human security around the world: restructuring of the global health architecture so that it enables preparedness and responses to health emergencies; development of platforms to share best practices and harness shared learning about the resilience and sustainability of health systems; and strengthening of coordination and financing for research and development and system innovations for global health security. Rather than creating new funding or organisations, global leaders should reorganise current financing structures and institutions so that they work more effectively and efficiently. By making smart investments, countries will improve their capacity to monitor, track, review, and assess health system performance and accountability, and thereby be better prepared for future global health shocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Xue - Fang Chen

    2013-06-01

    Full Text Available AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05; caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05. In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract.

  18. Potent protection of gallic acid against DNA oxidation: Results of human and animal experiments

    Energy Technology Data Exchange (ETDEWEB)

    Ferk, Franziska; Chakraborty, Asima [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Jaeger, Walter [Department of Clinical Pharmacy and Diagnostic, University of Vienna, Vienna (Austria); Kundi, Michael [Institute of Environmental Health, Center for Public Health, Medical University of Vienna, A-1090 Vienna (Austria); Bichler, Julia; Misik, Miroslav [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Department of Nutritional Sciences, University of Vienna, 1090 Vienna (Austria); Grasl-Kraupp, Bettina; Sagmeister, Sandra [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Haidinger, Gerald [Department of Epidemiology, Center for Public Health, Medical University of Vienna, A-1090 Vienna (Austria); Hoelzl, Christine; Nersesyan, Armen [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Dusinska, Maria [Health Effect Laboratory, Center for Ecological Economics, Norwegian Institute for Air Research, NO-2027 Kjeller (Norway); Simic, Tatjana [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Knasmueller, Siegfried, E-mail: siegfried.knasmueller@meduniwien.ac.at [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria)

    2011-10-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a constituent of plant derived foods, beverages and herbal remedies. We investigated its DNA protective properties in a placebo controlled human intervention trial in single cell gel electrophoresis experiments. Supplementation of drinking water with GA (12.8 mg/person/d) for three days led to a significant reduction of DNA migration attributable to oxidised pyrimidines (endonuclease III sensitive sites) and oxidised purines (formamidopyrimidine glycosylase sensitive sites) in lymphocytes of healthy individuals by 75% and 64% respectively. Also DNA damage caused by treatment of the cells with reactive oxygen species (ROS) was reduced after GA consumption (by 41%). These effects were paralleled by an increase of the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathion-S-transferase-{pi}) and a decrease of intracellular ROS concentrations in lymphocytes, while no alterations of the total antioxidant capacity (TAC), of malondialdehyde levels in serum and of the urinary excretion of isoprostanes were found. Experiments with rats showed that GA reduces oxidatively damaged DNA in lymphocytes, liver, colon and lungs and protects these organs against {gamma}-irradiation-induced strand breaks and formation of oxidatively damaged DNA-bases. Furthermore, the number of radiation-induced preneoplastic hepatic foci was decreased by 43% after oral administration of the phenolic. Since we did not find alterations of the TAC in plasma and lipid peroxidation of cell membranes but intracellular effects it is likely that the antioxidant properties of GA seen in vivo are not due to direct scavenging of radicals but rather to indirect mechanisms (e.g. protection against ROS via activation of transcription factors). As the amount of GA used in the intervention trial is similar to the daily intake in Middle Europe (18 mg/person/day), our findings indicate that it may contribute to prevention of

  19. Skin Protective Effects of Nannochloropsis gaditana Extract on H2O2-Stressed Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Sophia Letsiou

    2017-07-01

    Full Text Available Nowadays, there is huge interest in natural products obtained from marine organisms that can promote a state of health and well-being for humans. Microalgae represent a primary source of bioactive compounds that could be used as functional ingredients in cosmetic formulations. The aim of the present study is to evaluate, for the first time, the effects of Nannochloropsis gaditana extract against oxidative stress in human primary fibroblasts so as to investigate the potential applications of it in cosmetics. To gain an insight into the molecular mechanisms of N. gaditana bioactivity, we developed a new RT-qPCR platform for studying transcript accumulation for an array of selected genes (up to 100 involved in many skin-related processes including anti-aging, hydration, oxidative stress response, and DNA damage. For the oxidative stress evaluation, H2O2 was used as a stressor. The study of the transcript accumulation of genes revealed that N. gaditana extract exhibits skin protection properties by mediating oxidative responses and apoptosis (including SOD1, GPX1, BID, positively regulates genes involves in skin texture and hydration (including AQP3, Col6A1, FBN1 and modulates the expression of genes involved in skin irritation, DNA damage and aging (including IL1R, PCNA, FOXO3. These findings indicate that the specific N. gaditana extract possesses significant in vitro skin protection activity against induced oxidative stress, and provide new insights into the beneficial role of microalgae bioactive compounds in cosmetic formulations protecting skin from oxidative stress.

  20. [Animal protection without limits? Human-animal relations in between anthropomorphism and objectification].

    Science.gov (United States)

    Grimm, Herwig; Hartnack, Sonja

    2013-01-01

    In view of recent developments in human-animal relations, vets and ethicists face a new problem: On the one hand, animals such as mammals and birds are used extensively and are in danger to be reduced to mere production units e. g. in the agricultural production, measuring devices in laboratories, sports equipment etc. On the other hand, biologically similar animals are perceived as family members or partners and are almost treated like humans. The article summarizes the results of a workshop that dealt with reductionism and anthropomorphism in human-animal relations. Vets and ethicists tackled the question how the unequal treatment of biologically similar animals can be better understood and whether it can be ethically justified. In the first section, the problem of inconsistency in human-animals relations is briefly sketched. The second part of the article addresses the ethics of unequal treatment of similar animals in different contexts. The following section inquires possible solutions and the advantages and disadvantages of biological criteria versus social criteria in animal protection. Finally, the background and reasons for our moral intuitions of injustice associated with the inconsistencies in human-animal relations are outlined. This fourth section refers to the presentation of Peter Kunzmann during the workshop on the unequal treatment of equals.The article closes with some general remarks on the issue. One main result of the workshop can be stated as follows: Due to the fact that the various human-animal relations gain their ethical justification from different ethical reasons, the unequal treatment of similar animals in different contexts is not ethically wrong per se. However, every intrusive dealing or interaction with animals is in itself in need of ethical justification.

  1. Physical-Chemical Basis of the Protection of Slowly Frozen Human Erythrocytes by Glycerol

    Science.gov (United States)

    Rall, W. F.; Mazur, Peter; Souzu, Hiroshi

    1978-01-01

    One theory of freezing damage suggests that slowly cooled cells are killed by being exposed to increasing concentrations of electrolytes as the suspending medium freezes. A corollary to this view is that protective additives such as glycerol protect cells by acting colligatively to reduce the electrolyte concentration at any subzero temperature. Recently published phase-diagram data for the ternary system glycerol-NaCl-water by M. L. Shepard et al. (Cryobiology, 13:9-23, 1976), in combination with the data on human red cell survival vs. subzero temperature presented here and in the companion study of Souzu and Mazur (Biophys. J., 23:89-100), permit a precise test of this theory. Appropriate liquidus phase-diagram information for the solutions used in the red cell freezing experiments was obtained by interpolation of the liquidus data of Shepard and his co-workers. The results of phase-diagram analysis of red cell survival indicate that the correlation between the temperature that yields 50% hemolysis (LT50) and the electrolyte concentration attained at that temperature in various concentrations of glycerol is poor. With increasing concentrations of glycerol, the cells were killed at progressively lower concentrations of NaCl. For example, the LT50 for cells frozen in the absence of glycerol corresponds to a NaCl concentration of 12 weight percent (2.4 molal), while for cells frozen in 1.75 M glycerol in buffered saline the LT50 corresponds to 3.0 weight percent NaCl (1.3 molal). The data, in combination with other findings, lead to two conclusions: (a) The protection from glycerol is due to its colligative ability to reduce the concentration of sodium chloride in the external medium, but (b) the protection is less than that expected from colligative effects; apparently glycerol itself can also be a source of damage, probably because it renders the red cells susceptible to osmotic shock during thawing. PMID:667300

  2. Physical-chemical basis of the protection of slowly frozen human erythrocytes by glycerol

    Energy Technology Data Exchange (ETDEWEB)

    Rall, W.F.; Mazur, P.; Souzu, H.

    1978-07-01

    One theory of freezing damage suggests that slowly cooled cells are killed by being exposed to increasing concentrations of electrolytes as the suspending medium freezes. A corollary to this view is that protective additives such as glycerol protect cells by acting colligatively to reduce the electrolyte concentration at any subzero temperature. Recently published phase-diagram data for the ternary system glycerol-NaCl-water by M.L. Shepard et al. (Cryobiology, 13: 9-23, 1976), in combination with the data on human red cell survival vs. subzero temperature presented here and in the companion study of Souzu and Mazur (Biophys. J., 23: 89-100), permit a precise test of this theory. Appropriate liquidus phase-diagram information for the solutions used in the red cell freezing experiments was obtained by interpolation of liquidus data of Shepard and his co-workers. The results of phase-diagram analysis of red cell survival indicate that the correlation between the temperature that yields 50% hemolysis (LT/sub 50/) and the electrolyte concentration attained at that temperature in various concentrations of glycerol is poor. With increasing concentrations of glycerol, the cells were killed at progressively lower concentrations of NaCl. For example, the LT/sub 50/ for cells frozen in the absence of glycerol corresponds to a NaCl concentration of 12 weight percent (2.4 molal), while for cells frozen in 1.75 M glycerol in buffered saline the LT/sub 50/ corresponds to 3.0 weight percent NaCl (1.3 molal). The data, in combination with other findings, lead to two conclusions: (a) The protection from glycerol is due to its colligative ability to reduce the concentration of sodium chloride in the external medium, but (b) the protection is less than that expected from colligative effects; apparently glycerol itself can also be a source of damage, probably because it renders the red cells susceptible to osmotic shock during thawing.

  3. Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime

    Directory of Open Access Journals (Sweden)

    M. Mathy-Hartert

    1995-01-01

    Full Text Available We investigated the effects of the antibiotic ceftazidime (CAZ on the cytolytic action of the neutrophil myeloperoxidase–hydrogen peroxide–chloride anion system (MPO/H2O2/Cl−. In this system, myeloperoxidase catalyses the conversion of H2O2 and CI− to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC were capable of taking up active MPO. In presence of H2O2 (10−4 M, this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of 51Cr from HUVEC and expressed as an index of cytotoxicity (IC. Dose dependent protection was obtained for CAZ concentrations ranging from 10−5 to 10−3 M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H2O2, but when cytolysis was achieved with H2O2 or O2− generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H2O2 was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon. So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis.

  4. Protection against Cutaneous Leishmaniasis Induced by Recombinant Antigens in Murine and Nonhuman Primate Models of the Human Disease

    Science.gov (United States)

    Campos-Neto, Antonio; Porrozzi, Renato; Greeson, Kay; Coler, Rhea N.; Webb, John R.; Seiky, Yasir A. W.; Reed, Steven G.; Grimaldi, Gabriel

    2001-01-01

    Leishmaniasis affects approximately 2 million people each year throughout the world. This high incidence is due in part to the lack of an efficacious vaccine. We present evidence that the recombinant leishmanial antigens LmSTI1 and TSA, which we identified and characterized previously, induce excellent protection in both murine and nonhuman primate (rhesus monkey) models of human cutaneous leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an animal model that is evolutionarily close to humans qualifies this antigen combination as a promising candidate subunit vaccine against human leishmaniasis. PMID:11349082

  5. Remifentanil protects human keratinocytes against hypoxia-reoxygenation injury through activation of autophagy.

    Directory of Open Access Journals (Sweden)

    Jae-Young Kwon

    Full Text Available The proliferation, differentiation, and migration of keratinocytes are essential in the early stages of wound healing. Hypoxia-Reoxygenation (H/R injury to keratinocytes can occur in various stressful environments such as surgery, trauma, and various forms of ulcers. The effects of remifentanil on human keratinocytes under hypoxia-reoxygenation have not been fully studied. Therefore, we investigated the effects of remifentanil on the proliferation, apoptosis, and autophagic activation of human keratinocytes during hypoxic-reoxygenation. Human keratinocytes were cultured under 1% oxygen tension for 24 h. The cells were then treated with various concentrations of remifentanil (0.01, 0.1, 0.5, and 1 ng/mL for 2 h. Thereafter, the cells were reoxygenated for 12 h at 37°C. We measured cell viability via MTT assay. Using quantitative real-time PCR and western blot analysis, we measured the expression levels of proteins associated with apoptosis and autophagy. Quantification of apoptotic cells was performed using flow cytometer analysis and autophagic vacuoles were observed under a fluorescence microscope. Remifentanil treatment brought about an increase in the proliferation of human keratinocytes damaged by hypoxia-reoxygenation and decreased the apoptotic cell death, enhancing autophagic activity. However, the autophagy pathway inhibitor 3-MA inhibited the protective effect of remifentanil in hypoxia-reoxygenation injury. In conclusion, the current study demonstrated that remifentanil treatment stimulated autophagy and reduced apoptotic cell death in a hypoxia-reoxygenation model of human keratinocytes. Our results provide additional insights into the relationship between apoptosis and autophagy.

  6. Impacts of Community Forest Management and Strictly Protected Areas on Deforestation and Human Well-Being in Madagascar

    DEFF Research Database (Denmark)

    Rasolofoson, Ranaivo Andriarilala

    Protected areas and Community Forest Management (CFM) are among the most widespread interventions to conserve forests in tropical countries. In addition to their impacts on forests and the biodiversity they contain, these interventions also affect human well-being, particularly that of the local...... they contain) and human well-being. However, while scientifically rigorous impact evaluation of programs is well advanced in fields such as development, health and education, it is rare in nature conservation. The rare existing studies focus mostly on protected areas and other interventions, such as CFM......-dimensional nature of human well-being. In this thesis, I aim to investigate the impacts of different conservation interventions on environmental and human well-being outcomes while addressing the challenges to conservation impact evaluation discussed above. My case studies are CFM and strict protection...

  7. Are protected areas required to maintain functional diversity in human-modified landscapes?

    Directory of Open Access Journals (Sweden)

    H Eden W Cottee-Jones

    Full Text Available The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities.

  8. Are protected areas required to maintain functional diversity in human-modified landscapes?

    Science.gov (United States)

    Cottee-Jones, H Eden W; Matthews, Thomas J; Bregman, Tom P; Barua, Maan; Tamuly, Jatin; Whittaker, Robert J

    2015-01-01

    The conversion of forest to agriculture across the world's tropics, and the limited space for protected areas, has increased the need to identify effective conservation strategies in human-modified landscapes. Isolated trees are believed to conserve elements of ecological structure, providing micro-sites for conservation in matrix landscapes, and facilitating seed dispersal and forest restoration. Here we investigate the role of isolated Ficus trees, which are of critical importance to tropical forest ecosystems, in conserving frugivore composition and function in a human-modified landscape in Assam, India. We surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit trees, and 31 other large trees across a range of 32 km from the nearest intact forest. We found that Ficus trees attracted richer and more abundant assemblages of frugivores than the other tree categories. However, incidence function estimates revealed that forest specialist species decreased dramatically within the first kilometre of the forest edge. Despite this, species richness and functional diversity remained consistent across the human-modified landscape, as habitat generalists replaced forest-dependent frugivores, and accounted for most of the ecological function found in Ficus trees near the forest edge. We recommend that isolated Ficus trees are awarded greater conservation status, and suggest that their conservation can support ecologically functional networks of frugivorous bird communities.

  9. Protection effect of cosmetics on human skin under simulated rigorous environment.

    Science.gov (United States)

    Cheng, Yan; Dong, Yi-Yang; Dong, Mei-Xian; Wang, Chao; Su, Ning; Sun, Yuan-Tao; Liu, Juan; Zheng, Hong-Yan; Schrader, Andreas; Rohr, Mathias; Liu, Wei

    2008-02-01

    The efficacy of cosmetics on human skin measured under normal mild laboratory environment might be discounted by exterior environment factors such as wind, UV exposure, etc. Few studies have focused on the 'genuine' efficacy of cosmetics on human skin during exposure to external rigorous environment. The aim of this study was to develop a model for the evaluation of the efficacy of cosmetics on human skin under simulated rigorous environment. We measured skin water content and transepidermal water loss (TEWL) before and after products application under simulated windy and sub-erythema UV exposure treatment in a constant temperature and humidity laboratory. The results showed that the products had higher water content and lower TEWL at 2, 4 and 8 h of products application, and ameliorated the skin moisturization situation after a 3-week continuous use of the products. In addition, the products might protect the skin to maintain the normal water content and TEWL under the simulated windy or sub-erythema UV exposure treatment in our laboratory when compared with untreated area. Our data indicate that this model may provide a more accurate evaluation for the genuine moisturizing effect of cosmetics under external natural climate.

  10. Human Leukocyte Antigen E Contributes to Protect Tumor Cells from Lysis by Natural Killer Cells12

    Science.gov (United States)

    Monaco, Elisa Lo; Tremante, Elisa; Cerboni, Cristina; Melucci, Elisa; Sibilio, Leonardo; Zingoni, Alessandra; Nicotra, Maria Rita; Natali, Pier Giorgio; Giacomini, Patrizio

    2011-01-01

    The nonclassic class I human leukocyte antigen E (HLA-E) molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK) cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3) of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D). Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network. PMID:21969815

  11. Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells.

    Science.gov (United States)

    Lo Monaco, Elisa; Tremante, Elisa; Cerboni, Cristina; Melucci, Elisa; Sibilio, Leonardo; Zingoni, Alessandra; Nicotra, Maria Rita; Natali, Pier Giorgio; Giacomini, Patrizio

    2011-09-01

    The nonclassic class I human leukocyte antigen E (HLA-E) molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK) cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3) of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D). Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network.

  12. Human Leukocyte Antigen E Contributes to Protect Tumor Cells from Lysis by Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Elisa Lo Monaco

    2011-09-01

    Full Text Available The nonclassic class I human leukocyte antigen E (HLA-E molecule engages the inhibitory NKG2A receptor on several cytotoxic effectors, including natural killer (NK cells. Its tissue distribution was claimed to be wider in normal than in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell lines. Herein, these issues were reinvestigated taking advantage of HLA-E-specific antibodies, immunohistochemistry, and biochemical methods detecting intracellular and surface HLA-E regardless of conformation. Contrary to published evidence, HLA-E was detected in a few normal epithelia and in a large fraction (approximately 1/3 of solid tumors, including those derived from HLA-E-negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30 tumor cell lines representative of major lymphoid and nonlymphoid lineages, and in 11 of 11, it was surface-expressed, although in a conformation poorly reactive with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand donors was not required for surface expression but was associated with NKG2A-mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK cells from healthy donors, as demonstrated by antibody-mediated relief of protection in 10% to 20% of the tested target-effector combinations. NKG2A-mediated protection of additional targets became evident on NK effector blocking with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors, and NKG2D. Thus, initial evidence that the long-elusive HLA-E molecule is enhanced by malignant transformation and is functional in tumor cells is presented here, although its importance and precise functional role remain to be addressed in the context of a general understanding of the NK ligand-receptor network.

  13. Dietary tomato paste protects against ultraviolet light-induced erythema in humans.

    Science.gov (United States)

    Stahl, W; Heinrich, U; Wiseman, S; Eichler, O; Sies, H; Tronnier, H

    2001-05-01

    Carotenoids are efficient antioxidants capable of scavenging reactive oxygen species generated under conditions of photooxidative stress. It has been shown that supplementation with high doses of beta-carotene protects skin against UV-induced erythema. This study was designed to investigate whether intervention with a natural dietary source rich in lycopene protects against UV-induced erythema in humans. Tomato paste (40 g), providing approximately 16 mg/d of lycopene, was ingested with 10 g of olive oil over a period of 10 wk by 9 volunteers. Controls (n = 10) received olive oil only. Erythema was induced by illumination of dorsal skin (scapular region) with a solar simulator at the beginning of the study, after 4 wk and after 10 wk. Intensity of erythema was measured by chromatometry; the a-value was determined directly before and 24 h after irradiation. Serum carotenoid levels were measured by HPLC. At the beginning of the study, carotenoid levels did not differ between the two groups. Serum levels of lycopene increased in supplemented subjects; the other carotenoids did not change significantly, and no change in serum carotenoids was observed in the control group. At wk 10, dorsal erythema formation was 40% lower in the group that consumed tomato paste compared with controls (P = 0.02; Wilcoxon-Mann-Whitney test). No significant difference between groups was found at wk 4 of treatment. The data demonstrate that it is feasible to achieve protection against UV light-induced erythema by ingestion of a commonly consumed dietary source of lycopene.

  14. Ethics and data protection in human biomarker studies in environmental health.

    Science.gov (United States)

    Casteleyn, Ludwine; Dumez, Birgit; Van Damme, Karel; Anwar, Wagida A

    2013-08-01

    Human biomarker studies in environmental health are essential tools to study the relationship between health and environment. They should ultimately contribute to a better understanding of environmentally induced adverse health effects and to appropriate preventive actions. To ensure the protection of the rights and dignity of study participants a complex legal and ethical framework is applied, consisting of several international directives, conventions, and guidelines, whether or not translated in domestic laws. Main characteristics of ethics and data protection in studies using biomarkers in the field of environmental health are summarized and current discussions on related questions and bottlenecks highlighted. In the current regulatory context, dominated by the protection of the individual study participant, difficulties are reported due to the different interpretation and implementation of the regulations of concern within and across borders. Advancement of consistency and compatibility is recommended and efforts are ongoing. An increasing demand for secondary use of data and samples poses additional challenges in finding a right balance between the individual rights of the study participants on the one hand and the common interest of, and potential benefit for the public or community at large on the other. Ethics committees could play a key role in assessing problems originating from the sometimes competing needs at individual and societal level. Building trust in science amongst (potential) study participants and within the community allows the inclusion of arguments from the societal perspective. This requires increased attention for respectful communication efforts. Striving for public participation in decision making processes may promote policy relevant research and the related translation of study results into action. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  16. The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

    Science.gov (United States)

    Kelleher, Finnuala

    2004-01-01

    Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions.

  17. Extending Court-Protected Legal Person Status to Non-Human Entities

    Directory of Open Access Journals (Sweden)

    Markus Zimmer

    2017-05-01

    Full Text Available Left unattended, the corrosive effects of trafficking-related corruption have the potential to incrementally erode and eventually destroy the very foundations of legitimate and effective government and the rule of law. We see its fruits manifest worldwide to varying degrees in numerous governments. If this fledgling movement to extend to non-Homo sapiens the status of legal persons with all corresponding rights, duties and liabilities of a living person catches on and that status is institutionalized as justiciable in national and international court systems, it may transform how modern societies value and protect their non-human wildlife and marine resources. The time for such transformation is long overdue.

  18. Redox-active cerium oxide nanoparticles protect human dermal fibroblasts from PQ-induced damage

    Directory of Open Access Journals (Sweden)

    Claudia von Montfort

    2015-04-01

    Full Text Available Recently, it has been published that cerium (Ce oxide nanoparticles (CNP; nanoceria are able to downregulate tumor invasion in cancer cell lines. Redox-active CNP exhibit both selective pro-oxidative and antioxidative properties, the first being responsible for impairment of tumor growth and invasion. A non-toxic and even protective effect of CNP in human dermal fibroblasts (HDF has already been observed. However, the effect on important parameters such as cell death, proliferation and redox state of the cells needs further clarification. Here, we present that nanoceria prevent HDF from reactive oxygen species (ROS-induced cell death and stimulate proliferation due to the antioxidative property of these particles.

  19. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

  20. Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Zhi-gao Sun

    2016-01-01

    Full Text Available The active ingredient of ginseng, ginsenosides Rg1, has been shown to scavenge free radicals and improve antioxidant capacity. This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2. Ginsenosides Rg1 at different concentrations (50 and 100 μM was used to treat H2O2 (150 μM-injured SH-SY5Y cells. Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5Y cells injured by H2O2, diminished the amount of leaked lactate dehydrogenase, and increased superoxide dismutase activity. Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity, and contributed to heat shock protein 70 gene expression, in a dose-dependent manner. These results indicate that ginsenoside Rg1 has protective effects on SH-SY5Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.

  1. Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells.

    Science.gov (United States)

    Sun, Zhi-Gao; Chen, Li-Ping; Wang, Fa-Wei; Xu, Cheng-Yong; Geng, Miao

    2016-07-01

    The active ingredient of ginseng, ginsenosides Rg1, has been shown to scavenge free radicals and improve antioxidant capacity. This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2. Ginsenosides Rg1 at different concentrations (50 and 100 μM) was used to treat H2O2 (150 μM)-injured SH-SY5Y cells. Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5Y cells injured by H2O2, diminished the amount of leaked lactate dehydrogenase, and increased superoxide dismutase activity. Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity, and contributed to heat shock protein 70 gene expression, in a dose-dependent manner. These results indicate that ginsenoside Rg1 has protective effects on SH-SY5Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.

  2. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans.

    Science.gov (United States)

    Yiasemides, Eleni; Sivapirabu, Geetha; Halliday, Gary M; Park, Joohong; Damian, Diona L

    2009-01-01

    Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.

  3. TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage.

    Science.gov (United States)

    Ye, Jing; Lenain, Christelle; Bauwens, Serge; Rizzo, Angela; Saint-Léger, Adelaïde; Poulet, Anaïs; Benarroch, Delphine; Magdinier, Frédérique; Morere, Julia; Amiard, Simon; Verhoeyen, Els; Britton, Sébastien; Calsou, Patrick; Salles, Bernard; Bizard, Anna; Nadal, Marc; Salvati, Erica; Sabatier, Laure; Wu, Yunlin; Biroccio, Annamaria; Londoño-Vallejo, Arturo; Giraud-Panis, Marie-Josèphe; Gilson, Eric

    2010-07-23

    Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Human lactoferrin protects against Streptococcus mutans-induced caries in mice.

    Science.gov (United States)

    Velusamy, S K; Markowitz, K; Fine, D H; Velliyagounder, K

    2016-03-01

    The objective of this study is to evaluate the importance of human lactoferrin (hLF) in an experimental caries induced by Streptococcus mutans in a lactoferrin-knockout (LFKO(-/-)) mouse model compared with C576J/BL wild-type (WT) mice. The WT and LFKO(-/-) mice were infected with S. mutans (1 × 10(8) cells) and/or sham infection. Furthermore, the effect of hLF administration was evaluated in LFKO(-/-) mice infected with S. mutans. Mice were assessed for colonization, salivary pH, and caries development. The results showed that the lactoferrin-knockout infected (LFKO(-/-) I) mice had significantly higher colonization with S. mutans (P = 0.02), lower salivary pH (P = 0.01), and more carious lesions (P = 0.01) when compared to wild-type infected (WTI) mice. In addition, the administration of hLF did not show any evidence of S. mutans colonization as well as carious lesions (P = 0.001) in LFKO(-/-) I mice when compared to untreated LFKO(-/-) I mice. These results show that endogenous LF protects against S. mutans-induced caries and that exogenous hLF can exert a protective effect against caries development. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Response of human skin to ultraviolet radiation: dissociation of erythema and metabolic changes following sunscreen protection

    Energy Technology Data Exchange (ETDEWEB)

    Pearse, A.D.; Marks, R.

    1983-03-01

    After UV irradiation of human skin there is an increase in epidermal and stratum corneum thickness and an increase in the thymidine autoradiographic labeling index. Previously we have demonstrated that persistent exposure to ultraviolet radiation (UVR) alters the distribution and activities of glucose-6-phosphate dehydrogenase (G-6-PDH) and succinic dehydrogenase (SDH) within the epidermis; G-6-PDH activity is increased over the whole epidermis and SDH activity is diminished in the granular cell area but increased in the basal layer. When skin is protected by an efficient sunscreen and irradiated with UVB, there is almost complete inhibition of the erythema normally seen following UVR exposure. In this study we have investigated the cytochemical, cell kinetic, and histometric changes that take place in the epidermis after UVB irradiation, with and without two different types of sunscreen. Some of the histometric and metabolic changes associated with UVB exposure were still evident despite sunscreen protection and the successful blocking of the erythema response. The implications of these findings are discussed together with the use of sunscreens to prevent development of solar damage.

  6. A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.

    Directory of Open Access Journals (Sweden)

    Olivia C Demurtas

    Full Text Available BACKGROUND: The E7 protein of the Human Papillomavirus (HPV type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an active form and in compliance with good manufacturing practices (GMP plays a crucial role for developing effective vaccines. E7-based therapeutic vaccines produced in plants have been shown to be active in tumor regression and protection in pre-clinical models. However, some drawbacks of in whole-plant vaccine production encouraged us to explore the production of the E7-based therapeutic vaccine in Chlamydomonas reinhardtii, an organism easy to grow and transform and fully amenable to GMP guidelines. METHODOLOGY/PRINCIPAL FINDINGS: An expression cassette encoding E7GGG, a mutated, attenuated form of the E7 oncoprotein, alone or as a fusion with affinity tags (His6 or FLAG, under the control of the C. reinhardtii chloroplast psbD 5' UTR and the psbA 3' UTR, was introduced into the C. reinhardtii chloroplast genome by homologous recombination. The protein was mostly soluble and reached 0.12% of total soluble proteins. Affinity purification was optimized and performed for both tagged forms. Induction of specific anti-E7 IgGs and E7-specific T-cell proliferation were detected in C57BL/6 mice vaccinated with total Chlamydomonas extract and with affinity-purified protein. High levels of tumor protection were achieved after challenge with a tumor cell line expressing the E7 protein. CONCLUSIONS: The C. reinhardtii chloroplast is a suitable expression system for the production of the E7GGG protein, in a soluble, immunogenic form. The production in contained and sterile conditions highlights the potential of microalgae as alternative platforms for the production of vaccines for human uses.

  7. Protective effect of desloratadine against oxidative stress in human erythrocytes in vitro.

    Science.gov (United States)

    Sadowska-Woda, Izabela; Sychta, Barbara; Rachel, Marta; Bieszczad-Bedrejczuk, Edyta

    2010-09-01

    Desloratadine (DCL) is a non-sedating antihistamine approved for the treatment of allergic rhinitis or chronic idiopathic urticaria. The objective of this study was to evaluate the potential protective effect of DCL against oxidative stress in human erythrocytes in vitro. Human erythrocytes were oxidized by a water-soluble radical generators-2,2' azobis (2-amidinopropane) hydrochloride (AAPH; 20, 50mM) or tert-butyl hydroperoxide (TBHP; 0.5mM) and the protective effects of DCL (2, 5, 7, 10 and 26μM) on selected oxidative stress markers were investigated. Erythrocytes were divided into aliquots. The first aliquot was incubated for 2h at 37°C with AAPH or TBHP. The other test aliquots were preincubated with selected concentrations of DCL for 30min and followed by AAPH or TBHP incubation for 2h. Malondialdehyde (MDA) content, catalase (CAT) and superoxide dismutase (SOD) activities, as well as hemolysis percentage (H) were measured in all erythrocyte samples. The influence of solvent (0.5% ethanol) on the parameters studied was also checked. Pretreatment with DCL (7, 10, 26μM) could prevent TBHP-induced increase in MDA formation in a concentration-dependent manner. DCL has no influence on CAT activity and it significantly enhanced SOD activity compared to AAPH treatment samples at 7, 10, 26μM. DCL (26μM) also reduced the hemolytic effect on erythrocytes when compared to the erythrocytes exposed to oxidants only. These results suggest a beneficial effect of DCL as an antioxidant, which might be an additional explanation of its therapeutic action. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. A neutralizing human monoclonal antibody protects African Green monkeys from Hendra virus challenge

    Science.gov (United States)

    Bossart, Katharine N.; Geisbert, Thomas W.; Feldmann, Heinz; Zhu, Zhongyu; Feldmann, Friederike; Geisbert, Joan B.; Yan, Lianying; Feng, Yan-Ru; Brining, Doug; Scott, Dana; Wang, Yanping; Dimitrov, Antony S.; Callison, Julie; Chan, Yee-Peng; Hickey, Andrew C.; Dimitrov, Dimiter S.; Broder, Christopher C.; Rockx, Barry

    2012-01-01

    Hendra virus (HeV) is a recently emerged zoonotic paramyxovirus that can cause a severe and often fatal disease in horses and humans. HeV is categorized as a biosafety level 4 agent, which has made the development of animal models and testing of potential therapeutics and vaccines challenging. Infection of African Green monkeys (AGMs) with HeV was recently demonstrated and disease mirrored fatal HeV infection in humans, manifesting as a multisystemic vasculitis with widespread virus replication in vascular tissues and severe pathologic manifestations in the lung, spleen and brain. Here, we demonstrate that m102.4, a potent HeV neutralizing human monoclonal antibody (hmAb), can protect AGMs from disease post infection (p.i.) with HeV. Fourteen AGMs were challenged intratracheally with a lethal dose of HeV and twelve subjects were infused twice with a 100 mg dose of m102.4 beginning at either 10 hr, 24 hr or 72 hr p.i. and again approximately 48 hrs later. The presence of viral RNA, infectious virus and HeV-specific immune responses demonstrated that all subjects were infected following challenge. All twelve AGMs that received m102.4 survived infection; whereas the untreated control subjects succumbed to disease on day 8 p.i.. Animals in the 72 hr treatment group exhibited neurological signs of disease but all animals started to recover by day 16 p.i.. These results represent successful post-exposure in vivo efficacy by an investigational drug against HeV and highlight the potential impact a hmAb can have on human disease. PMID:22013123

  9. OASIS/CREB3L1 is induced by endoplasmic reticulum stress in human glioma cell lines and contributes to the unfolded protein response, extracellular matrix production and cell migration.

    Directory of Open Access Journals (Sweden)

    Ravi N Vellanki

    Full Text Available OASIS is a transcription factor similar to ATF6 that is activated by endoplasmic reticulum stress. In this study we investigated the expression of OASIS in human glioma cell lines and the effect of OASIS knock-down on the ER stress response and cell migration. OASIS mRNA was detected in three distinct glioma cell lines (U373, A172 and U87 and expression levels were increased upon treatment with ER stress-inducing compounds in the U373 and U87 lines. OASIS protein, which is glycosylated on Asn-513, was detected in the U373 and U87 glioma lines at low levels in control cells and protein expression was induced by ER stress. Knock-down of OASIS in human glioma cell lines resulted in an attenuated unfolded protein response to ER stress (reduced GRP78/BiP and GRP94 induction and decreased expression of chondroitin sulfate proteoglycan extracellular matrix proteins, but induction of the collagen gene Col1a1 was unaffected. Cells in which OASIS was knocked-down exhibited altered cell morphology and reduced cell migration. These results suggest that OASIS is important for the ER stress response and maintenance of some extracellular matrix proteins in human glioma cells.

  10. Biorepository regulatory frameworks: building parallel resources that both promote scientific investigation and protect human subjects.

    Science.gov (United States)

    Marko-Varga, György; Baker, Mark S; Boja, Emily S; Rodriguez, Henry; Fehniger, Thomas E

    2014-12-05

    Clinical samples contained in biorepositories represent an important resource for investigating the many factors that drive human biology. The biological and chemical markers contained in clinical samples provide important measures of health and disease that when combined with such medical evaluation data can aid in decision making by physicians. Nearly all disciplines in medicine and every "omic" depend upon the readouts obtained from such samples, whether the measured analyte is a gene, a protein, a lipid, or a metabolite. There are many steps in sample processing, storage, and management that need to understood by the researchers who utilize biorepositories in their own work. These include not only the preservation of the desired analytes in the sample but also good understanding of the moral and legal framework required for subject protection irrespective of where the samples have been collected. Today there is a great deal of effort in the community to align and standardize both the methodology of sample collection and storage performed in different locations and the necessary frameworks of subject protection including informed consent and institutional review of the studies being performed. There is a growing trend in developing biorepositories around the focus of large population-based studies that address both active and silent nonsymptomatic disease. Logistically these studies generate large numbers of clinical samples and practically place increasing demand upon health care systems to provide uniform sample handling, processing, storage, and documentation of both the sample and the subject as well to ensure that safeguards exist to protect the rights of the study subjects for deciding upon the fates of their samples. Currently the authority to regulate the entire scope of biorepository usage exists as national practice in law in only a few countries. Such legal protection is a necessary component within the framework of biorepositories, both now and in

  11. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Yoon Hee Cho

    2016-02-01

    Full Text Available Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM, a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL, the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  12. N-acyl-homoserine lactones-producing bacteria protect plants against plant and human pathogens.

    Science.gov (United States)

    Hernández-Reyes, Casandra; Schenk, Sebastian T; Neumann, Christina; Kogel, Karl-Heinz; Schikora, Adam

    2014-11-01

    The implementation of beneficial microorganisms for plant protection has a long history. Many rhizobia bacteria are able to influence the immune system of host plants by inducing resistance towards pathogenic microorganisms. In this report, we present a translational approach in which we demonstrate the resistance-inducing effect of Ensifer meliloti (Sinorhizobium meliloti) on crop plants that have a significant impact on the worldwide economy and on human nutrition. Ensifer meliloti is usually associated with root nodulation in legumes and nitrogen fixation. Here, we suggest that the ability of S. meliloti to induce resistance depends on the production of the quorum-sensing molecule, oxo-C14-HSL. The capacity to enhanced resistance provides a possibility to the use these beneficial bacteria in agriculture. Using the Arabidopsis-Salmonella model, we also demonstrate that the application of N-acyl-homoserine lactones-producing bacteria could be a successful strategy to prevent plant-originated infections with human pathogens. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  13. New World Health Organization guidance helps protect breastfeeding as a human right.

    Science.gov (United States)

    Grummer-Strawn, Laurence M; Zehner, Elizabeth; Stahlhofer, Marcus; Lutter, Chessa; Clark, David; Sterken, Elisabeth; Harutyunyan, Susanna; Ransom, Elizabeth I

    2017-10-01

    Written by the WHO/UNICEF NetCode author group, the comment focuses on the need to protect families from promotion of breast-milk substitutes and highlights new WHO Guidance on Ending Inappropriate Promotion of Foods for Infants and Young Children. The World Health Assembly welcomed this Guidance in 2016 and has called on all countries to adopt and implement the Guidance recommendations. NetCode, the Network for Global Monitoring and Support for Implementation of the International Code of Marketing of Breast-milk Substitutes and Subsequent Relevant World Health Assembly Resolutions, is led by the World Health Organization and the United Nations Children's Fund. NetCode members include the International Baby Food Action Network, World Alliance for Breastfeeding Action, Helen Keller International, Save the Children, and the WHO Collaborating Center at Metropol University. The comment frames the issue as a human rights issue for women and children, as articulated by a statement from the United Nations Office of the High Commissioner for Human Rights. © 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

  14. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

    Science.gov (United States)

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-02-19

    Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  15. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Liz Carmem Silva-Pereira

    2014-09-01

    Full Text Available Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

  16. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

    Science.gov (United States)

    Albuquerque, Rosyana V; Malcher, Nívea S; Amado, Lílian L; Coleman, Michael D; Dos Santos, Danielle C; Borges, Rosivaldo Sa; Valente, Sebastião Aldo S; Valente, Vera C; Monteiro, Marta Chagas

    2015-01-01

    Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDS-NHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  17. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

    Directory of Open Access Journals (Sweden)

    Rosyana V Albuquerque

    Full Text Available Dapsone (DDS hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV on DDS hydroxylamine (DDS-NHOH mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET, but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT activity and reactive oxygen species (ROS generation, but did not alter superoxide dismutase (SOD activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  18. A multivalent and cross-protective vaccine strategy against arenaviruses associated with human disease.

    Directory of Open Access Journals (Sweden)

    Maya F Kotturi

    2009-12-01

    Full Text Available Arenaviruses are the causative pathogens of severe hemorrhagic fever and aseptic meningitis in humans, for which no licensed vaccines are currently available. Pathogen heterogeneity within the Arenaviridae family poses a significant challenge for vaccine development. The main hypothesis we tested in the present study was whether it is possible to design a universal vaccine strategy capable of inducing simultaneous HLA-restricted CD8+ T cell responses against 7 pathogenic arenaviruses (including the lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses, either through the identification of widely conserved epitopes, or by the identification of a collection of epitopes derived from multiple arenavirus species. By inoculating HLA transgenic mice with a panel of recombinant vaccinia viruses (rVACVs expressing the different arenavirus proteins, we identified 10 HLA-A02 and 10 HLA-A03-restricted epitopes that are naturally processed in human antigen-presenting cells. For some of these epitopes we were able to demonstrate cross-reactive CD8+ T cell responses, further increasing the coverage afforded by the epitope set against each different arenavirus species. Importantly, we showed that immunization of HLA transgenic mice with an epitope cocktail generated simultaneous CD8+ T cell responses against all 7 arenaviruses, and protected mice against challenge with rVACVs expressing either Old or New World arenavirus glycoproteins. In conclusion, the set of identified epitopes allows broad, non-ethnically biased coverage of all 7 viral species targeted by our studies.

  19. Protecting the human right to freedom of expression in international law.

    Science.gov (United States)

    Howie, Emily

    2017-11-10

    Since its inclusion in Article 19 of the Universal Declaration of Human Rights, the right to freedom of opinion and expression has been protected in all of the relevant international human rights treaties. In international law, freedom to express opinions and ideas is considered essential at both an individual level, insofar as it contributes to the full development of a person, and being a foundation stone of democratic society. Free speech is a necessary precondition to the enjoyment of other rights, such as the right to vote, free assembly and freedom of association, and is essential to ensure press freedom. However, there is a clear and worrying global trend, including in western democracies, of governments limiting vibrant discussion and debate within civil society and among civil society, political leaders and government. Two examples illustrate this trend. First, anti-protest laws in Australia and the United States threaten the ability of people to stand together and express views on issues they care deeply about. Secondly, metadata retention laws jeopardise press freedom by undermining the confidentiality of journalists' sources and dissuading people from speaking freely on matters of public importance.

  20. Terrestrial mammal assemblages in protected and human impacted areas in Northern Brazilian Amazonia

    Directory of Open Access Journals (Sweden)

    Rodolfo Burgos de Luna

    2017-10-01

    Full Text Available Mammal communities in the vicinity of human settlements are often subject to subsistence hunting and retaliatory killings. We used fourteen digital camera traps equipped with infrared triggers to sample the medium-sized and large mammal communities for ca. 34 (±1.64 days per site. Diversity was measured as both Shannon entropy and Fager´s number of moves (NMS, and dominance was quantified using the Berger-Parker index. We used Kruskall-Wallis tests to investigate if there were statistically significant differences in richness, diversity and dominance among the sites. At an overall sampling effort of 1,946 trap days we recorded 216 independent observations of a total of 20 species belonging to 17 genera and 15 families. Richness and diversity appeared to be determined by forest structure, since, independent of the level of human impact, the richest areas were those closest to the ombrophilous forests of southern Guyana shield, closest to central Amazonia, whereas the poorest were at those sites closest to the vegetation mosaics of central Guyana shield. The disappearance of Tayassu pecari from the impacted areas as well as higher relative abundances in the protected areas, albeit not significant, foresees a possible bleak future for the mammalian assemblages in the near future.

  1. Nrf2 Activation Protects against Solar-Simulated Ultraviolet Radiation in Mice and Humans.

    Science.gov (United States)

    Knatko, Elena V; Ibbotson, Sally H; Zhang, Ying; Higgins, Maureen; Fahey, Jed W; Talalay, Paul; Dawe, Robert S; Ferguson, James; Huang, Jeffrey T-J; Clarke, Rosemary; Zheng, Suqing; Saito, Akira; Kalra, Sukirti; Benedict, Andrea L; Honda, Tadashi; Proby, Charlotte M; Dinkova-Kostova, Albena T

    2015-06-01

    The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1β, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation. ©2015 American Association for Cancer Research.

  2. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

    Directory of Open Access Journals (Sweden)

    Zhang Jingdong

    2011-05-01

    Full Text Available Abstract Background β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. Results β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Conclusions Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer.

  3. Identifying the gaps: Armenian health care legislation and human rights in patient care protections.

    Science.gov (United States)

    Zopunyan, Violeta; Krmoyan, Suren; Quinn, Ryan

    2013-12-12

    Since the collapse of the Soviet Union, the Republic of Armenia has undergone an extensive legislative overhaul. Although a number of developments have aimed to improve the quality and accessibility of Armenia's health care system, a host of factors has prevented the country from fully introducing measures to ensure respect for human rights in patient care. In particular, inadequate health care financing continues to oblige patients to make both formal and informal payments to obtain basic medical care and services. More generally, a lack of oversight and monitoring mechanisms has obstructed the implementation of Armenia's commitments to human rights in several international agreements. Within the framework of a broader project on promoting human rights in patient care, research was carried out to examine Armenia’s health care legislation with the aim of identifying gaps in comparison with international and regional standards. This research was designed using the 14 rights enshrined in the European Charter on Patient Rights as guiding principles, along with domestic legal acts relevant to the rights of health care providers. The gaps analysis revealed numerous problems with Armenian legislation governing the relationships between stakeholders in health care service delivery. It also identified several practical inconsistencies with the international legal instruments ratified by the Armenian government. These legislative shortcomings are illustrated by highlighting key health-related rights violations experienced by patients and their health care providers, and by indicating opportunities for improved rights protections. A full list of human rights relevant to patient care and recommendations for promoting them in the Armenian context is provided in Tables 1 and 2. A number of initiatives must be undertaken in order to promote the full spectrum of human rights in patient care in Armenia. This section highlights certain recommendations flowing from the findings of

  4. Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells.

    Science.gov (United States)

    Hua, Xia; Deng, Ruzhi; Li, Jin; Chi, Wei; Su, Zhitao; Lin, Jing; Pflugfelder, Stephen C; Li, De-Quan

    2015-08-01

    L-carnitine suppresses inflammatory responses in human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. In this study, we determined if L-carnitine induces this protective effect through suppression of reactive oxygen species (ROS)-induced oxidative damage in HCECs. Primary HCECs were established from donor limbal explants. A hyperosmolarity dry-eye model was used in which HCECs are cultured in 450 mOsM medium with or without L-carnitine for up to 48 hours. Production of reactive oxygen species (ROS), oxidative damage markers, oxygenases and antioxidative enzymes were analyzed by 2',7'-dichlorofluorescein diacetate (DCFDA) kit, semiquantitative PCR, immunofluorescence, and/or Western blotting. Reactive oxygen species production increased in HCECs upon substitution of the isotonic medium with the hypertonic medium. L-carnitine supplementation partially suppressed this response. Hyperosmolarity increased cytotoxic membrane lipid peroxidation levels; namely, malondialdehyde (MDA) and hydroxynonenal (HNE), as well as mitochondria DNA release along with an increase in 8-OHdG and aconitase-2. Interestingly, these oxidative markers were significantly decreased by coculture with L-carnitine. Hyperosmotic stress also increased the mRNA expression and/or protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), but inhibited the levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), glutathione peroxidase-1 (GPX1), and peroxiredoxin-4 (PRDX4). However, L-carnitine partially reversed this altered imbalance between oxygenases and antioxidant enzymes induced by hyperosmolarity. Our findings demonstrate for the first time that L-carnitine protects HCECs from oxidative stress by lessening the declines in antioxidant enzymes and suppressing ROS production. Such suppression reduces membrane lipid oxidative damage markers and mitochondrial DNA damage.

  5. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice.

    Science.gov (United States)

    Li, Yue-Xiang; Zhao, Hui; Cao, Rui-Yuan; Deng, Yong-Qiang; Han, Jian-Feng; Zhu, Shun-Ya; Ma, Jie; Liu, Long; Qin, E-De; Qin, Cheng-Feng

    2014-05-06

    Human Enterovirus 71 (EV71) has emerged as the leading cause of viral encephalitis in children, especially in the Asia-Pacific regions. EV71 vaccine development is of high priority at present, and neutralization antibodies have been documented to play critical roles during in vitro and in vivo protection against EV71 infection. In this study, a novel strategy to produce EV71 vaccine candidate based on recombinant multiple tandem linear neutralizing epitopes (mTLNE) was proposed. The three well identified EV71 linear neutralizing epitopes in capsid proteins, VP1-SP55, VP1-SP70 and VP2-SP28, were sequentially linked by a Gly-Ser linker ((G4S)3), and expressed in E.coli in fusion with the Trx and His tag at either terminal. The recombinant protein mTLNE was soluble and could be purified by standard affinity chromatography. Following three dosage of immunization in adult mice, EV71-specific IgG and neutralization antibodies were readily induced by recombinant mTLNE. IgG subtyping demonstrated that lgG1 antibodies dominated the mTLNE-induced humoral immune response. Especially, cytokine profiling in spleen cells from the mTLNE-immunized mice revealed high production of IL-4 and IL-6. Finally, in vivo challenge experiments showed that passive transfer with anti-mTLNE sera conferred full protection against lethal EV71 challenge in neonatal mice. Our results demonstrated that this rational designed recombinant mTLNE might have the potential to be further developed as an EV71 vaccine in the future.

  6. Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    János Pálóczi

    2016-01-01

    Full Text Available Background and Aims. Human embryonic stem cell- (hESC- derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days and then on more differentiated cardiomyocytes (6 + 24 days, both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP (10−7, 10−6, and 10−5 M, BNP (10−9, 10−8, and 10−7 M, and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M. Results. SNAP (10−6, 10−5 M significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms.

  7. Assessing Patterns of Human-Wildlife Conflicts and Compensation around a Central Indian Protected Area

    Science.gov (United States)

    Karanth, Krithi K.; Gopalaswamy, Arjun M.; DeFries, Ruth; Ballal, Natasha

    2012-01-01

    Mitigating crop and livestock loss to wildlife and improving compensation distribution are important for conservation efforts in landscapes where people and wildlife co-occur outside protected areas. The lack of rigorously collected spatial data poses a challenge to management efforts to minimize loss and mitigate conflicts. We surveyed 735 households from 347 villages in a 5154 km2 area surrounding Kanha Tiger Reserve in India. We modeled self-reported household crop and livestock loss as a function of agricultural, demographic and environmental factors, and mitigation measures. We also modeled self-reported compensation received by households as a function of demographic factors, conflict type, reporting to authorities, and wildlife species involved. Seventy-three percent of households reported crop loss and 33% livestock loss in the previous year, but less than 8% reported human injury or death. Crop loss was associated with greater number of cropping months per year and proximity to the park. Livestock loss was associated with grazing animals inside the park and proximity to the park. Among mitigation measures only use of protective physical structures were associated with reduced livestock loss. Compensation distribution was more likely for tiger related incidents, and households reporting loss and located in the buffer. Average estimated probability of crop loss was 0.93 and livestock loss was 0.60 for surveyed households. Estimated crop and livestock loss and compensation distribution were higher for households located inside the buffer. Our approach modeled conflict data to aid managers in identifying potential conflict hotspots, influential factors, and spatially maps risk probability of crop and livestock loss. This approach could help focus allocation of conservation efforts and funds directed at conflict prevention and mitigation where high densities of people and wildlife co-occur. PMID:23227173

  8. Assessing patterns of human-wildlife conflicts and compensation around a Central Indian protected area.

    Science.gov (United States)

    Karanth, Krithi K; Gopalaswamy, Arjun M; DeFries, Ruth; Ballal, Natasha

    2012-01-01

    Mitigating crop and livestock loss to wildlife and improving compensation distribution are important for conservation efforts in landscapes where people and wildlife co-occur outside protected areas. The lack of rigorously collected spatial data poses a challenge to management efforts to minimize loss and mitigate conflicts. We surveyed 735 households from 347 villages in a 5154 km(2) area surrounding Kanha Tiger Reserve in India. We modeled self-reported household crop and livestock loss as a function of agricultural, demographic and environmental factors, and mitigation measures. We also modeled self-reported compensation received by households as a function of demographic factors, conflict type, reporting to authorities, and wildlife species involved. Seventy-three percent of households reported crop loss and 33% livestock loss in the previous year, but less than 8% reported human injury or death. Crop loss was associated with greater number of cropping months per year and proximity to the park. Livestock loss was associated with grazing animals inside the park and proximity to the park. Among mitigation measures only use of protective physical structures were associated with reduced livestock loss. Compensation distribution was more likely for tiger related incidents, and households reporting loss and located in the buffer. Average estimated probability of crop loss was 0.93 and livestock loss was 0.60 for surveyed households. Estimated crop and livestock loss and compensation distribution were higher for households located inside the buffer. Our approach modeled conflict data to aid managers in identifying potential conflict hotspots, influential factors, and spatially maps risk probability of crop and livestock loss. This approach could help focus allocation of conservation efforts and funds directed at conflict prevention and mitigation where high densities of people and wildlife co-occur.

  9. Protective effects of remifentanil against H2O2-induced oxidative stress in human osteoblasts.

    Science.gov (United States)

    Yoon, Ji-Young; Kim, Do-Wan; Kim, Eun-Jung; Park, Bong-Soo; Yoon, Ji-Uk; Kim, Hyung-Joon; Park, Jeong-Hoon

    2016-12-01

    Bone injury is common in many clinical situations, such as surgery or trauma. During surgery, excessive reactive oxygen species (ROS) production decreases the quality and quantity of osteoblasts. Remifentanil decreases ROS production, reducing oxidative stress and the inflammatory response. We investigated remifentanil's protective effects against H 2 O 2 -induced oxidative stress in osteoblasts. To investigate the effect of remifentanil on human fetal osteoblast (hFOB) cells, the cells were incubated with 1 ng/ml of remifentanil for 2 h before exposure to H 2 O 2 . For induction of oxidative stress, hFOB cells were then treated with 200 µM H 2 O 2 for 2 h. To evaluate the effect on autophagy, a separate group of cells were incubated with 1 mM 3-methyladenine (3-MA) before treatment with remifentanil and H 2 O 2 . Cell viability and apoptotic cell death were determined via MTT assay and Hoechst staining, respectively. Mineralized matrix formation was visualized using alizarin red S staining. Western blot analysis was used to determine the expression levels of bone-related genes. Cell viability and mineralized matrix formation increased on remifentanil pretreatment before exposure to H 2 O 2 -induced oxidative stress. As determined via western blot analysis, remifentanil pretreatment increased the expression of bone-related genes (Col I, BMP-2, osterix, and TGF-β). However , pretreatment with 3-MA before exposure to remifentanil and H 2 O 2 inhibited remifentanil's protective effects on hFOB cells during oxidative stress. We showed that remifentanil prevents oxidative damage in hFOB cells via a mechanism that may be highly related to autophagy. Further clinical studies are required to investigate its potential as a therapeutic agent.

  10. Assessing patterns of human-wildlife conflicts and compensation around a Central Indian protected area.

    Directory of Open Access Journals (Sweden)

    Krithi K Karanth

    Full Text Available Mitigating crop and livestock loss to wildlife and improving compensation distribution are important for conservation efforts in landscapes where people and wildlife co-occur outside protected areas. The lack of rigorously collected spatial data poses a challenge to management efforts to minimize loss and mitigate conflicts. We surveyed 735 households from 347 villages in a 5154 km(2 area surrounding Kanha Tiger Reserve in India. We modeled self-reported household crop and livestock loss as a function of agricultural, demographic and environmental factors, and mitigation measures. We also modeled self-reported compensation received by households as a function of demographic factors, conflict type, reporting to authorities, and wildlife species involved. Seventy-three percent of households reported crop loss and 33% livestock loss in the previous year, but less than 8% reported human injury or death. Crop loss was associated with greater number of cropping months per year and proximity to the park. Livestock loss was associated with grazing animals inside the park and proximity to the park. Among mitigation measures only use of protective physical structures were associated with reduced livestock loss. Compensation distribution was more likely for tiger related incidents, and households reporting loss and located in the buffer. Average estimated probability of crop loss was 0.93 and livestock loss was 0.60 for surveyed households. Estimated crop and livestock loss and compensation distribution were higher for households located inside the buffer. Our approach modeled conflict data to aid managers in identifying potential conflict hotspots, influential factors, and spatially maps risk probability of crop and livestock loss. This approach could help focus allocation of conservation efforts and funds directed at conflict prevention and mitigation where high densities of people and wildlife co-occur.

  11. Protection against soman or VX poisoning by human butyrylcholinesterase in guinea pigs and cynomolgus monkeys.

    Science.gov (United States)

    Lenz, David E; Maxwell, Donald M; Koplovitz, Irwin; Clark, Connie R; Capacio, Benjamin R; Cerasoli, Douglas M; Federko, James M; Luo, Chunyuan; Saxena, Ashima; Doctor, Bhupendra P; Olson, Carl

    2005-12-15

    Human butyrylcholinesterase (HuBuChE), purified from outdated human plasma, is being evaluated for efficacy against nerve agents in guinea pigs and cynomolgus monkeys. Previous studies in rodents and nonhuman primates demonstrated that pretreatment of animals with enzymes that can scavenge nerve agents could provide significant protection against behavioral and lethal effects of nerve agent intoxication. In preparation for evaluation of efficacy of HuBuChE prior to initiating an investigational new drug (IND) application, the pharmacokinetics of HuBuChE were evaluated in guinea pigs and in cynomolgus monkeys. HuBuChE was injected intramuscularly (i.m.) at two doses, and blood samples were taken to follow the time-course of HuBuChE in blood for up to 168 h after administration. In guinea pigs, the two doses of HuBuChE, 19.9 and 32.5 mg/kg, produced similar times of maximal blood concentration (T(max) of 26.0 and 26.8 h, respectively) and similar elimination half-times (t(1/2) of 64.6 and 75.5 h, respectively). Enzyme levels were still 10-fold over baseline at 72 h. Based on these data, guinea pigs were administered 150 mg/kg of enzyme i.m. and challenged at T(max). Soman or VX doses were approximately 1.5, 2.0 and 2.0 x LD50 administered subcutaneously (s.c.) in sequence at 90-120 min apart. None of the animals displayed signs of organophosphorus (OP) anticholinesterase intoxication at any of the challenge levels, and all survived for the 14-day duration of the experiment. Similar experiments were carried out with cynomolgus monkeys to determine the pharmacokinetics of HuBuChE and its efficacy against soman. The complete survival of nearly all animals tested to date, coupled with the maximal blood concentration and half-life elimination profile obtained for HuBuChE after i.m. injection, provides strong support for the continued development of HuBuChE as a product to protect against nerve agents.

  12. SurR9C84A protects and recovers human cardiomyocytes from hypoxia induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Ashok, Ajay [Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research - C-MMR, Deakin University, Waurn Ponds, Victoria 3216 (Australia); Department of Pathology, Case Western Reserve University, 2103 Cornell Rd. WRB 5128, Cleveland, OH 44106-7288 (United States); Kanwar, Jagat Rakesh [Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research - C-MMR, Deakin University, Waurn Ponds, Victoria 3216 (Australia); Krishnan, Uma Maheswari [Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical & Biotechnology (SCBT), SASTRA University, Thanjavur 613401 (India); Kanwar, Rupinder Kaur, E-mail: rupinder.kanwar@deakin.edu.au [Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research - C-MMR, Deakin University, Waurn Ponds, Victoria 3216 (Australia)

    2017-01-01

    . - Highlights: • Protection/regeneration of dying myocardium post myocardial infarction is important. • Downregulation of survivin induces apoptosis in hypoxic human cardiomyocytes (HCM). • Bio-replenishment with SurR9-C84A reinstates HCM survival, recovery and growth. • SurR9-C84A targets mitochondrial depolarization, fcTnT and ROS generation in HCM. • SurR9-C84A upregulates survivin, PCNA, PI3K/Akt pathway, VEGF and HSP levels. • SurR9-C84A holds promise as a treatment and preventive agent to replenish survivin.

  13. Impacts on the biodiversity by living inside a protected area, Natma Taung National Park, Myanmar; A human perspective

    OpenAIRE

    San, Khin Nyein

    2017-01-01

    Protected areas (PAs) are aimed to maintain or restore the balance in nature. PAs are also an important indicator in measuring the biodiversity loss caused by humans. Global biodiversity is under the long term threats all over the world and we need to understand the behavior of human, ourselves which is challenging the conservation of biodiversity. PAs are usually located in the most remote regions of the countries where people living close to the PAs have poor social status. Local people in ...

  14. Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus†

    OpenAIRE

    Yuan, Lijuan; Kang, S.-Y.; Ward, Lucy A.; To, Thanh L.; Saif, Linda J.

    1998-01-01

    Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were dete...

  15. World Heritage Protection and the Human Right to Development: Reconciling Competing or Complimentary Narratives Using a Human Rights-Based Approach (HRBA?

    Directory of Open Access Journals (Sweden)

    Josephine Gillespie

    2013-07-01

    Full Text Available In the pursuit of the protection of places worthy of World Heritage designation, controls are placed on human activities. Regulations are put in place to curb the extent to which these places of heritage significance might be compromised by inappropriate human uses. For the most part, this conservation exercise takes the form of a regulatory regime that, in reality, imposes localized restrictions on how people interact with the protected site. Such restrictions can come at considerable expense to pre-existing users, and arguably, in some instances, these restrictions may also act to simultaneously restrict “rights”. These rights arise by virtue of a raft of international and regional commitments to human rights that, in essence, aim to preserve human dignity for all. This paper explores the nexus between conservation and development through a “rights” paradigm. Arguably, it is untenable to sustain a situation in which heritage trumps user-rights without due regard for some of the rights articulated within the human rights narrative. Heritage protection must be seen as a question of balance wherein conservation, development and rights are reconciled. It is argued that the adoption of a human rights-based approach (HRBA to conservation may aid in the reconciliation of these goals.

  16. Protective effect of lycopene for oxidative damage in human lens epithelial cells induced by UV

    Directory of Open Access Journals (Sweden)

    Jing-Wen Sun

    2016-05-01

    Full Text Available AIM:To investigate the protective effect and possible mechanisms of lycopene for oxidative damage induced by ultraviolet in cultured human lens epithelial cells(HLEC. METHODS:HLEC was subcultured and divided into negative control group, oxidative injury group, lycopene low dose group and lycopene high dose group. Cell viability was assayed by MTT colorimetric. Cell morphological changes were detected by electron microscope. Reactive oxygen species(ROSlevels were detected with DCFH-DA fluorescent probe. Content of superoxide dismutase(SOD, glutathione peroxidase(GSHand malondialdehyde(MDAin supernatants were detected by spectrophotometer. RESULTS:Lycopene could obviously inhibited UV-induced decline in cell activity, reduce UV-induced ROS generation within HLEC, cause SOD, GSH-Px levels increased and MDA levels decreased.CONCLUSION:Lycopene plays its strong antioxidant role in increasing the intracellular SOD and GSH-Px content levels and decreasing MDA levels, which provide reliable experimental basis for prevent and treatment of cataracts.

  17. Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.

    Science.gov (United States)

    Singh, Bhupendra; Li, Xiurong; Owens, Kjerstin M; Vanniarajan, Ayyasamy; Liang, Ping; Singh, Keshav K

    2015-01-01

    To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells.

  18. Protecting human health and security in digital Europe: how to deal with the "privacy paradox"?

    Science.gov (United States)

    Büschel, Isabell; Mehdi, Rostane; Cammilleri, Anne; Marzouki, Yousri; Elger, Bernice

    2014-09-01

    This article is the result of an international research between law and ethics scholars from Universities in France and Switzerland, who have been closely collaborating with technical experts on the design and use of information and communication technologies in the fields of human health and security. The interdisciplinary approach is a unique feature and guarantees important new insights in the social, ethical and legal implications of these technologies for the individual and society as a whole. Its aim is to shed light on the tension between secrecy and transparency in the digital era. A special focus is put from the perspectives of psychology, medical ethics and European law on the contradiction between individuals' motivations for consented processing of personal data and their fears about unknown disclosure, transferal and sharing of personal data via information and communication technologies (named the "privacy paradox"). Potential benefits and harms for the individual and society resulting from the use of computers, mobile phones, the Internet and social media are being discussed. Furthermore, the authors point out the ethical and legal limitations inherent to the processing of personal data in a democratic society governed by the rule of law. Finally, they seek to demonstrate that the impact of information and communication technology use on the individuals' well-being, the latter being closely correlated with a high level of fundamental rights protection in Europe, is a promising feature of the socalled "e-democracy" as a new way to collectively attribute meaning to large-scale online actions, motivations and ideas.

  19. Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage

    Directory of Open Access Journals (Sweden)

    Massimiliano Gasparrini

    2017-06-01

    Full Text Available Extreme exposure of skin to Ultraviolet A (UVA-radiation may induce a dysregulated production of reactive oxygen species (ROS which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 μg/mL-based formulations supplemented with Coenzyme Q10 (100 μg/mL and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p < 0.05 photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents.

  20. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  1. Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage.

    Science.gov (United States)

    Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Afrin, Sadia; Reboredo-Rodriguez, Patricia; Cianciosi, Danila; Mezzetti, Bruno; Quiles, Josè L; Bompadre, Stefano; Battino, Maurizio; Giampieri, Francesca

    2017-06-14

    Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 μg/mL)-based formulations supplemented with Coenzyme Q10 (100 μg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents.

  2. Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses.

    Science.gov (United States)

    Schriner, Samuel E; Avanesian, Agnesa; Liu, Yanxia; Luesch, Hendrik; Jafari, Mahtab

    2009-09-01

    Rhodiola rosea root has been long used in traditional medical systems in Europe and Asia as an adaptogen to increase an organism's resistance to physical stress. Recent research has demonstrated its ability to improve mental and physical stamina, to improve mood, and to help alleviate high-altitude sickness. We have also recently found that R. rosea is able to extend the life span of Drosophila melanogaster. The mode of action of R. rosea is currently unknown; it has been suggested by some to act as an antioxidant, whereas others have argued that it may actually be a pro-oxidant and act through a hormetic mechanism. We found that R. rosea supplementation could protect cultured cells against ultraviolet light, paraquat, and H(2)O(2). However, it did not alter the levels of the major antioxidant defenses nor did it markedly activate the antioxidant response element or modulate heme-oxygenase-1 expression levels at relevant concentrations. In addition, R. rosea extract was not able to significantly degrade H(2)O(2) in vitro. These results suggest that in human cultured cells R. rosea does not act as an antioxidant and that its mode of action cannot be sufficiently explained through a pro-oxidant hormetic mechanism.

  3. Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis.

    Science.gov (United States)

    Darendelioglu, Ekrem; Aykutoglu, Gurkan; Tartik, Musa; Baydas, Giyasettin

    2016-05-01

    Chronic cardiovascular and neurodegenerative complications induced by hyperhomocysteinemia have been most relatively associated with endothelial cell injury. Elevated homocysteine (Hcy) generates reactive oxygen species (ROS) accompanying with oxidative stress which is hallmarks of the molecular mechanisms responsible for cardiovascular disease. Propolis is a natural product, obtained by honeybee from various oils, pollens, special resins and wax materials, conventionally used with the purpose of treatment by folks Propolis has various biological activities and powerful antioxidant capacity. The flavonoids and phenolic acids, most bioactive components of propolis, have superior antioxidant ability to defend cell from free radicals. This study was designed to examine the protective effects of Turkish propolis (from east of country) on Hcy induced ROS production and apoptosis in human vascular endothelial cells (HUVECs). According to results, co-treatment of HUVECs with propolis decreased Hcy-induced ROS overproduction and lipid peroxidation (LPO) levels. Furthermore, overproductions of Bax, caspase-9 and caspase-3 protein, elevation of cytochrome c release in Hcy-treated HUVECs were significantly reduced by propolis. It was concluded that propolis has cytoprotective ability against cytotoxic effects of high Hcy in HUVECs. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.

    Directory of Open Access Journals (Sweden)

    Dominick J Laddy

    Full Text Available BACKGROUND: The persistent evolution of highly pathogenic avian influenza (HPAI highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. METHODS AND FINDINGS: Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA, N1 neuraminidase (pN1NA, and nucleoprotein antigen (pNP. Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40 were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. CONCLUSIONS: By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the

  5. Simvastatin Protects Human Melanocytes from H2O2-Induced Oxidative Stress by Activating Nrf2.

    Science.gov (United States)

    Chang, Yuqian; Li, Shuli; Guo, Weinan; Yang, Yuqi; Zhang, Weigang; Zhang, Qian; He, Yuanmin; Yi, Xiuli; Cui, Tingting; An, Yawen; Song, Pu; Jian, Zhe; Liu, Ling; Li, Kai; Wang, Gang; Gao, Tianwen; Wang, Lin; Li, Chunying

    2017-06-01

    The prevention of hydrogen peroxide (H2O2)-induced oxidative stress has proved to be beneficial to vitiligo patients. Simvastatin possesses antioxidative capacity and has shown protective effect in various oxidative stress-related diseases. However, whether simvastatin can protect human melanocytes against oxidative stress has not been investigated. In this study, we initially found that pretreatment with 0.1 μmol/L to 1.0 μmol/L simvastatin led to increased cell viability and decreased cell apoptosis of melanocytes in response to H2O2. In addition, simvastatin was able to potentiate the activity of antioxidant enzymes and lessen intracellular reactive oxygen species accumulation. Furthermore, we found that simvastatin promoted the activation of nuclear erythroid 2-related factor (Nrf2) and that knockdown of Nrf2 abolished the protective effect of simvastatin against H2O2-induced oxidative damage. More importantly, the mutual enhancement between mitogen-activated protein kinase pathways and p62 contributed to simvastatin-induced Nrf2 activation in melanocytes. Finally, simvastatin showed more antioxidative capacity and better protective effect than aspirin in H2O2-treated melanocytes. Taken together, our results show that simvastatin protects human melanocytes from H2O2-induced oxidative stress by activating Nrf2, thus supporting simvastatin as a potential therapeutic agent for vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

    Directory of Open Access Journals (Sweden)

    Budnik Lygia T

    2012-01-01

    Full Text Available Abstract Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage. The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49, P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl

  7. Integrating human and environmental health in antibiotic risk assessment: A critical analysis of protection goals, species sensitivity and antimicrobial resistance.

    Science.gov (United States)

    Le Page, Gareth; Gunnarsson, Lina; Snape, Jason; Tyler, Charles R

    2017-12-01

    Antibiotics are vital in the treatment of bacterial infectious diseases but when released into the environment they may impact non-target organisms that perform vital ecosystem services and enhance antimicrobial resistance development with significant consequences for human health. We evaluate whether the current environmental risk assessment regulatory guidance is protective of antibiotic impacts on the environment, protective of antimicrobial resistance, and propose science-based protection goals for antibiotic manufacturing discharges. A review and meta-analysis was conducted of aquatic ecotoxicity data for antibiotics and for minimum selective concentration data derived from clinically relevant bacteria. Relative species sensitivity was investigated applying general linear models, and predicted no effect concentrations were generated for toxicity to aquatic organisms and compared with predicted no effect concentrations for resistance development. Prokaryotes were most sensitive to antibiotics but the range of sensitivities spanned up to several orders of magnitude. We show reliance on one species of (cyano)bacteria and the 'activated sludge respiration inhibition test' is not sufficient to set protection levels for the environment. Individually, neither traditional aquatic predicted no effect concentrations nor predicted no effect concentrations suggested to safeguard for antimicrobial resistance, protect against environmental or human health effects (via antimicrobial resistance development). Including data from clinically relevant bacteria and also more species of environmentally relevant bacteria in the regulatory framework would help in defining safe discharge concentrations for antibiotics for patient use and manufacturing that would protect environmental and human health. It would also support ending unnecessary testing on metazoan species. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis.

    Science.gov (United States)

    Riessland, Markus; Kaczmarek, Anna; Schneider, Svenja; Swoboda, Kathryn J; Löhr, Heiko; Bradler, Cathleen; Grysko, Vanessa; Dimitriadi, Maria; Hosseinibarkooie, Seyyedmohsen; Torres-Benito, Laura; Peters, Miriam; Upadhyay, Aaradhita; Biglari, Nasim; Kröber, Sandra; Hölker, Irmgard; Garbes, Lutz; Gilissen, Christian; Hoischen, Alexander; Nürnberg, Gudrun; Nürnberg, Peter; Walter, Michael; Rigo, Frank; Bennett, C Frank; Kye, Min Jeong; Hart, Anne C; Hammerschmidt, Matthias; Kloppenburg, Peter; Wirth, Brunhilde

    2017-02-02

    Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca 2+ -dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Lin JF

    2017-05-01

    cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1 was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis.Conclusion: Collectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction. Keywords: autophagy inhibition, autophagy related genes, apoptosis, cisplatin resistance, human urinary bladder urothelial carcinoma, lentiviral-based shRNA

  10. The protective effect of geniposide on human neuroblastoma cells in the presence of formaldehyde

    Science.gov (United States)

    2013-01-01

    Background Formaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline. Methods In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored. Results Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment. Conclusions Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione

  11. Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Nissen, Thomas Nørrelykke; Fredslund, Sine

    2016-01-01

    No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well......-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group...

  12. EUROPEAN COURT OF HUMAN RIGHTS AS THE GUARANTOR OF LEGAL PROTECTION OF A HUMAN IN THE FIELD OF AVIATION ACTIVITIES OF UKRAINE

    Directory of Open Access Journals (Sweden)

    Yuriy Pyvovar

    2017-11-01

    Full Text Available Purpose: The effectiveness of human rights protection in the Council of Europe largely depends on activities of the European Court, which demonstrates high standards of justice, particularly in matters of human rights protection in the field of aviation activities. The article offers a critical assessment of Ukrainian national legislation in terms of its internal legal consistency and compliance with international legal acts. Methods: The methods of legal analysis are used to study court decisions in the aviation field; methods of comparative legal analysis, forecasting and dialectical - in the study of problems in the further improvement of Ukrainian legislation. Also in article applied the theory of legal comparative, approaches to applying the analogy of legal and law in process of making decisions on similar court cases. Results: The article deals with the analysis of the European Court of Human Rights jurisdiction on cases of protection of human rights in the field of aviation activities. Two groups of cases in which Ukraine is a defendant are identified: a cases of international concern (in particular the Malaysia Airlines’ Boeing 777-200ER crash; b cases of national character (citizens of Ukraine against the State of Ukraine. The author's position on deciding the cases in the field of aviation activities is based on the principles of respect for the European Convention on Human Rights, 1950. Discussion: The conclusion about the necessity of amending some national laws, taking into account the legal positions of the European Court (in particular, regarding the right of airlines workers to strike is made, and the fact that the issues of States and airlines activities to respect human and civil rights in the field of aviation activities are covered by jurisdiction of the European Court of Human Rights and occupy an important place in its practice is indicated.

  13. Human Adipose Tissue Conditioned Media from Lean Subjects Is Protective against H2O2 Induced Neurotoxicity in Human SH-SY5Y Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Zhongxiao Wan

    2015-01-01

    Full Text Available Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1 Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2 To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM, SP600125 (5 µM and LY29400 (20 µM partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes.

  14. The politics of protection: aid, human rights discourse, and power relations in Kyaka II settlement, Uganda.

    Science.gov (United States)

    Clark-Kazak, Christina R

    2010-01-01

    This paper explores the conceptualisation and application of 'protection' by the United Nations High Commissioner (UNHCR), Ugandan government, and Congolese refugees in Kyaka II refugee settlement, Uganda. Analysing the origins and consequences of a demonstration against school fees, and drawing on other ethnographic data, it explores how different interpretations of this incident reflect different conceptions of, and approaches to, protection. Ugandan government officials viewed the demonstration as a security incident; Congolese and Ugandan adults responded with increased monitoring and 'sheltering' of children and young people; students justified the demonstration as a legitimate manifestation of their rights; while UNHCR promoted assistance and resettlement. The paper argues that prevailing protection responses, including 'sensitisation', sheltering, and resettlement, are de-contextualised from daily realities and fail to address the underlying power relations that undermine protection. It concludes with recommendations on how international refugee agencies can reorient assistance to address protection concerns in refugee contexts.

  15. Biospheric Life Support - integrating biological regeneration into protection of humans in space.

    Science.gov (United States)

    Rocha, Mauricio; Iha, Koshun

    2016-07-01

    retirement (2016). The extension will allow partner agencies to deploy new experiments there, resuming basic research focusing more forward-looking goals. For deep-space, since consumables logistics becomes more difficult- and habitability an issue, with diminishing Earth's view, further research has been recommended. Four major areas have been identified for human protection: (1) radiation mitigation; (2) highly recyclable bio-regenerative (BR) LSS; (3) micro-gravity countermeasures- including artificial gravity (AG), and (4) psychological safety. To contribute to the efforts to address these issues, a basic lab/virtual iterative research has been proposed, assuming (in a worst case scenario) that: I) It won't be possible to send people to long deep space missions, safely, with the current (low quality of life) support technology (ISS micro-gravity 'up-gradings'); II) The alternative to implant a Mars surface human supportive biosphere would also not be possible, due to environmental/ evolutionary restraints (life could adapt and survive, but not necessarily to favor humans). From the above considerations arises the question: Would an average approach be possible where, by applying the artificial gravity concept to S/Cs, a fragment of Earth bio-regenerative environment could be integrated inside reusable manned vehicles- thus enhancing its habitability/autonomy in long deep space missions? For this research question a provisory answer/hypothesis has been provided. And to test it, a small AG+BR bench simulator (plus computer methods) has been devised.

  16. Conformal Ablative Thermal Protection System for Planetary and Human Exploration Missions

    Science.gov (United States)

    Beck, R.; Arnold, J.; Gasch, M.; Stackpole, M.; Wercinski, R.; Venkatapathy, E.; Fan, W.; Thornton, J; Szalai, C.

    2012-01-01

    The Office of Chief Technologist (OCT), NASA has identified the need for research and technology development in part from NASAs Strategic Goal 3.3 of the NASA Strategic Plan to develop and demonstrate the critical technologies that will make NASAs exploration, science, and discovery missions more affordable and more capable. Furthermore, the Game Changing Development Program (GCDP) is a primary avenue to achieve the Agencys 2011 strategic goal to Create the innovative new space technologies for our exploration, science, and economic future. In addition, recently released NASA Space Technology Roadmaps and Priorities, by the National Research Council (NRC) of the National Academy of Sciences stresses the need for NASA to invest in the very near term in specific EDL technologies. The report points out the following challenges (Page 2-38 of the pre-publication copy released on February 1, 2012): Mass to Surface: Develop the ability to deliver more payload to the destination. NASA's future missions will require ever-greater mass delivery capability in order to place scientifically significant instrument packages on distant bodies of interest, to facilitate sample returns from bodies of interest, and to enable human exploration of planets such as Mars. As the maximum mass that can be delivered to an entry interface is fixed for a given launch system and trajectory design, the mass delivered to the surface will require reductions in spacecraft structural mass more efficient, lighter thermal protection systems more efficient lighter propulsion systems and lighter, more efficient deceleration systems. Surface Access: Increase the ability to land at a variety of planetary locales and at a variety of times. Access to specific sites can be achieved via landing at a specific location(s) or transit from a single designated landing location, but it is currently infeasible to transit long distances and through extremely rugged terrain, requiring landing close to the site of

  17. The UNESCO Universal Declaration on Bioethics and Human Rights: protecting future generations and the quest for a global consensus.

    Science.gov (United States)

    Salako, Solomon E

    2008-12-01

    Since the coining of the term 'ectogenesis' by Haldane in 1924, we have witnessed sensational biotechnological triumphs such as in vitro fertilisation, the cloning of "Dolly" the sheep, and the publication of the human genetic code. These triumphs mix benefits with portents in one seamless package. The object of this article is to assess critically the Universal Declaration on Bioethics and Human Rights. It is argued that the Declaration is not a suitable international instrument for regulating biotechnology and protecting future generations. Finally, the feasibility of a legally binding international instrument based on a global consensus is evaluated.

  18. Interactions between International Humanitarian Law and International Human Rights Law for the protection of Economic, Social and Cultural Rights

    Directory of Open Access Journals (Sweden)

    Koldo Casla

    2012-01-01

    Full Text Available Economic, Social and Cultural Rights (ESCR are at risk on the battlefield. Thus, human rights lawyers must look for legal means to guarantee the best possible protection of these rights in case of war. It is generally accepted nowadays that both International Humanitarian Law (IHL and International Human Rights Law (IHRL are applicable during armed conflicts. Adding on that and based on a procedural and substantive legal analysis, this paper claims that both IHL and IHRL constantly interact in a relation of synergy or norms.

  19. Leaving the Nest: The Evolution of CHRPP (the Course of Human Participant Protection) | Quitter le nid : l’évolution du cours d’éthique sur la protection des participants humains

    National Research Council Canada - National Science Library

    Stockley, Denise; Balkwill, Laura-Lee; Hoessler, Carolyn

    2016-01-01

    Four years ago [Institution Name] University launched an online tutorial called CHRPP, the Course in Human Research Participant Protection, and published a paper based about its purpose, design, and usability in (Authors, 2009...

  20. Salidroside protects against premature senescence induced by ultraviolet B irradiation in human dermal fibroblasts.

    Science.gov (United States)

    Mao, G-X; Xing, W-M; Wen, X-L; Jia, B-B; Yang, Z-X; Wang, Y-Z; Jin, X-Q; Wang, G-F; Yan, J

    2015-06-01

    Salidroside, the predominant component of a Chinese herbal medicine, Rhodiola rosea L., becomes an attractive bio-agent due to its multifunction. Although it is well proposed that this herbal medicine may have photoprotective effect according to the folk hearsay, the direct supportive experimental evidences linking the drug with skin ageing have rarely been reported so far. The study was conducted to investigate the photoprotective role of salidrosdie and its related mechanisms in vitro. First, a premature senescence model induced by UVB irradiation (250 mJ cm(-2)) in human dermal fibroblasts (HDFs) was established, and senescent phenotypes were evaluated by cell morphology, cell proliferation, senescence-associated beta-galactosidase (SA-β-gal) activity and cell cycle distribution. Then the photoprotective effect of salidroside was investigated. Cells were pre-treated with various doses of salidroside (1, 5 and 10 μM) followed by the sublethal dosage of UVB exposure and then were harvested for various detections, including senescence-associated phenotypes and molecules, alteration of oxidative stress, matrix metalloproteinase-1 (MMP-1) secretion and inflammatory response. Pre-treatment of salidroside dose dependently reversed the senescent state of HDFs induced by UVB as evidenced by elevated cell viability, decreased SA-β-gal activity and relieving of G1/G0 cell cycle arrest. UVB-induced increased protein expression of cyclin-dependent kinase (CDK) inhibitors p21(WAF) (1) and p16(INK) (4) was also repressed by salidrosdie treatment in a dose-dependent manner. Meanwhile, the increment of malondialdehyde (MDA) level in UVB-irradiated HDFs was inhibited upon salidroside treatment. Additionally, salidroside significantly attenuated UVB-induced synthesis of MMP-1 as well as the production of IL-6 and TNF-α in HDFs. Our data provided the evidences for the protective role of salidroside against UVB-induced premature senescence in HDFs probably via its anti

  1. PROTECTION OF HUMAN RIGHTS AGAINST THE ADVERSE IMPACT OF TRANSNATIONAL CORPORATIONS AND OTHER BUSINESS ENTERPRISES: DILEMMAS OF INTERNATIONAL COMMUNITY

    Directory of Open Access Journals (Sweden)

    Machoňová-Schellongová Ivana

    2015-12-01

    Full Text Available There is no doubt about an impact of corporate and business operations on human rights, both positive and negative. Growing influence of corporations, power shift between business and states, as well as the complex nature of corporate governance and transnational operations require international regulations. International community undertook numerous initiatives, the most significant and recent being the United Nations Guiding Principles on Business and Human Rights [2011], embraced by States, corporations and civil society as a “milestone“ in business and human rights agenda. While being a  useful comprehensive set of guidelines, Principles are lacking the legally binding force and any monitoring or complaints mechanism. Therefore, there are growing calls for a legally binding treaty to stipulate clearly human rights obligations of States/businesses vis-à-vis human rights and fill the protection gap for victims of corporate abuses. A newly established working group by the Human Rights Council has started to negotiate terms of reference of such a treaty in June 2015. However, meaningful negotiations are threatened by many factors, including the negative approach of US, EU and other developed States along with the corporate sector advocating for stronger implementation of Principles instead. This article aims to describe efforts of international community to prevent and eliminate a  negative impact of corporate activities on human rights. It shows different approaches and highlights some challenges and dilemmas. It concludes that parallel efforts should be undertaken - to implement the Principles and to negotiate an international treaty – in order to improve protection against an adverse impact of corporate operations on human rights. As for the Czech Republic, it is suggested to embark on the elaboration of the National Action Plan, thus providing for an opportunity to discuss implementation of the Principles among all the

  2. Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice.

    Science.gov (United States)

    Wolf, Leslie E; Patel, Mayank J; Williams Tarver, Brett A; Austin, Jeffrey L; Dame, Lauren A; Beskow, Laura M

    2015-01-01

    The federal Certificate of Confidentiality plays an important role in research on sensitive topics by authorizing researchers to refuse to disclose identifiable research data in response to subpoenas in any legal setting. However, there is little known about how effective Certificates are in practice. This article draws on our legal and empirical research on this topic to fill this information gap. It includes a description of the purpose of Certificates, their legislative and regulatory history, and a summary of the few reported and unreported cases that have dealt with Certificates. In addition, we outline other statutory confidentiality protections, compare them to the Certificate's protections, and analyze some of the vulnerabilities of a Certificate's protections. This analysis allows us to make specific recommendations for strengthening the protections afforded to research data. © 2015 American Society of Law, Medicine & Ethics, Inc.

  3. Protective effects of hesperidin against genotoxicity induced by {sup 99m}Tc-MIBI in human cultured lymphocyte cells

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinimehr, Seyed Jalal [Department of Radiopharmacy, Faculty of Pharmacy and Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences, Sari (Iran, Islamic Republic of)], E-mail: sjhosseinim@yahoo.com; Ahmadi, Amirhossein [Department of Radiopharmacy, Faculty of Pharmacy and Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences, Sari (Iran, Islamic Republic of); Beiki, Davood [Research Institute for Nuclear Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Habibi, Emran [Department of Radiopharmacy, Faculty of Pharmacy and Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences, Sari (Iran, Islamic Republic of); Mahmoudzadeh, Aziz [Laboratory of Cytogenetics, Novin Radiation Institute, Tehran (Iran, Islamic Republic of)

    2009-10-15

    Introduction: Radiopharmaceuticals have been widely used as nuclear tracers for myocardial perfusion imaging. The purpose of this study was to investigate the radioprotective effects of hesperidin as a flavonoid which protects against the genotoxic effects of {sup 99m}Tc-MIBI in human cultured lymphocytes. Methods: Whole blood samples from human volunteers were incubated with hesperidin at doses of 10, 50 and 100 {mu}mol. After 1 h of incubation, the lymphocytes were incubated with {sup 99m}Tc-MIBI (200 {mu}Ci/2 ml) for 3 h. The lymphocyte cultures were then mitogenically stimulated to allow for evaluation of the number of micronuclei in cytokinesis-blocked binucleated cells. Results: Incubation of lymphocytes with {sup 99m}Tc-MIBI at this high dose induces additional genotoxicity and shown by increases in micronuclei frequency in human lymphocytes. Hesperidin at these doses significantly reduced the micronuclei frequency in cultured lymphocytes. The maximum protective effect and greatest decrease in micronuclei frequency occurred when cultures were incubated with a 100-{mu}mol dose of 65% hesperidin. Conclusion: This study has important implications for patients undergoing nuclear medicine procedures. The results indicate a protective role for hesperidin against the genetic damage and side effects induced by radiopharmaceutical administration.

  4. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  5. Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.

    Science.gov (United States)

    Zhang, Qingwen; Wang, Qiong; Tian, Guang; Qi, Zhizhen; Zhang, Xuecan; Wu, Xiaohong; Qiu, Yefeng; Bi, Yujing; Yang, Xiaoyan; Xin, Youquan; He, Jian; Zhou, Jiyuan; Zeng, Lin; Yang, Ruifu; Wang, Xiaoyi

    2014-01-01

    Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge.

  6. Linking International Human Rights Law to Policy in Protecting against Adverse Effects of Climate Change

    National Research Council Canada - National Science Library

    Alkan Olsson, Ilhami; Alkan Olsson, Johanna

    2016-01-01

    The article aims to illustrate the multifaceted interlink between climate change, heat, and human rights and discuss in what ways international human rights law may be used to support the development...

  7. In Defense of Freedom: Protection of Human Rights at Home and Abroad

    Science.gov (United States)

    2010-10-01

    the Security Sector Beyond the OSCE Area: Regional Approaches in Africa an the Americas. Berlin: LIT-Verlag, 2007. Graff, Corinne, Carlos Pascual...Human Trafficking, Human Misery: The Global Trade in Human Beings. Santa Barbara: Praeger Security International, 2009. (HQ 281 .A76 2009) Cullen ...Asians View Democracy. New York: Columbia UP, 2008. (JQ 1499 .A91 H69 2008) Cullen -DuPont, Kathryn. Human Trafficking. Global Issues. New York

  8. Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans

    DEFF Research Database (Denmark)

    Maiani, Giuseppe; Castón, María Jesús Periago; Catasta, Giovina

    2009-01-01

    Carotenoids are one of the major food micronutrients in human diets and the overall objective of this review is to re-examine the role of carotenoids in human nutrition. We have emphasized the attention on the following carotenoids present in food and human tissues: -carotene, -cryptoxanthin, -ca...

  9. Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.

    LENUS (Irish Health Repository)

    Seymour, C B

    2003-11-17

    l-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.

  10. Antibody-secreting cell responses and protective immunity assessed in gnotobiotic pigs inoculated orally or intramuscularly with inactivated human rotavirus.

    Science.gov (United States)

    Yuan, L; Kang, S Y; Ward, L A; To, T L; Saif, L J

    1998-01-01

    Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075-3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.

  11. Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques.

    Science.gov (United States)

    Moldt, Brian; Le, Khoa M; Carnathan, Diane G; Whitney, James B; Schultz, Niccole; Lewis, Mark G; Borducchi, Erica N; Smith, Kaitlin M; Mackel, Joseph J; Sweat, Shelby L; Hodges, Andrew P; Godzik, Adam; Parren, Paul W H I; Silvestri, Guido; Barouch, Dan H; Burton, Dennis R

    2016-06-19

    Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126. Animals were administered PGT126 at three different doses before challenged either vaginally or rectally with a single dose of SHIVSF163P3. Viral loads, PGT126 serum concentrations, and serum neutralizing titers were monitored. In vaginally challenged animals, sterilizing immunity was achieved in all animals administered 10 mg/kg, in two of five animals administered 2 mg/kg and in one of five animals administered 0.4 mg/kg PGT126. Comparable protection was observed for the corresponding groups challenged rectally as sterilizing immunity was achieved in three of four animals administered 10 mg/kg, in two of four animals administered 2 mg/kg and in none of four animals administered 0.4 mg/kg PGT126. Serological analysis showed similar serum concentrations of PGT126 and serum neutralization titers in animals administered the same antibody dose. Our data suggest that broadly neutralizing antibody-mediated protection is not strongly dependent on the mucosal route of challenge, which indicates that a vaccine aimed to induce a neutralizing antibody response would have broadly similar efficacy against both primary transmission routes for HIV.

  12. DNA-protective effects of sumach (Rhus coriaria L.), a common spice: Results of human and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Asima; Ferk, Franziska; Simic, Tatjana [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Brantner, Adelheid [Institute of Pharmacognosy, University of Graz, Universitaetsplatz 4/I, A-8010 Graz (Austria); Dusinska, Maria [Center for Ecological Economics, Norwegian Institute for Air Research, Instituttveien 18, NO-2027 Kjeller (Norway); Kundi, Michael [Institute of Environmental Health, Center for Public Health, Medical Unviversity of Vienna (Austria); Hoelzl, Christine; Nersesyan, Armen [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Knasmueller, Siegfried [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)], E-mail: siegfried.knasmueller@meduniwien.ac.at

    2009-02-10

    Sumach (Rhus coriaria L.) is widely used as a spice. The aim of this study was the investigation of its DNA-protective effects in humans and animals. Prevention of the formation of strand breaks and oxidized DNA bases as well as the protection against H{sub 2}O{sub 2}- and ({+-})-anti-benzo[a]pyrene-7,8-dihydro-diol-9,10-epoxide (BPDE)-induced DNA-damage were monitored in human lymphocytes in a placebo controlled trial (N = 8/group) with ethanolic extract of sumach (3.0 g/day, 3 days) in single cell gel electrophoresis assays. Furthermore, DNA-protective effects of sumach were monitored in different inner organs of rats under identical conditions. No alteration of DNA-migration was detectable in human lymphocytes under standard conditions, but a decrease of the tail-lengths due to formation of oxidized purines and pyrimidines (52% and 36%) was found with lesion-specific enzymes. Also damage caused by H{sub 2}O{sub 2} and BPDE was significantly reduced by 30% and 69%, respectively. The later effect may be due to induction of glutathione S-transferase (GST). After the intervention, the overall GST (CDNB) activity in plasma was increased by 40%, GST-{alpha} by 52% and GST-{pi} by 26% (ELISA). The antioxidant effects of extract are probably due to scavenging which was observed in in vitro experiments, which also indicated that gallic acid is the active principle of sumach. The animal experiments showed that sumach also causes protection in inner organs. Supplementation of the drinking water (0.02 g/kg per animal) decreased the formation of oxidized DNA bases in colon, liver, lung and lymphocytes; also after {gamma}-irradiation pronounced effects were seen.

  13. Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans.

    Science.gov (United States)

    Fresnay, Stephanie; McArthur, Monica A; Magder, Laurence; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2016-03-01

    Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. Typhi), is a major public health problem worldwide. Development of novel vaccines remains imperative, but is hampered by an incomplete understanding of the immune responses that correlate with protection. Recently, a controlled human infection model was re-established in which volunteers received ~10(3) cfu wild-type S. Typhi (Quailes strain) orally. Twenty-one volunteers were evaluated for their cell-mediated immune (CMI) responses. Ex vivo PBMC isolated before and up to 1 year after challenge were exposed to three S. Typhi-infected targets, i.e., autologous B lymphoblastoid cell-lines (B-LCL), autologous blasts and HLA-E restricted AEH B-LCL cells. CMI responses were evaluated using 14-color multiparametric flow cytometry to detect simultaneously five intracellular cytokines/chemokines (i.e., IL-17A, IL-2, IFN-g, TNF-a and MIP-1b) and a marker of degranulation/cytotoxic activity (CD107a). Herein we provide the first evidence that S. Typhi-specific CD8+ responses correlate with clinical outcome in humans challenged with wild-type S. Typhi. Higher multifunctional S. Typhi-specific CD8+ baseline responses were associated with protection against typhoid and delayed disease onset. Moreover, following challenge, development of typhoid fever was accompanied by decreases in circulating S. Typhi-specific CD8+ T effector/memory (TEM) with gut homing potential, suggesting migration to the site(s) of infection. In contrast, protection against disease was associated with low or no changes in circulating S. Typhi-specific TEM. These studies provide novel insights into the protective immune responses against typhoid disease that will aid in selection and development of new vaccine candidates.

  14. Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model.

    Science.gov (United States)

    Dunachie, Susanna; Berthoud, Tamara; Hill, Adrian V S; Fletcher, Helen A

    2015-09-29

    The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. These results represent novel insights into the immune repertoires involved in malaria vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Can human rights standards help protect children and youth from the detrimental impact of alcohol beverage marketing and promotional activities?

    Science.gov (United States)

    Chapman, Audrey R

    2017-01-01

    The alcohol industry in the Latin American and Caribbean (LAC) region promotes demand for alcohol products actively through a number of channels, including advertising and sponsorship of sports and other events. This paper evaluates whether human rights instruments that Latin American countries have ratified can be used to limit children's exposure to alcohol advertising and promotion. A review was conducted of the text of, and interpretative documents related to, a series of international and regional human rights instruments ratified by most countries in the LAC region that enumerate the right to health. The Convention on the Rights of the Child has the most relevant provisions to protect children and youth from alcohol promotion and advertising. Related interpretive documents by the United Nations Committee on the Rights of the Child affirm that corporations hold duties to respect and protect children's right to health. Human rights norms and law can be used to regulate or eliminate alcohol beverage marketing and promotional activities in the Latin American region. The paper recommends developing a human rights based Framework Convention on Alcohol Control to provide guidance. © 2016 Society for the Study of Addiction.

  16. N-acetylcysteine protects against bupivacaine-induced myotoxicity caused by oxidative and sarcoplasmic reticulum stress in human skeletal myotubes.

    Science.gov (United States)

    Galbes, Olivier; Bourret, Annick; Nouette-Gaulain, Karine; Pillard, Fabien; Matecki, Stefan; Py, Guillaume; Mercier, Jacques; Capdevila, Xavier; Philips, Alexandre

    2010-09-01

    Local anesthetics offer the benefits of extended analgesia with greater patient satisfaction and faster rehabilitation compared with intravenous morphine. These benefits, however, can be offset by adverse iatrogenic muscle pain. Here, the authors investigate the mechanisms of local anesthetic-induced myotoxicity and assess the protective effect of N-acetylcysteine. The authors used primary cell cultures of human skeletal muscle myoblasts to study local anesthetic adverse effects. Production of reactive oxygen species was investigated in human skeletal myotubes by fluorescence microscopy. Expression of sarcoplasmic/endoplasmic reticulum stress markers and induction of apoptosis were followed by immunofluorescence and Western blot analysis. Finally, the effect of N-acetylcysteine on bupivacaine-induced myotoxicity was investigated in vitro. Bupivacaine sequentially induced reactive oxygen species production, oxidative stress, sarcoplasmic/endoplasmic reticulum stress, and activation of caspases 9 and 7 in human differentiated myoblasts. These iatrogenic effects were prevented by N-acetylcysteine. The authors demonstrated a protective effect of N-acetylcysteine against bupivacaine-induced sarcoplasmic/endoplasmic reticulum stress and apoptosis in primary human skeletal muscle cell.

  17. Lack of homologous protection against Campylobacter jejuni CG8421 in a human challenge model.

    Science.gov (United States)

    Kirkpatrick, Beth D; Lyon, Caroline E; Porter, Chad K; Maue, Alex C; Guerry, Patricia; Pierce, Kristen K; Carmolli, Marya P; Riddle, Mark S; Larsson, Catherine J; Hawk, Douglas; Dill, Elizabeth A; Fingar, A; Poly, Frederic; Fimlaid, Kelly A; Hoq, Fahmida; Tribble, David R

    2013-10-01

    Campylobacter jejuni is a common cause of diarrhea and is associated with serious postinfectious sequelae. Although symptomatic and asymptomatic infections are recognized, protective immunity is not well understood. Previous data suggests that interferon γ (IFN-γ) may be associated with protection. To better define the clinical and immunologic development of protective immunity to C. jejuni, we assessed the ability of an initial infection to prevent clinical illness after a second experimental infection. Subjects with no clinical or immunologic evidence of prior infection with C. jejuni received an initial challenge with C. jejuni CG8421 with rechallenge 3 months later. The primary endpoint was campylobacteriosis, as defined by diarrhea and/or systemic signs. Close inpatient monitoring was performed. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG), fecal IgA, IgA antibody-secreting cells (ASCs), and IFN-γ production were evaluated. All subjects were treated with antibiotics and were clinically well at discharge. Fifteen subjects underwent a primary infection with C. jejuni CG8421; 14 (93.3%) experienced campylobacteriosis. Eight subjects received the second challenge, and all experienced campylobacteriosis with similar severity. Immune responses after primary infection included serum IgA, IgG, ASC, and IFN-γ production. Responses were less robust after secondary infection. In naive healthy adults, a single infection with CG8421 did not protect against campylobacteriosis. Although protection has been demonstrated with other strains and after continuous environmental exposure, our work highlights the importance of prior immunity, repeated exposures, and strain differences in protective immunity to C. jejuni. NCT01048112.

  18. Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model

    Science.gov (United States)

    Kirkpatrick, Beth D.; Lyon, Caroline E.; Porter, Chad K.; Maue, Alex C.; Guerry, Patricia; Pierce, Kristen K.; Carmolli, Marya P.; Riddle, Mark S.; Larsson, Catherine J.; Hawk, Douglas; Dill, Elizabeth A.; Fingar, A.; Poly, Frederic; Fimlaid, Kelly A.; Hoq, Fahmida; Tribble, David R.

    2013-01-01

    Background. Campylobacter jejuni is a common cause of diarrhea and is associated with serious postinfectious sequelae. Although symptomatic and asymptomatic infections are recognized, protective immunity is not well understood. Previous data suggests that interferon γ (IFN-γ) may be associated with protection. To better define the clinical and immunologic development of protective immunity to C. jejuni, we assessed the ability of an initial infection to prevent clinical illness after a second experimental infection. Methods. Subjects with no clinical or immunologic evidence of prior infection with C. jejuni received an initial challenge with C. jejuni CG8421 with rechallenge 3 months later. The primary endpoint was campylobacteriosis, as defined by diarrhea and/or systemic signs. Close inpatient monitoring was performed. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG), fecal IgA, IgA antibody-secreting cells (ASCs), and IFN-γ production were evaluated. All subjects were treated with antibiotics and were clinically well at discharge. Results. Fifteen subjects underwent a primary infection with C. jejuni CG8421; 14 (93.3%) experienced campylobacteriosis. Eight subjects received the second challenge, and all experienced campylobacteriosis with similar severity. Immune responses after primary infection included serum IgA, IgG, ASC, and IFN-γ production. Responses were less robust after secondary infection. Conclusions. In naive healthy adults, a single infection with CG8421 did not protect against campylobacteriosis. Although protection has been demonstrated with other strains and after continuous environmental exposure, our work highlights the importance of prior immunity, repeated exposures, and strain differences in protective immunity to C. jejuni. Clinical Trials Registration. NCT01048112 PMID:23840001

  19. Building Prevention to Protect: The Inter-American Human Rights System

    Directory of Open Access Journals (Sweden)

    Carlos Portales

    2017-03-01

    Full Text Available The article explores the way that the Inter-American human rights system assumes the “responsibility to protect” in the context of serious violations of human rights that can be characterized as war crimes, crimes against humanity, genocide, and ethnic cleansing. The essay describes  how the Inter-American Commission on Human Rights and the Inter-American Court of Human Rights have responded to such situations by using the ample powers granted to them by the OAS member states. The authors consider that these organs have been some of the most effective tools with which this region has confronted such situations by seeking system has contributed to building democratic regimes in the majority of the countries of the hemisphere. This has been crucial to avoiding serious violations of human rights such as those mentioned above, which would have required urgent international intervention to overcome.

  20. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    Science.gov (United States)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  1. Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species.

    Directory of Open Access Journals (Sweden)

    Christian Mitri

    2009-09-01

    Full Text Available Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island (PRI of the A. gambiae genome. The APL1 family of leucine-rich repeat (LRR proteins was highlighted by candidate gene studies in the PRI, and is comprised of paralogs APL1A, APL1B and APL1C that share > or =50% amino acid identity. Here, we present a functional analysis of the joint response of APL1 family members during mosquito infection with human and rodent Plasmodium species. Only paralog APL1A protected A. gambiae against infection with the human malaria parasite P. falciparum from both the field population and in vitro culture. In contrast, only paralog APL1C protected against the rodent malaria parasites P. berghei and P. yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2 pathway, while protection against P. berghei infection was shown to require Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2-F isoform of Rel2 confers protection against P. falciparum. Protection correlates with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting that the Rel2-S anti-parasite phenotype results at least in part from its transcriptional control over APL1A. These results indicate that distinct members of the APL1 gene family display a mutually exclusive protective effect against different classes of Plasmodium parasites. It appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. It is known that insect innate immune pathways can distinguish between grossly different microbes such as Gram-positive bacteria, Gram-negative bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between

  2. Vulnerability and the Principle of Non-refoulement in the European Court of Human Rights : Towards an Increased Scope of Protection for Persons Fleeing from Extreme Poverty?

    NARCIS (Netherlands)

    Flegar, Veronika

    2016-01-01

    “Economic refugees” largely remain outside the international protection regimes of refugee and human rights law. Nevertheless, recent case law of the European Court of Human Rights (ECtHR) opens up limited possibilities for economic refugees to rely on Article 3 of the European Convention on Human

  3. Can "extreme poverty" protect against refoulement? : Economic refugees in the light of recent case law of the European Court of Human Rights

    NARCIS (Netherlands)

    Flegar, Veronika

    2015-01-01

    “Economic refugees” largely remain outside the international protection regimes of refugee and human rights law. Nevertheless, recent case law of the European Court of Human Rights (ECtHR) opens up limited possibilities for economic refugees to rely on Article 3 of the European Convention on Human

  4. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour.

    Science.gov (United States)

    Herd, Karen A; Harvey, Tracey; Khromykh, Alexander A; Tindle, Robert W

    2004-02-20

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses.

  5. Protective effect of Opuntia ficus-indica L. cladodes against UVA-induced oxidative stress in normal human keratinocytes.

    Science.gov (United States)

    Petruk, Ganna; Di Lorenzo, Flaviana; Imbimbo, Paola; Silipo, Alba; Bonina, Andrea; Rizza, Luisa; Piccoli, Renata; Monti, Daria Maria; Lanzetta, Rosa

    2017-12-15

    Opuntia ficus-indica L. is known for its beneficial effects on human health, but still little is known on cladodes as a potent source of antioxidants. Here, a direct, economic and safe method was set up to obtain water extracts from Opuntia ficus-indica cladodes rich in antioxidant compounds. When human keratinocytes were pre-treated with the extract before being exposed to UVA radiations, a clear protective effect against UVA-induced stress was evidenced, as indicated by the inhibition of stress-induced processes, such as free radicals production, lipid peroxidation and GSH depletion. Moreover, a clear protective effect against apoptosis in pre-treated irradiated cells was evidenced. We found that eucomic and piscidic acids were responsible for the anti-oxidative stress action of cladode extract. In conclusion, a bioactive, safe, low-cost and high value-added extract from Opuntia cladodes was obtained to be used for skin health/protection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Doxycycline protects human intestinal cells from hypoxia/reoxygenation injury: Implications from an in-vitro hypoxia model.

    Science.gov (United States)

    Hummitzsch, Lars; Zitta, Karina; Berndt, Rouven; Kott, Matthias; Schildhauer, Christin; Parczany, Kerstin; Steinfath, Markus; Albrecht, Martin

    2017-04-15

    Intestinal ischemia/reperfusion (I/R) injury is a grave clinical emergency and associated with high morbidity and mortality rates. Based on the complex underlying mechanisms, a multimodal pharmacological approach seems necessary to prevent intestinal I/R injury. The antibiotic drug doxycycline, which exhibits a wide range of pleiotropic therapeutic properties, might be a promising candidate for also reducing I/R injury in the intestine. To investigate possible protective effects of doxycycline on intestinal I/R injury, human intestinal CaCo-2 cells were exposed to doxycycline at clinically relevant concentrations. In order to mimic I/R injury, CaCo-2 were thereafter subjected to hypoxia/reoxygenation by using our recently described two-enzyme in-vitro hypoxia model. Investigations of cell morphology, cell damage, apoptosis and hydrogen peroxide formation were performed 24h after the hypoxic insult. Hypoxia/reoxygenation injury resulted in morphological signs of cell damage, elevated LDH concentrations in the respective culture media (Pdoxycycline (5µM, 10µM, 50µM) reduced the hypoxia induced signs of cell damage and LDH release (Pdoxycycline protects human intestinal cells from hypoxia/reoxygenation injury in-vitro. Further animal and clinical studies are required to prove the protective potential of doxycycline on intestinal I/R injury under in-vivo conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The evaluation of protective effect of lycopene against genotoxic influence of X-irradiation in human blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Gajowik, Aneta; Dobrzynska, Malgorzata M. [National Institute of Public Health-National Institute of Hygiene, Department of Radiation Protection and Radiobiology, Warsaw (Poland)

    2017-11-15

    Many studies suggest that exogenous antioxidants may protect cells against DNA damage caused with ionizing radiation. One of the most powerful antioxidants is lycopene (LYC), a carotenoid derived from tomatoes. The aim of this study was to investigate, using the comet assay, whether LYC can act as protectors/modifiers and prevent DNA damage induced in human blood lymphocytes, as well as to mitigate the effects of radiation exposure. In this project, LYC, dissolved in DMSO at a concentration of 10, 20 or 40 μM/ml of cell suspension, was added to the isolated lymphocytes from human blood at appropriate intervals before or after the X-irradiation at doses of 0.5, 1 and 2 Gy. Cell viability in all groups was maintained at above 70%. The results showed the decrease of DNA damage in cells treated with various concentrations of LYC directly and 1 h before exposure to X-rays compared to the control group exposed to irradiation alone. Contrary results were observed in cells exposed to LYC immediately after exposure to ionizing radiation. The studies confirmed the protective effect of LYC against DNA damage induced by ionizing radiation, but after irradiation the carotenoid did not stimulate of DNA repair and cannot act as modifier. However, supplementation with LYC, especially at lower doses, may be useful in protection from radiation-induced oxidative damage. (orig.)

  8. Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?

    Science.gov (United States)

    Qi, Miao; Abdelatti, Mahmoud; Krilis, Matthew; Madigan, Michele C; Weaver, James; Guymer, Robyn H; McCluskey, Peter; Wang, Ying; Zhou, Saijun; Krilis, Steven A; Giannakopoulos, Bill

    2016-01-01

    Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (β2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of β2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate β2GPI in the retina and choroid of patients with AMD. Free thiol β2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of β2GPI and free thiol bovine serum albumin were not protective. Free thiol β2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol β2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.

  9. The right to life and criminal-law protection of the human person in the Western Balkans

    Directory of Open Access Journals (Sweden)

    Etlon Peppo

    2015-07-01

    Full Text Available The basic principle for which a democratic governance stands, are expressed in the “Declaration of Independence of the United States of America with the words of Thomas Jefferson: “We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights that among these are Life, Liberty and the Pursuit of Happiness. That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed” The government of a democratic state does not exist to recognize the basic human rights, but to respect and guarantee the protection of these rights that any person possesses and benefits due to his existence starting from the most important right: The right to life, which is faced against the duty of the state for the protection of the human person’s life! In this sense this article analyzes the criminal-law protection of life in the Western Balkans.

  10. Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses.

    Science.gov (United States)

    Carney, Daniel W; Nelson, Christian D S; Ferris, Bennett D; Stevens, Julia P; Lipovsky, Alex; Kazakov, Teymur; DiMaio, Daniel; Atwood, Walter J; Sello, Jason K

    2014-09-01

    Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats.

    Science.gov (United States)

    Widjojoatmodjo, Myra N; Boes, Jolande; van Bers, Marleen; van Remmerden, Yvonne; Roholl, Paul J M; Luytjes, Willem

    2010-06-02

    Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (DeltaG) were constructed based on a clinical RSV isolate (strain 98-25147-X). Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for DeltaG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Collectively, the data indicate that a single dose immunization with the highly attenuated DeltaG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since DeltaG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  12. Cinnamaldehyde protects human dental pulp cells against oxidative stress through the Nrf2/HO-1-dependent antioxidant response.

    Science.gov (United States)

    Kim, Nam-Yi; Ahn, Sang-Gun; Kim, Soo-A

    2017-11-15

    Cinnamaldehyde (CA) has various functional properties, such as anti-cancer, anti-microbial, anti-inflammatory, and anti-oxidant activities. This study examined the intracellular signaling mechanisms of CA on the oxidative stress response in human dental pulp cells (hDPCs). The results showed that CA did not have any cell cytotoxicity or cause morphological changes at concentrations up to 50µM. A CA treatment strongly up-regulated the cellular protein level of heme oxygenase-1 (HO-1) and promoted Nrf2 translocation to the nucleus. CA-mediated Nrf2/HO-1 activation reduced the level of reactive oxygen species and protected the hDPCs from H2O2-induced oxidative stress, which induces apoptosis. Moreover, HO-1 depletion by siRNA attenuated the CA-mediated cell protection against oxidative stress. These results indicate that CA protects hDPCs dysfunction under oxidative stress conditions, and this effect is mediated by Nrf2 activation and the up-regulation of HO-1. Overall, these observations suggest that CA is a potential therapeutic agent for cell protection against oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Human poly- and cross-reactive anti-viral antibodies and their impact on protection and pathology.

    Science.gov (United States)

    Warter, Lucile; Appanna, Ramapraba; Fink, Katja

    2012-09-01

    Anti-viral immune responses have been studied extensively in order to inform rational vaccine design. Following viral infection, the balance of pathologic and protective antibody responses in the host can critically influence clinical outcomes. Comparisons of the different classes of antibodies produced after acute or chronic viral infections have uncovered common features of anti-viral responses, but these analyses have also revealed temporal differences in neutralizing antibody production, variable neutralization potency and differential induction of cross-reactive antibodies. Cross-reactive antibodies are known to play crucial protective roles in host responses to chronic viral infections; recent studies in human immunodeficiency virus long-term controllers have identified a novel class of broadly neutralizing antibodies generated from highly mutated and selected memory B cells. Here, we summarize the various roles played by cross- and poly-reactive antibodies in acute and persistent viral infections, with a focus on the potential contribution of these antibodies to dengue virus (DENV) immunopathology and host protection. Since host antibodies profoundly alter the course of viral infections, effective DENV vaccine design will require a better understanding of the origin, affinity maturation and protective potential of the poly-reactive and cross-reactive antibodies induced by different interventions.

  14. Protective effects of 7-difluoromethyl-5,4'-dimethoxygenistein against human aorta endothelial injury caused by lysophosphatidyl choline.

    Science.gov (United States)

    Liu, Fei; Cao, Jian-Guo; Li, Cheng; Tan, Jin-Seng; Fu, Xiao-Hua

    2012-04-01

    7-Difluoromethyl-5,4'-dimethoxygenistein (DFMG) is an active new derivative of genistein (GEN). It has shown effective protection in vascular endothelial injury. To further investigate its potential protective effects and its mechanism probably related to atherosclerosis, in present study, human aorta endothelial cells (HAECs) were chosen and treated with various concentrations of lysophosphatidyl choline (LPC) to establish an experimental model. Results showed that 10.0 μmol/l of LPC was optimal for inducing HAEC injury. DFMG pretreatment was able to prevent HAEC injury induced by LPC and restore cell viability in a concentration-dependent manner. The protective efficacy of DFMG (10.0 μmol/l) was significantly greater than that of GEN (10.0 μmol/l) and vitamin E (50.0 μmol/l). The mechanisms underlying the protective effects of DFMG are related to the activation of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase and to the clearance of intracellular reactive oxygen species. DFMG inhibits the apoptosis of HAECs mediated by LPC involving the blockage of the mitochondrial apoptotic pathway.

  15. After Life Esidimeni: True human rights protections or lip service to ...

    African Journals Online (AJOL)

    2017-06-03

    Jun 3, 2017 ... South Africa (SA)'s Constitution,[1] in its preamble, affirms that it was adopted to, inter alia, 'lay the foundations for a democratic and open society in which government is based on the will of the people and every citizen is equally protected by law', and 'improve the quality of life of all citizens and free the ...

  16. Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Yafan Yang

    2015-01-01

    Full Text Available Ultraviolet (UV irradiation causes damage in skin by generating excessive reactive oxygen species (ROS and induction of matrix metalloproteinases (MMPs, leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption.

  17. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference ...

  18. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  19. Human performance decrements associated with the bandwidth of laser protective eyewear concepts

    Science.gov (United States)

    Molchany, Jerome W.; Lund, David J.

    1996-04-01

    Protecting the eye from coherent light sources is of critical concern to both military and civilian laser users. Laser protective eyewear degrades visual performance. Common and emerging applications use lasers emitting at numerous wavelengths or single lasers emitting at multiple wavelengths. Protection against multiple wavelengths increases the difficulty in selecting or building protective eyewear and concomitantly usually increases the performance penalty. Pursuit tracking performance decrements were measured as a function of bandwidth and peak wavelength transmission for 12 bandpass filters. Eight volunteers tracked a target subtending 34 milliradians (mrad) at a constant velocity of 5 mrad/sec for 15 sec. The target traversed an arc located 5 m from the tracker. Each volunteer received two training days and two test days. Twelve bandpass filters, with bandwidths of 10, 25, 40, and 70 nm, and peak wavelengths of 450, 550, and 650 nm were randomly inserted into the optics of the tracker. No volunteer received all 4 bandwidths of one peak wavelength on either test day, thereby reducing any adaptational effect. Luminance was equated across filters using Neutral Density (ND) filters. An ND filter of equal Optical Density served as the control. The total luminance at the eye was 0.8 cd/m2. Trials were collected at a rate of 4 per filter. The 10 nm blue filter elicited the poorest performance, followed by the 25, 40, and 70 nm blue filters. The red filters enhanced performance across all but the narrowest bandwidth. It can be assumed that the blue end of the visible spectrum with it's `forward of the retina' focusing properties and the low number of blue photoreceptors are responsible for the large decrements. Current philosophy in laser eye protection is to allow as much of the blue end of the spectrum through a filter to preserve scotopic transmission. The shortwave transmission may inadvertently increase error rates for visual tasks.

  20. Protecting the Teaching and Learning Environment: A Hybrid Model for Human Subject Research Public Policy Implementation

    Science.gov (United States)

    Hottenstein, Kristi N.

    2017-01-01

    Regulations for research involving human subjects have long been a critical issue in higher education. Federal public policy for research involving human subjects impacts institutions of higher education by requiring all federally funded research to be passed by an Institutional Review Board (IRB). Undergraduate research is no exception. Given the…

  1. The Mass Media: Veritable Tool in the Protection of Human Rights ...

    African Journals Online (AJOL)

    Furthermore, the study proposes a guide-dog approach of journalism to Human Rights issues, problems and challenges, as well as the Development Media Theory and Agenda- Setting Theory of Mass Communication to the devastating effects of the violation and the discouragement of Human Rights in Nigeria. The paper ...

  2. Human IL-32 expression protects mice against a hypervirulent strain of Mycobacterium tuberculosis

    NARCIS (Netherlands)

    Bai, X.; Shang, S.; Henao-Tamayo, M.; Basaraba, R.J.; Ovrutsky, A.R.; Matsuda, J.L.; Takeda, K.; Chan, M.M.; Dakhama, A.; Kinney, W.H.; Trostel, J.; Bai, A.; Honda, J.R.; Achcar, R.; Hartney, J.; Joosten, L.A.B.; Kim, S.H.; Orme, I.; Dinarello, C.A.; Ordway, D.J.; Chan, E.D.

    2015-01-01

    Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of Mycobacterium tuberculosis (MTB) but the role of IL-32 in vivo against MTB remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human IL-32gamma

  3. Ouabain Protects Human Renal Cells against the Cytotoxic Effects of Shiga Toxin Type 2 and Subtilase Cytotoxin

    Directory of Open Access Journals (Sweden)

    María M. Amaral

    2017-07-01

    Full Text Available Hemolytic uremic syndrome (HUS is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx-producing Escherichia coli (STEC. In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2 are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans. Considering that Ouabain (OUA may prevent the apoptosis process, in this study we evaluated if OUA is able to avoid the damage caused by Stx2 and SubAB on human glomerular endothelial cells (HGEC and the human proximal tubule epithelial cell (HK-2 line. HGEC and HK-2 were pretreated with OUA and then incubated with the toxins. OUA protected the HGEC viability from Stx2 and SubAB cytotoxic effects, and also prevented the HK-2 viability from Stx2 effects. The protective action of OUA on HGEC and HK-2 was associated with a decrease in apoptosis and an increase in cell proliferation. Our data provide evidence that OUA could be considered as a therapeutic strategy to avoid the renal damage that precedes HUS.

  4. Protection of human subjects of biomedical research in the United States. A contrast with recent experience in the United Kingdom.

    Science.gov (United States)

    Levine, R J

    1988-01-01

    In the U.S., the development of extensive regulations for the protection of human subjects of research began in the 1960s and continued through the 1970s. The substance of these regulations reflects the American social and political climate of the time. There is a focus on rights--e.g., to be left alone, to be self-determining--reflected in elaborate requirements to assure the validity and documentation of informed consent. There is also a focus on systems of disinterested review and monitoring procedures to assure uniform adherence to the requirements of the regulations. To the extent that the U.S. has developed extensive regulations in this field, it may be viewed as more advanced than the U.K. And yet, it is apparent that there remain on both sides of the Atlantic very difficult and similar problems regarding the definition of responsible research. Such problems are illustrated by consideration of current controversies about the ethical justification of RCTs. There are some features of the U.S. regulatory system that I can commend to the attention of other nations as they develop policies for the protection of human research subjects. For example, a uniform requirement for informed consent and committee review appears to be responsive to some problems currently encountered in the conduct of RCTs in the U.K. A note of caution is in order, however. Some features of our regulatory policy and practices are excessively inflexible, wasteful of human resources, and occasionally counterproductive.

  5. Conservation outside protected areas and the effect of human-dominated landscapes on stress hormones in Savannah elephants.

    Science.gov (United States)

    Ahlering, M A; Maldonado, J E; Eggert, L S; Fleischer, R C; Western, D; Brown, J L

    2013-06-01

    Biodiversity conservation strategies are increasingly focused on regions outside national protected areas, where animals face numerous anthropogenic threats and must coexist with human settlements, livestock, and agriculture. The effects of these potential threats are not always clear, but they could have profound implications for population viability. We used savannah elephants (Loxodonta africana) as a case study to assess the physiological stress associated with living in a human-livestock-dominated landscape. We collected samples over two 3-month periods in 2007 and 2008. We used fecal DNA to identify 96 individual elephants in a community conservation area (CCA) and measured fecal glucocorticoid metabolite (FGM) concentrations as a proxy for stress. The CCA is community Maasai land managed for livestock and wildlife. We compared the FGM concentrations from the CCA to FGM concentrations of 40 elephants in Amboseli National Park and 32 elephants in the Maasai Mara National Reserve, where human settlements and intense livestock grazing were absent. In the CCA, we found no significant individual differences in FGM concentrations among the elephants in 2007 (p = 0.312) or 2008 (p = 0.412) and no difference between years (p = 0.616). The elephants in the CCA had similar FGM concentrations to the Maasai Mara population, but Amboseli elephants had significantly lower FGM concentrations than those in either Maasai Mara or the CCA (Tukey pairwise test, p elephants living on CCA communal land, which is encouraging for conservation strategies promoting the protection of animals living outside protected areas. Conservation Biology © 2013 Society for Conservation Biology No claim to original US government works.

  6. Human-related factors regulate the presence of domestic dogs in protected areas

    OpenAIRE

    Soto Navarro, Carolina; Palomares, Francisco

    2015-01-01

    Copyright © Fauna & Flora International 2014. The presence of domestic species such as dogs Canis familiaris in protected areas can cause problems for native species as a result of competition, predation and disease transmission. To improve our ability to design effective control policies we investigated the factors affecting detection of dog tracks in a Mediterranean national park. We investigated the presence of dogs across 69 2 × 2 km grid squares in Doñana National Park in south-west Spai...

  7. Genetics, data protection and non-discrimination: some reflections from an international human rights law perspective.

    Science.gov (United States)

    Hendriks, A C

    2001-01-01

    As a result of progress in medical research genetic traits can increasingly be used as predictive factors and selection criteria. This calls into question the appropriateness, validity and legitimacy of genetic traits as (co-)determinants in decision-making processes. This paper confines itself to examining the implications of genetics on the right to privacy--notably data protection--and the right not to be discriminated against.

  8. The fight against trafficking in human beings in EU: promoting legal cooperation and victims' protection [booklet

    OpenAIRE

    Equipo de trabajo del Proyecto THB:COOPtoFight

    2014-01-01

    With the financial support from the Prevention of and Fight against Crime Programme of the European Union | European Commission - Directorate-General Home Affairs. CooptoFight: Research Context and Objectives | Brief Glossary on THB | The Legal Key-stages of THB Fighting and Victims’ Protection | Brief Conclusions | Links to access to the International and European Legal Framework and so-me important Institutional Recommendations on THB | References

  9. How Does Iranian's Legal System Protect Human Vulnerability and Personal Integrity in Medical Research?

    OpenAIRE

    Karoubi, Mohammad Taghi; Akhondi, Mohammad Mehdi

    2011-01-01

    The astonishing advance of medical science in recent decades has had endless advantages for humans, including improved level of health, prevention of disease and advances in treatment. These advances depend to a great extent on conducting continuous research. However, besides its enormous advantages, the sole interest of medical science undermines the principles of respect for human vulnerability and personal integrity, in both positive and negative approaches. The positive approach refers to...

  10. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning

    OpenAIRE

    Huang, Yue-Jin; Huang, Yue; Baldassarre, Hernan; Wang, Bin; Lazaris, Anthoula; Leduc, Martin; Bilodeau, Annie S; Bellemare, Annie; Côté, Mélanie; Herskovits, Peter; Touati, Madjid; Turcotte, Carl; Valeanu, Loredana; Lemée, Nicolas; Wilgus, Harvey

    2007-01-01

    Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats w...

  11. International Protection of Conscientious Objection: A Comparative Analysis of Human Rights Systems and Perspectives of the Inter- American System

    Directory of Open Access Journals (Sweden)

    María Carmelina Londoño Lázaro

    2016-01-01

    Full Text Available In this article, the recognition of conscientious objection in three international systems for the protection of human rights is analyzed: the Inter-American system, the European system and the United Nations system. The comparative system which is adopted allows for notifications as to common developments, the failings and some tensions which have been confronted by international organs in controversial cases. From this analysis are drawn some lessons which may serve for the guardianship of this law in the Inter- American system.

  12. Triterpenoid α-amyrin stimulates proliferation of human keratinocytes but does not protect them against UVB damage

    DEFF Research Database (Denmark)

    Biskup, Edyta; Gołębiowski, Marek; Gniadecki, Robert

    2012-01-01

    CaT) by about 18% while other extract components were ineffective. A panel of biochemical and cell-based assays testing the antioxidative and cytoprotective activites of α-amyrin indicated no antioxidative activity of this compound. α-Amyrin did not protect HaCaT cells against the damage caused by UVB radiation.......Rhaponticum carthamoides plants ("maral root") are widely used in Siberian folk medicine. The present study reports for the first time the presence of pentacyclic terpenoid, α-amyrin, in methanol extract from leaves of this plant. α-Amyrin induced proliferation of human keratinocytes (Ha...

  13. [Protective effect of Salidroside on oxidative damage to human lens epithelial cells].

    Science.gov (United States)

    Zhu, Fengmei; Zheng, Guangying; Zheng, Yan; Zhang, Meng

    2015-02-01

    The aim of the experiment was to investigate the effects of salidroside (Sal) on oxidative damage to human lens epithelial cells (HLEC). Experimental study. The cultured HLECwas intervened with hydrogen peroxide (H2O2) which created oxidative damage model to observe the effect of Sal on HLECs. The cultured cells during the logarithmic phase were interposed by different concentrations Sal (0 µmol/L, 10 µmol/L, 30 µmol/L, 50 µmol/L, 100 µmol/L, 200 µmol/L) for 24 h. Then the viability of cells was detected by cell counting Kit-8 (CCK-8) assay. The cells were divided into 5 groups:control group, H2O2 group, Sal low dose group (30 µmol/L Sal+ H2O2 group), Sal middle dose group (50 µmol/L Sal+H2O2 group), Sal high dose group (100 µmol/L Sal+ H2O2 group). The effects of Sal on the apoptosis of the HLEC were determined by Hoechst 33258 staining and flow cytometry assay.Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect B cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cysteinyl aspartate specific proteinase 3 (Caspase-3) expression. Data between groups were analyzed using one-way analysis of variance (ANOVA), while LSD-t test was used for further comparison between every two groups. CCK-8 result showed that when the concentration of H2O2 was 200 µmol/L, the survival of HLEC inhibition rate was 49.56% ± 7.07%, which was close to the half of the cell survival inhibition rate (IC50). So 200 µmol/L was chosen as the concentration of H2O2 in follow-up experiments. Different concentrations of Sal had no inhibitive influence on HLEC viability. After 24 hours cultivated with Sal (10 µmol/L, 30 µmol/L, 50 µmol/L, 100 µmol/L, 200 µmol/L), the survival rate of HLEC were 100.24% ± 2.07%, 101.18% ± 2.14%, 101.32% ± 2.48%, 101.76% ± 1.93% and 99.28% ± 1.74% correspondingly. There was no significant difference comparing with that of the control group 99.84% ± 2.21% (F = 1.044, P = 0.415; all P > 0.05). Hoechst

  14. Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes

    NARCIS (Netherlands)

    Wilms, L.C.; Hollman, P.C.H.; Boots, A.W.; Kleinjans, J.C.S.

    2005-01-01

    Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of the flavonoid quercetin against the formation of oxidative DNA damage and bulky DNA adducts in human

  15. Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.

    OpenAIRE

    Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J

    1996-01-01

    Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal-suspension) Wa strain human rotavirus (which mimics human natural infection) developed diarrhea, and most pigs which recovered (87% protection rate) were immune to disease upon homologous virulent virus challenge at postinoculation day (PID) 21. Pigs inoculated with cell culture-attenuated Wa rotavirus (which mimics live oral vaccines) developed subclinical infections and seroconverted but were only partially protected agai...

  16. Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

    Science.gov (United States)

    Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

    2002-01-01

    Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

  17. Effect of adverse environmental conditions and protective clothing on temperature rise in a human body exposed to radiofrequency electromagnetic fields.

    Science.gov (United States)

    Moore, Stephen M; McIntosh, Robert L; Iskra, Steve; Lajevardipour, Alireza; Wood, Andrew W

    2017-07-01

    This study considers the computationally determined thermal profile of a finely discretized, heterogeneous human body model, simulating a radiofrequency electromagnetic field (RF-EMF) worker wearing protective clothing subject to RF-EMF exposure, and subject to various environmental conditions including high ambient temperature and high humidity, with full thermoregulatory mechanisms in place. How the human body responds in various scenarios was investigated, and the information was used to consider safety limits in current international RF-EMF safety guidelines and standards. It was found that different environmental conditions had minimal impact on the magnitude of the thermal response due to RF-EMF exposure, and that the current safety factor of 10 applied in international RF-EMF safety guidelines and standards for RF-EMF workers is generally conservative, though it is only narrowly so when workers are subjected to the most adverse environmental conditions. Bioelectromagnetics. 38:356-363, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Novel chimpanzee adenovirus-vectored respiratory mucosal tuberculosis vaccine: overcoming local anti-human adenovirus immunity for potent TB protection.

    Science.gov (United States)

    Jeyanathan, M; Thanthrige-Don, N; Afkhami, S; Lai, R; Damjanovic, D; Zganiacz, A; Feng, X; Yao, X-D; Rosenthal, K L; Medina, M Fe; Gauldie, J; Ertl, H C; Xing, Z

    2015-11-01

    Pulmonary tuberculosis (TB) remains to be a major global health problem despite many decades of parenteral use of Bacillus Calmette-Guérin (BCG) vaccine. Developing safe and effective respiratory mucosal TB vaccines represents a unique challenge. Over the past decade or so, the human serotype 5 adenovirus (AdHu5)-based TB vaccine has emerged as one of the most promising candidates based on a plethora of preclinical and early clinical studies. However, anti-AdHu5 immunity widely present in the lung of humans poses a serious gap and limitation to its real-world applications. In this study we have developed a novel chimpanzee adenovirus 68 (AdCh68)-vectored TB vaccine amenable to the respiratory route of vaccination. We have evaluated AdCh68-based TB vaccine for its safety, T-cell immunogenicity, and protective efficacy in relevant animal models of human pulmonary TB with or without parenteral BCG priming. We have also compared AdCh68-based TB vaccine with its AdHu5 counterpart in both naive animals and those with preexisting anti-AdHu5 immunity in the lung. We provide compelling evidence that AdCh68-based TB vaccine is not only safe when delivered to the respiratory tract but, importantly, is also superior to its AdHu5 counterpart in induction of T-cell responses and immune protection, and limiting lung immunopathology in the presence of preexisting anti-AdHu5 immunity in the lung. Our findings thus suggest AdCh68-based TB vaccine to be an ideal candidate for respiratory mucosal immunization, endorsing its further clinical development in humans.

  19. Use of "excess" human embryos for stem cell research: protecting women's rights and health.

    Science.gov (United States)

    Cohen, C B

    2000-01-01

    Proposed National Institutes of Health guidelines for stem cell research are too narrowly drawn and do not adequately protect the freedom of choice and health of women who donate embryos. They need to be expanded to cover not only the point of embryo donation, but also that of embryo creation. Guidelines are provided to ensure that donors undergoing hyperstimulation and egg retrieval gave voluntary informed consent to the production of embryos that might later prove in excess. A standard for determining when embryos have been overproduced is presented to address the possibility that additional embryos will be created for stem cell research in violation of the guidelines and at risk to women's health.

  20. Protection of neurons derived from human neural progenitor cells by veratridine.

    Science.gov (United States)

    Morgan, Peter J; Ortinau, Stefanie; Frahm, Jana; Krüger, Norman; Rolfs, Arndt; Frech, Moritz J

    2009-08-26

    The survival of developing dopaminergic neurons has been shown to be modulated by voltage-dependent mechanisms. Manipulation of these mechanisms in human neural progenitor cell cultures could improve the survival of immature dopaminergic neurons, and therefore aid research into pharmacological and cell replacement therapies for Parkinson's disease. Here, we examined the effect of the Na+ channel agonist veratridine on the human fetal neural progenitor ReNcell VM cell line. Neuronal differentiation was determined by immunocytochemistry, whereas patch clamp recordings showed the expression of functional voltage-gated sodium channels. Our results show that veratridine is neuroprotective in human fetal neural progenitor cells, which may benefit studies investigating neuronal development by reducing premature death amongst developing neurons.

  1. Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity

    Directory of Open Access Journals (Sweden)

    Yongjie Li

    2015-01-01

    Full Text Available Amyloid beta-peptides (Aβ are known to undergo active transport across the blood-brain barrier, and cerebral amyloid angiopathy has been shown to be a prominent feature in the majority of Alzheimer׳s disease. Quercetin is a natural flavonoid molecule and has been demonstrated to have potent neuroprotective effects, but its protective effect on endothelial cells under Aβ-damaged condition is unclear. In the present study, the protective effects of quercetin on brain microvascular endothelial cells injured by fibrillar Aβ1–40 (fAβ1–40 were observed. The results show that fAβ1–40-induced cytotoxicity in human brain microvascular endothelial cells (hBMECs can be relieved by quercetin treatment. Quercetin increases cell viability, reduces the release of lactate dehydrogenase, and relieves nuclear condensation. Quercetin also alleviates intracellular reactive oxygen species generation and increases superoxide dismutase activity. Moreover, it strengthens the barrier integrity through the preservation of the transendothelial electrical resistance value, the relief of aggravated permeability, and the increase of characteristic enzyme levels after being exposed to fAβ1–40. In conclusion, quercetin protects hBMECs from fAβ1–40-induced toxicity.

  2. Evaluation of protective efficacy of respiratory syncytial virus vaccine against A and B subgroup human isolates in Korea.

    Directory of Open Access Journals (Sweden)

    Ji-Eun Jang

    Full Text Available Human respiratory syncytial virus (HRSV is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. HRSV is divided into two subgroups, HRSV-A and HRSV-B, based on sequence variation within the G gene. Despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for HRSV. In this study, we have detected and identified the HRSV by RT-PCR from nasopharyngeal aspirates of Korean pediatric patients. Interestingly, all HRSV-B isolates exhibited unique deletion of 6 nucleotides and duplication of 60 nucleotides in the G gene. We successfully amplified two isolates ('KR/A/09-8' belonging to HRSV-A and 'KR/B/10-12' to HRSV-B on large-scale, and evaluated the cross-protective efficacy of our recombinant adenovirus-based HRSV vaccine candidate, rAd/3xG, by challenging the immunized mice with these isolates. The single intranasal immunization with rAd/3xG protected the mice completely from KR/A/09-8 infection and partially from KR/B/10-12 infection. Our study contributes to the understanding of the genetic characteristics and distribution of subgroups in the seasonal HRSV epidemics in Korea and, for the first time, to the evaluation of the cross-protective efficacy of RSV vaccine against HRSV-A and -B field-isolates.

  3. Lentivector-mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model.

    Science.gov (United States)

    Dowd, Eilís; Monville, Christelle; Torres, Eduardo M; Wong, Liang-Fong; Azzouz, Mimoun; Mazarakis, Nicholas D; Dunnett, Stephen B

    2005-11-01

    Although viral vector-mediated delivery of glial cell-line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose-pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre-treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV-GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV-GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug-induced rotational asymmetry. This study confirms that GDNF can protect against 6-OHDA-induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV-based vectors for the treatment of PD.

  4. REGIONAL GOVERNMENT'S RESPONSIBILITY TO THE PROTECTION OF INDONESIAN WORKER EMPLOYED (TKIs ABROAD (Review of Human Rights Perspective

    Directory of Open Access Journals (Sweden)

    Asri Lasatu

    2017-06-01

    Full Text Available The purpose of the establishment of the Republic of Indonesia is to protect and realize the welfare of citizens. Therefore, the main responsibility of the government is to provide protection and guarantee to every citizen to get a job and a decent living for humanity. Limitations of domestic employment, as well as the public's desire to work overseas, should be responded positively by the government, by formulating regulations both at the central and regional levels. This study will examine the roles and responsibilities of local governments as an effort the law protection against Indonesian Migrant Worker working abroad.This research is a normative legal research with approach of legislation and concept approach and analyzed qualitatively to give perspective on legal issue to the object of this research study. The results show that the responsibility of local government, especially in the pre-placement, post-placement, and empowerment phase of placement of migrant workers, while the placement of migrant workers is the responsibility of the central government. Implementation of local government responsibilities should be supported by regulations established by local governments.

  5. Quantifying behavioural interactions between humans and mosquitoes: Evaluating the protective efficacy of insecticidal nets against malaria transmission in rural Tanzania

    Directory of Open Access Journals (Sweden)

    Mathenge Evan

    2006-11-01

    Full Text Available Abstract Background African malaria vectors bite predominantly indoors at night so sleeping under an Insecticide-Treated Net (ITN can greatly reduce malaria risk. Behavioural adaptation by mosquitoes to increasing ITN coverage could allow vector mosquitoes to bite outside of peak sleeping hours and undermine efficacy of this key malaria prevention measure. Methods High coverage with largely untreated nets has been achieved in the Kilombero Valley, southern Tanzania through social marketing programmes. Direct surveys of nightly biting activity by An. gambiae Giles were conducted in the area before (1997 and after (2004 implementation of ITN promotion. A novel analytical model was applied to estimate the effective protection provided by an ITN, based on published experimental hut trials combined with questionnaire surveys of human sleeping behaviour and recorded mosquito biting patterns. Results An. gambiae was predominantly endophagic and nocturnal in both surveys: Approximately 90% and 80% of exposure occurred indoors and during peak sleeping hours, respectively. ITNs consistently conferred >70% protection against exposure to malaria transmission for users relative to non-users. Conclusion As ITN coverage increases, behavioural adaptation by mosquitoes remains a future possibility. The approach described allows comparison of mosquito biting patterns and ITN efficacy at multiple study sites and times. Initial results indicate ITNs remain highly effective and should remain a top-priority intervention. Combined with recently developed transmission models, this approach allows rapid, informative and cost-effective preliminary comparison of diverse control strategies in terms of protection against exposure before more costly and intensive clinical trials.

  6. Hydrogen-rich PBS protects cultured human cells from ionizing radiation-induced cellular damage

    Directory of Open Access Journals (Sweden)

    Qian Liren

    2010-01-01

    Full Text Available Hydroxyl radicals play an important role in ionizing radiation-induced cellular damage, while hydrogen can selectively reduce hydroxyl radicals in vitro. This study was designed to test the hypothesis that hydrogen-rich PBS may be an effective radioprotective agent in vitro. Compared to cells pretreated without hydrogen, we demonstrated that treating cells with hydrogen-rich PBS before irradiation could significantly inhibit IR-induced apoptosis, increase viability of human intestinal crypt cells, significantly increase endogenous antioxidant, and decrease malondialdehyde and 8-hydroxydeoxyguanosine concentrations of human lymphocyte AHH-1 cells. It is concluded that hydrogen has a potential as an effective and safe radioprotective agent.

  7. Protective Effect of Sundakai (Solanum torvum) Seed Protein (SP) Against Oxidative Membrane Damage in Human Erythrocytes.

    Science.gov (United States)

    Sivapriya, M; Gowda, S S Thammanna; Srinivas, Leela

    2015-12-01

    Lipid peroxidation by ROS at the membrane level disturbs the inherit integrity of components activating subsequent alterations in the function. In this study, the protective effect of purified Sundakai (Solanum torvum) seed protein (SP) was tested against oxidative membrane damage in erythrocyte membrane. SP prevented oxidative RBC lysis induced by pro-oxidants; Fe:As (2:20 μmol), periodate (0.4 mM), and t-BOOH (1 mM) up to 86, 81, and 86 %, respectively. Further, SP prevented the Fe:As-induced K(+) leakage up to the tune of 95 %. The inhibition offered by SP on K(+) leakage was comparable to inhibition offered by quinine sulfate, a known K(+) channel blocker. SP dose dependently restored Na(+)K(+) ATPase and Ca(2+)Mg(2+) ATPase activities in erythrocyte membrane. The restoration of ATPase activity by SP was two times more than standard antioxidants BHA and α-tocopherol. Besides, SP at 1.6 μmol restored the membrane proteins over Fe:As induction when analyzed by SDS-PAGE, which was comparable to protection offered by BHA. In conclusion, SP is an effective antioxidant in preventing oxidative membrane damage and associated functions mediated by ROS. As SP is non-toxic, it can be used as an effective bioprotective antioxidant agent to cellular components.

  8. Maytenus ilicifolia dry extract protects normal cells, induces apoptosis and regulates Bcl-2 in human cancer cells.

    Science.gov (United States)

    Araújo Júnior, Raimundo Fernandes de; Oliveira, Ana Luiza Cabral de Sá Leitão; Pessoa, Jonas Bispo; Garcia, Vinícios Barreto; Guerra, Gerlane Coelho Bernardo; Soares, Luiz Alberto Lira; Souza, Tatiane Pereira de; Petrovick, Pedro Ros; Araújo, Aurigena Antunes de

    2013-11-01

    Maytenus is the largest genus of the family Celastraceae and the species Maytenus ilicifolia (popularly known as 'Espinheira Santa'). It is widely used in traditional Brazilian medicine to treat stomach conditions including nausea, gastritis, and ulcers. In this study, the apoptotic effects of a spray-dried extract of M. ilicifolia (SDEMI) was evaluated using human hepatocellular cells (HepG2), colorectal carcinoma cells (HT-29), and normal keratinocytes (HaCaT). Cells were treated with SDEMI for 4 and 24 h, then were assayed for levels of apoptosis, caspase-3, and Bcl-2 by flow cytometry, immunostaining, and Western blot, respectively. Significant differences between groups were determined using analysis of variance (P < 0.05). For HepG2 and HT-29 cells treated with SDEMI, various cytotoxic effects were observed compared with control cells at all timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were observed, consistent with the induction of cell death detected in these cell lines. In contrast, treatment of HaCaT cells with SDEMI was associated with a protective effect compared with control cells at both timepoints (P < 0.001). For example, increased expression of Bcl-2 and negative caspase-3 staining were detected. Taken together, these results suggest that SDEMI protects normal cells, while SDEMI mediates induction of apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human carcinoma cells.

  9. A dry extract of Phyllanthus niruri protects normal cells and induces apoptosis in human liver carcinoma cells.

    Science.gov (United States)

    de Araújo Júnior, Raimundo Fernandes; de Souza, Tatiane Pereira; Pires, Júlia Glória Lucatelli; Soares, Luiz Alberto Lira; de Araújo, Aurigena Antunes; Petrovick, Pedro Ros; Mâcedo, Helainy Daline Oliveira; de Sá Leitão Oliveira, Ana Luiza Cabral; Guerra, Gerlane Coelho Bernardo

    2012-11-01

    The ability to induce apoptosis is an important marker for cytotoxic antitumor agents. Some natural compounds have been shown to modulate apoptosis pathways that are frequently blocked in human cancers, and therefore, these compounds provide novel opportunities for cancer drug development. Phyllanthus, a plant genus of the family Euphorbiaceae, exhibits multiple pharmacological actions. Of these, Phyllanthus niruri extracts exhibit significant antitumor activity, which is consistent with the traditional medicinal use of this plant. To examine the apoptotic effects of a spray-dried extract of P. niruri (SDEPN), human hepatocellular carcinoma cells (HepG2, Huh-7), colorectal carcinoma cells (Ht29) and keratinocytes (HaCaT) were exposed to the extract for 4, 8 and 24 h. Flow cytometry and caspase-3 immunostaining were used to detect apoptosis, while analysis of variance was applied to identify significant differences between groups (P < 0.05). At all timepoints, the SDEPN induced significantly different cytotoxic effects for HepG2 and Huh-7 cells compared with control cells (P < 0.001). In contrast, the SDEPN had a protective effect on HaCaT cells compared with control cells at all timepoints (P < 0.001). In caspase-3 assays, activation was detected after cell death was induced in Huh-7 and HepG2 cancer cells by the SDEPN. In combination, these results indicate that the SDEPN is selectively toxic towards cancer cell lines, yet is protective towards normal cells.

  10. Life Support and Habitation Systems: Crew Support and Protection for Human Exploration Missions Beyond Low Earth Orbit

    Science.gov (United States)

    Barta, Daniel J.; McQuillan, Jeffrey

    2011-01-01

    The National Aeronautics and Space Administration (NASA) has recently expanded its mission set for possible future human exploration missions. With multiple options there is interest in identifying technology needs across these missions to focus technology investments. In addition to the Moon and other destinations in cis-lunar space, other destinations including Near Earth Objects and Mars have been added for consideration. Recently, technology programs and projects have been re-organizing to better meet the Agency s strategic goals and address needs across these potential future missions. Life Support and Habitation Systems (LSHS) is one of 10 Foundational Domains as part of the National Aeronautics and Space Administration s Exploration Technology Development Program. The chief goal of LSHS is to develop and mature advanced technologies to sustain human life on missions beyond Low Earth Orbit (LEO) to increase reliability, reduce dependency on resupply and increase vehicle self-sufficiency. For long duration exploration missions, further closure of life support systems is of interest. Focus includes key technologies for atmosphere revitalization, water recovery, waste management, thermal control and crew accommodations. Other areas of focus include technologies for radiation protection, environmental monitoring and fire protection. The aim is to recover additional consumable mass, reduce requirements for power, volume, heat rejection, crew involvement, and meet exploration vehicle requirements. This paper provides a brief description of the LSHS Foundational Domain as defined for fiscal year 2011.

  11. Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

    Directory of Open Access Journals (Sweden)

    Victor Paromov

    2011-01-01

    Full Text Available Sulfur mustard or mustard gas (HD and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES, or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes increased cell viability and attenuated production of reactive oxygen species (ROS in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

  12. Dimethoate-induced oxidative stress in human erythrocytes and the protective effect of vitamins C and E in vitro.

    Science.gov (United States)

    Abdallah, Fatma Ben; Gargouri, Bochra; Bejaoui, Hafedh; Lassoued, Saloua; Ammar-Keskes, Leila

    2011-06-01

    Organophosphorus insecticides may induce oxidative stress leading to the generation of free radicals and alteration in the antioxidant system. The aim of this study was to examine the potency of Dimethoate (Dim) to induce oxidative stress response in human erythrocyte in vitro and the role of Vitamins C (Vit C) and E (Vit E) in alleviating the cytotoxic effects. Erythrocytes were divided into three groups. The first group, erythrocytes were incubated for 4 h at 37 °C with different concentrations (0, 20, 40, 60, 80, and 100 mM) of Dim. The second and third groups were preincubated with Vit C or Vit E, respectively, for 30 min and followed by Dim incubation for 4 h at 37 °C. Following in vitro exposure, Dim caused a significant increase in malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) in erythrocytes at different concentrations. Vit E or Vit C pretreated erythrocytes showed a significant protection against the cytotoxic effects inducted by Dim on the studied parameters. In conclusion, antioxidant Vit E and C could protect against Dim-induced oxidative stress by decreasing lipid peroxidation and hyperactivity of SOD and CAT in human erythrocytes. Copyright © 2010 Wiley Periodicals, Inc.

  13. Extract from Armoracia rusticana and its flavonoid components protect human lymphocytes against oxidative damage induced by hydrogen peroxide.

    Science.gov (United States)

    Gafrikova, Michala; Galova, Eliska; Sevcovicova, Andrea; Imreova, Petronela; Mucaji, Pavel; Miadokova, Eva

    2014-03-14

    DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H₂O₂ genotoxicity using the A. rusticana root aqueous extract (AE) and two flavonoids (kaempferol or quercetin). Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H₂O₂ and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H₂O₂ we proved that the 0.0025 mg·mL⁻¹ concentration of AE protected human DNA. It significantly reduced H₂O₂-induced oxidative damage (from 78% to 35.75%). Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL⁻¹) significantly diminished oxidative DNA damage (from 83.3% to 19.4%), and the same concentration of quercetin also reduced the genotoxic effect of H₂O₂ (from 83.3% to 16.2%). We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties.

  14. Epigallocatechin-3-Gallate Protects Erythrocyte Ca2+-ATPase and Na+/K+-ATPase Against Oxidative Induced Damage During Aging in Humans

    Directory of Open Access Journals (Sweden)

    Prabhanshu Kumar

    2014-10-01

    Full Text Available Purpose: The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Methods: Human erythrocyte membrane bound Ca2+-ATPase and Na+/K+-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10-7M to 10-4M to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10-5 M final concentration. Results: We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca2+-ATPase and Na+/K+-ATPase during aging in humans. We have detected a significant (p < 0.001 decreased activity of Ca2+-ATPase and Na+/K+ -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Conclusion: Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca2+-ATPase and Na+/K+ -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

  15. Genetically Engineered Human Islets Protected From CD8-mediated Autoimmune Destruction In Vivo

    NARCIS (Netherlands)

    Zaldumbide, Arnaud; Alkemade, Gonnie; Carlotti, Francoise; Nikolic, Tatjana; Abreu, Joana R. F.; Engelse, Marten A.; Skowera, Anja; de Koning, Eelco J.; Peakman, Mark; Roep, Bart O.; Hoeben, Rob C.; Wiertz, Emmanuel J. H. J.

    Islet transplantation is a promising therapy for type 1 diabetes, but graft function and survival are compromised by recurrent islet autoimmunity. Immunoprotection of islets will be required to improve clinical outcome. We engineered human beta cells to express herpesvirus-encoded immune-evasion

  16. Analyzing the EU Refugee Crisis : Humanity, Heritage and Responsibility to Protect

    NARCIS (Netherlands)

    Hadfield, Amelia; Zwitter, Andrej

    2015-01-01

    2015 has shaken the EU to its core. Hard upon the heels of geopolitical upheavals in Ukraine, as well as internal battles to define both Eurozone and energy governance, the refugee crisis has prompted a sober reckoning of the EU’s competence and its humanity. With an increasing number of articles

  17. Human transformation of ecosystems: Comparing protected andunprotected areas with natural baselines

    Czech Academy of Sciences Publication Activity Database

    Vačkář, David; Harmáčková, Veronika Zuzana; Kaňková, H.; Stupková, K.

    2016-01-01

    Roč. 66, JUL (2016), s. 321-328 ISSN 1470-160X R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : Human appropriation of net primaryproduction (HANPP) * Mean species abundance (MSA) * Net carbon storage * Biophysical indicatorsa Subject RIV: EH - Ecology, Behaviour Impact factor: 3.898, year: 2016

  18. Patterns of Human Development Indicators across Constitutional Analysis of Children's Rights to Protection, Provision, and Participation

    Science.gov (United States)

    Habashi, Janette; Wright, Lynne; Hathcoat, John D.

    2012-01-01

    This study examines children's images in constitutions and/or amendments as articulated in the Convention on the Rights of the Child while they intersect with the three dimensions of the Human Development Index (HDI) of 2008: life expectancy, educational index, and GDP. The connection between the images of the child and the fulfillment of the…

  19. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning.

    Science.gov (United States)

    Huang, Yue-Jin; Huang, Yue; Baldassarre, Hernan; Wang, Bin; Lazaris, Anthoula; Leduc, Martin; Bilodeau, Annie S; Bellemare, Annie; Côté, Mélanie; Herskovits, Peter; Touati, Madjid; Turcotte, Carl; Valeanu, Loredana; Lemée, Nicolas; Wilgus, Harvey; Bégin, Isabelle; Bhatia, Bhim; Rao, Khalid; Neveu, Nathalie; Brochu, Eric; Pierson, Janice; Hockley, Duncan K; Cerasoli, Douglas M; Lenz, David E; Karatzas, Costas N; Langermann, Solomon

    2007-08-21

    Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat beta-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.

  20. To survive and protect: testosterone and the neuroendocrinology of human social behavior

    NARCIS (Netherlands)

    Bos, P.A.|info:eu-repo/dai/nl/337018995

    2012-01-01

    The studies reported in this thesis show that despite the development that the human brain has undergone during evolution, this organ and the behavior it brings forth is still strongly sensitive to the effects of testosterone. Testosterone strengthens the neural response to sounds of crying babies,

  1. 76 FR 5735 - Revisions to EPA's Rule on Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2011-02-02

    ... in its 2004 Report to EPA, and from the Nuremberg Code. The amendments proposed here would make no... the principles of the Nuremberg Code with respect to human experimentation; and shall establish an..., as suggested by Recommendation 5-5 from the 2004 NAS Report. 3. Inconsistency with the Nuremberg Code...

  2. Human impact on wildlife populations within a protected Central African forest

    NARCIS (Netherlands)

    Blom, A.; Heitkönig, I.M.A.; Prins, H.H.T.; Zalinge, van R.; Mbea, E.

    2004-01-01

    This paper addresses the effect of human activities on the density of large mammals in the Dzanga-Ndoki National Park and the adjacent Dzanga-Sangha Reserve in the Central African Republic. Between six and eight 20 km long permanent transects were walked on a monthly basis from January 1997 to

  3. Antioxidant activity of herbaceous plant extracts protect against hydrogen peroxide-induced DNA damage in human lymphocytes

    Science.gov (United States)

    2013-01-01

    Background Herbaceous plants containing antioxidants can protect against DNA damage. The purpose of this study was to evaluate the antioxidant substances, antioxidant activity, and protection of DNA from oxidative damage in human lymphocytes induced by hydrogen peroxide (H2O2). Our methods used acidic methanol and water extractions from six herbaceous plants, including Bidens alba (BA), Lycium chinense (LC), Mentha arvensis (MA), Plantago asiatica (PA), Houttuynia cordata (HC), and Centella asiatica (CA). Methods Antioxidant compounds such as flavonol and polyphenol were analyzed. Antioxidant activity was determined by the inhibition percentage of conjugated diene formation in a linoleic acid emulsion system and by trolox-equivalent antioxidant capacity (TEAC) assay. Their antioxidative capacities for protecting human lymphocyte DNA from H2O2-induced strand breaks was evaluated by comet assay. Results The studied plants were found to be rich in flavonols, especially myricetin in BA, morin in MA, quercetin in HC, and kaemperol in CA. In addition, polyphenol abounded in BA and CA. The best conjugated diene formation inhibition percentage was found in the acidic methanolic extract of PA. Regarding TEAC, the best antioxidant activity was generated from the acidic methanolic extract of HC. Water and acidic methanolic extracts of MA and HC both had better inhibition percentages of tail DNA% and tail moment as compared to the rest of the tested extracts, and significantly suppressed oxidative damage to lymphocyte DNA. Conclusion Quercetin and morin are important for preventing peroxidation and oxidative damage to DNA, and the leaves of MA and HC extracts may have excellent potential as functional ingredients representing potential sources of natural antioxidants. PMID:24279749

  4. Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans.

    Directory of Open Access Journals (Sweden)

    Leonie K Heilbronn

    Full Text Available Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21, fatty acid binding protein-4 (FABP4, lipocalin-2 and plasminogen activator factor-1 (PAI1 were assessed. Statistics were performed by repeated measures ANOVA.Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05. Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001 and adiponectin was also elevated at day 28 (P=0.001. FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state.www.clinicaltrials.gov (NCT00562393.

  5. Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre.

    Science.gov (United States)

    Gould, Victoria M W; Francis, James N; Anderson, Katie J; Georges, Bertrand; Cope, Alethea V; Tregoning, John S

    2017-01-01

    In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines.

  6. Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line.

    Science.gov (United States)

    Almeida, I F; Pinto, A S; Monteiro, C; Monteiro, H; Belo, L; Fernandes, J; Bento, A R; Duarte, T L; Garrido, J; Bahia, M F; Sousa Lobo, J M; Costa, P C

    2015-03-01

    Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 μg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on (1)O₂ mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 μg/mL. This effect was found to be related to a direct antioxidant effect (involving (1)O₂) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 μg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.

    Directory of Open Access Journals (Sweden)

    Wenlu Li

    Full Text Available Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC, protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT formation, cell account, lactate dehydrogenase (LDH release and Rhodamine 123 staining. Advanced glycation end-products (AGEs formation and receptor for advanced glycation end-products (RAGE expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

  8. The Roma Community and International Institutions: Only Relative Success in the Protection of Human and Minority Rights

    Directory of Open Access Journals (Sweden)

    Jagoda Novak

    2004-12-01

    Full Text Available The paper treats problems pertaining to the legislative framework, as well as to the practical implementation of mechanisms for the protection of the human and minority rights of the Roma community. Special emphasis is placed on international and European protective mechanisms, on the pressure that they exert on national states, as well as on their frameworks for protecting the human rights of the Roma community, which – in view of the absence of a mother state in this case – is the only guarantee for the respect of Roma human rights. International frameworks and activities are also the only guarantee assuring the social integration of the Roma, a goal towards which modern European society strives. The paper attempts to determine the position of Croatia in respect to European countries in this matter, with special reference to problems in education faced by the Roma community and on the experience of the non-governmental and donator sector in regard to work with the Roma community. An overview of existing documents and acts reveals that a legislative framework for respecting Roma rights already exists, and that the European Union just has to supplement it with a legislative document exclusively dealing with the problems of the Roma, given the specific aspects of realising the human rights of members of this community. In the implementation of legislative acts, however, there is a series of inconsistencies, resulting from inadequate monitoring of the implementation of European documents, from an absence of repercussions for non-implementing them and from an imbalanced approach to old and new members of the European Union. In the context of association with the European community of states, Croatia has an opportunity to improve the position of its Roma community in a relatively short period of time and to accelerate the social integration of the Roma, although – due to an unsatisfactory and non-systematic approach, no consultations with

  9. UVB-Protective Effects of Isoflavone Extracts from Soybean Cake in Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Chi-Feng Hung

    2007-07-01

    Full Text Available It has been shown by chromatography that aglycone, glucoside, acetylglucosideand malonylglucoside isoflavone extracts prepared from soybean cake showed betterantioxidant activities than isoflavone standards. Consequently, the aim of this study was toevaluate the protective effects of these isoflavone extracts against ultraviolet B (UVB-induced keratinocyte damage. Our results demonstrated that these soybean cake isoflavoneextracts could inhibit UVB-induced keratinocyte death. Moreover, they could inhibit UVB-induced intracellular release of hydrogen peroxide (H2O2 Furthermore, these isoflavoneextracts differentially inhibited UVB-induced MAPK phosphorylation. The ERK1/2 andp38 phosphorylation was not inhibited by all tested isoflavone extracts, whereas JNKphosphorylation was inhibited by group I to group III isoflavone extracts. Since theseisoflavone extracts are relative stable and easily obtained than the isoflavone standards, wesuggest that soybean cake may be a useful potential source for developing effective skincare agents in against photoaging.

  10. MAX06 and FAX06: update of two adult human phantoms for radiation protection dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R [Departamento de Energia Nuclear, Universidade Federal de Pernambuco, Av. Prof. Luiz Freire 1000, Cidade Universitaria, CEP: 50740-540, Recife, PE (Brazil); Khoury, H J [Departamento de Energia Nuclear, Universidade Federal de Pernambuco, Av. Prof. Luiz Freire 1000, Cidade Universitaria, CEP: 50740-540, Recife, PE (Brazil); Vieira, J W [Centro Federal de Educacao Tecnologica de Pernambuco, Recife, PE (Brazil); Lima, V J M [Departamento de Anatomia, Universidade Federal de Pernambuco, Recife, PE (Brazil)

    2006-07-21

    The International Commission on Radiological Protection (ICRP) is currently preparing new recommendations which will replace those released in ICRP 1991, 1990 Recommendations of the ICRP ICRP Publication 60 (Oxford: Pergamon). The draft report previews a change for the effective dose with respect to the number of organs and tissues to be included in its calculation. In the future, adipose tissue, connective tissue, the extrathoracic airways, the gall bladder, the heart wall, the lymphatic nodes, the prostate and the salivary glands have to be taken into account for the determination of the effective dose. This study reports on a second segmentation of the recently introduced male adult voxel (MAX) and female adult voxel (FAX) phantoms with regard to the new organs and tissues, but also presents a revised representation of the skeletons, which had not been adjusted to ICRP-based volumes in the first release of the two phantoms.

  11. MAX06 and FAX06: update of two adult human phantoms for radiation protection dosimetry

    Science.gov (United States)

    Kramer, R.; Khoury, H. J.; Vieira, J. W.; Lima, V. J. M.

    2006-07-01

    The International Commission on Radiological Protection (ICRP) is currently preparing new recommendations which will replace those released in ICRP 1991, 1990 Recommendations of the ICRP ICRP Publication 60 (Oxford: Pergamon). The draft report previews a change for the effective dose with respect to the number of organs and tissues to be included in its calculation. In the future, adipose tissue, connective tissue, the extrathoracic airways, the gall bladder, the heart wall, the lymphatic nodes, the prostate and the salivary glands have to be taken into account for the determination of the effective dose. This study reports on a second segmentation of the recently introduced male adult voxel (MAX) and female adult voxel (FAX) phantoms with regard to the new organs and tissues, but also presents a revised representation of the skeletons, which had not been adjusted to ICRP-based volumes in the first release of the two phantoms.

  12. VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

    Science.gov (United States)

    Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

    2011-01-01

    Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major

  13. An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement.

    Science.gov (United States)

    Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J; Oei, Anneke; Nijhof, Ard M; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D; Hovius, Joppe W R

    2016-04-01

    We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI. We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro. We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing. We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.

  14. Protective effects of Spirulina on the liver function and hyperlipidemia of rats and human

    Directory of Open Access Journals (Sweden)

    Mostafa Mohamed El-Sheekh

    2014-02-01

    Full Text Available In the present study, the effects of Spirulina on subchronic treatments (two weeks of hyperlipidemia and liver function of the rats and humans were investigated. The hyperlipidemia was induced in the rats using 25% of soya bean oil and 25% butter. The butter induced more hyperlipidemia than soya bean oil. Spirulina was used at the concentrations of 0, 2.5, 5.0 and 10 % of diet weight of the rats. The decrease in hyperlipidemia by Spirulina was dependent on its concentration in the diet. In case of human studies, about four g/day of Spirulina was taken via oral administration by Egyptian volunteers patients with hyperlipidemia. Spirulina decreased the levels of hyperlipidemia in these patients. The effects were dependent on the amount and number of administered dose of Sprirulina. The results suggested that the Spirulina treatment could induce marked reduction of aminotransferase through correcting lipid profile and increasing high density lipoprotein.

  15. Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

    Directory of Open Access Journals (Sweden)

    S. Carrión

    2016-12-01

    Full Text Available This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes.

  16. Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever.

    Science.gov (United States)

    Mire, Chad E; Cross, Robert W; Geisbert, Joan B; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Heinrich, Megan L; Rowland, Megan M; Goba, Augustine; Momoh, Mambu; Boisen, Mathew L; Grant, Donald S; Fullah, Mohamed; Khan, Sheik Humarr; Fenton, Karla A; Robinson, James E; Branco, Luis M; Garry, Robert F; Geisbert, Thomas W

    2017-10-01

    There are no approved treatments for Lassa fever, which is endemic to the same regions of West Africa that were recently devastated by Ebola. Here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of Lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.

  17. Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function

    OpenAIRE

    Ghaffari Mohammad Ali; Hoseinzadeh Pooneh; Hashemitabar Mahmoud; Zeinali Majid

    2016-01-01

    Background Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoid...

  18. Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function

    OpenAIRE

    Jamalan, Mostafa; Ghaffari, Mohammad Ali; Hoseinzadeh, Pooneh; Hashemitabar, Mahmoud; Zeinali, Majid

    2016-01-01

    Background Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (...

  19. Single-dose protection against Plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron A.

    Science.gov (United States)

    Sridhar, S; Reyes-Sandoval, A; Draper, S J; Moore, A C; Gilbert, S C; Gao, G P; Wilson, J M; Hill, A V S

    2008-04-01

    Human adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigen Plasmodium berghei circumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8(+) T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.

  20. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans.

    Science.gov (United States)

    Sivapirabu, G; Yiasemides, E; Halliday, G M; Park, J; Damian, D L

    2009-12-01

    Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown. To determine the effects and mechanisms of topical nicotinamide on UV-induced suppression of delayed type hypersensitivity (DTH) responses in humans. Healthy Mantoux-positive volunteers in four randomised, double-blinded studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0.2% or 5%) or its vehicle were applied immediately after each irradiation. Mantoux testing was performed at irradiated sites and adjacent unirradiated control sites 48 h after the first irradiation and measured 72 h later. Immunosuppression was calculated as the difference in Mantoux-induced erythema and induration at test sites compared to control sites. Human keratinocyte cell cultures, with and without ssUV and nicotinamide, were used for quantitative real-time reverse transcriptase-polymerase chain reaction assessment of TP53 and enzymes that regulate oxidative phosphorylation. Nicotinamide cooperated with ssUV to increase enzymes involved in cellular energy metabolism and p53, and significantly protected against immunosuppression caused by UVB, longwave UVA and single and repeated ssUV exposures. Longwave UVA, which is poorly filtered by most sunscreens, was highly immune suppressive even at doses equivalent to 20 min of sun exposure. Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.

  1. High protective efficacy of probiotics and rice bran against human norovirus infection and diarrhea in gnotobiotic pigs

    Directory of Open Access Journals (Sweden)

    Shaohua Lei

    2016-11-01

    Full Text Available Probiotics have been recognized as vaccine adjuvants and therapeutic agents to treat acute gastroenteritis in children. We previously showed that rice bran reduced human rotavirus diarrhea in gnotobiotic pigs. Human noroviruses (HuNoVs are the major pathogens causing nonbacterial acute gastroenteritis worldwide. In this study, Lactobacillus rhamnosus GG (LGG and Escherichia coli Nissle 1917 (EcN were first screened for their ability to bind HuNoV P particles and virions derived from clinical samples containing HuNoV genotype GII.3 and GII.4, then the effects of LGG+EcN and rice bran on HuNoV infection and diarrhea were investigated using the gnotobiotic pig model. While LGG+EcN colonization inhibited HuNoV shedding, probiotic cocktail regimens in which rice bran feeding started 7 days prior to or 1 day after viral inoculation in the LGG+EcN colonized gnotobiotic pigs exhibited high protection against HuNoV diarrhea and shedding, characterized by significantly reduced incidence (89% versus 20% and shorter mean duration of diarrhea (2.2 versus 0.2 days, as well as shorter mean duration of virus shedding (3.2 versus 1.0 days. In both probiotic cocktail groups, the diarrhea reduction rates were 78% compared with the control group, and diarrhea severity was reduced as demonstrated by the significantly lower cumulative fecal scores. The high protective efficacy of the probiotic cocktail regimens was attributed to stimulation of IFN-γ+ T cell responses, increased production of intestinal IgA and IgG, and maintenance of healthy intestinal morphology (manifested as longer villi compared with the control group. Therefore, probiotic cocktail regimens containing LGG+EcN and rice bran may represent highly efficacious strategies to prevent and treat HuNoV gastroenteritis, and potentially other human enteric pathogens.

  2. Adrenergic Stress Protection of Human iPS Cell-Derived Cardiomyocytes by Fast Kv7.1 Recycling

    Directory of Open Access Journals (Sweden)

    Ilaria Piccini

    2017-09-01

    Full Text Available The fight-or-flight response (FFR, a physiological acute stress reaction, involves positive chronotropic and inotropic effects on heart muscle cells mediated through β-adrenoceptor activation. Increased systolic calcium is required to enable stronger heart contractions whereas elevated potassium currents are to limit the duration of the action potentials and prevent arrhythmia. The latter effect is accomplished by an increased functional activity of the Kv7.1 channel encoded by KCNQ1. Current knowledge, however, does not sufficiently explain the full extent of rapid Kv7.1 activation and may hence be incomplete. Using inducible genetic KCNQ1 complementation in KCNQ1-deficient human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs, we here reinvestigate the functional role of Kv7.1 in adapting human CMs to adrenergic stress. Under baseline conditions, Kv7.1 was barely detectable at the plasma membrane of hiPSC-CMs, yet it fully protected these from adrenergic stress-induced beat-to-beat variability of repolarization and torsade des pointes-like arrhythmia. Furthermore, isoprenaline treatment increased field potential durations specifically in KCNQ1-deficient CMs to cause these adverse macroscopic effects. Mechanistically, we find that the protective action by Kv7.1 resides in a rapid translocation of channel proteins from intracellular stores to the plasma membrane, induced by adrenergic signaling. Gene silencing experiments targeting RAB GTPases, mediators of intracellular vesicle trafficking, showed that fast Kv7.1 recycling under acute stress conditions is RAB4A-dependent.Our data reveal a key mechanism underlying the rapid adaptation of human cardiomyocytes to adrenergic stress. These findings moreover aid to the understanding of disease pathology in long QT syndrome and bear important implications for safety pharmacological screening.

  3. Phenolic Compounds of Potato Peel Extracts: Their Antioxidant Activity and Protection against Human Enteric Viruses.

    Science.gov (United States)

    Silva-BeltrÁn, Norma Patricia; Chaidez-Quiroz, Cristóbal; López-Cuevas, Osvaldo; Ruiz-Cruz, Saul; López-Mata, Marco A; Del-Toro-SÁnchez, Carmen Lizette; Marquez-Rios, Enrique; Ornelas-Paz, José de Jesús

    2017-02-28

    Potato peels (PP) contain several bioactive compounds. These compounds are known to provide human health benefits, including antioxidant and antimicrobial properties. In addition, these compounds could have effects on human enteric viruses that have not yet been reported. The objective of the present study was to evaluate the phenolic composition, antioxidant properties in the acidified ethanol extract (AEE) and water extract of PP, and the antiviral effects on the inhibition of Av-05 and MS2 bacteriophages, which were used as human enteric viral surrogates. The AEE showed the highest phenolic content and antioxidant activity. Chlorogenic and caffeic acids were the major phenolic acids. In vitro analysis indicated that PP had a strong antioxidant activity. A 3 h incubation with AEE at a concentration of 5 mg/ml was needed to reduce the PFU/ml (plaque-forming unit per unit volume) of Av-05 and MS2 by 2.8 and 3.9 log₁₀, respectively, in a dose-dependent manner. Our data suggest that PP has potential to be a source of natural antioxidants against enteric viruses.

  4. Mathematical analysis of clinical data reveals a homunculus of bacterial mimotopes protecting from autoimmunity via oral tolerance in human.

    Science.gov (United States)

    Kristóf, Katalin; Madách, Krisztina; Czaller, Ibolya; Bajtay, Zsuzsa; Erdei, Anna

    2009-05-01

    Oral tolerance (OT) means systemic immunological unresponsiveness to harmless antigens present in the gastrointestinal tract. We presumed that tolerance to these antigens may also protect self-proteins that show immunological similarity to the intestinal normal flora. To investigate the existence and in vivo relevance of such a tolerogenic molecular mimicry, we focused our attention to Autoimmune Polyendocrine Syndrome type 1 (APS1) and Hemolysis, Elevated Liver Enzymes, Low Platelet count (HELLP) syndrome. APS1 is a human form of Autoimmune Regulator (AIRE) dysfunction with severely impaired central immunotolerance to a specific set of autoantigens, allowing investigation of tolerogenic mimicry by itself, without a disturbing background. HELLP syndrome is a mediocre manifestation of thrombotic microangiopathy, complicating pregnancy, with platelet-fibrin deposits in small blood vessels and transient development of autoantibodies. Impaired microcirculation in the liver is well described, while intestinal ischemia is possible but has not yet been studied. As the harmless nature of an antigen is essential for OT, ischemia-induced bacterial microinvasion represses this process. In case that oral tolerance to a bacterial homunculus is an existing way of self-protection and has an in vivo relevance when central tolerance is intact, significant intestinal ischemia--if present--is expected to promote autoimmunity in HELLP syndrome. We used an experimentally validated, highly reliable mathematical algorithm to predict the extent of immunological similarity between a certain autoantigen and intestinal bacteria. We found a strong negative correlation between the similarity of autoantigens to intestinal bacteria and the production of specific autoantibodies in APS1 (R=-0.70, P=0.002), while a positive correlation was observed in patients with predominantly the severe/moderately severe form of HELLP syndrome according to Mississippi classification (R=0.94, P=0

  5. IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model.

    Directory of Open Access Journals (Sweden)

    Celina G Vega

    Full Text Available Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV. Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization -VN- titer = 256 for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV-specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV. Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.

  6. Porcine complement regulators protect aortic smooth muscle cells poorly against human complement-induced lysis and proliferation: consequences for xenotransplantation.

    Science.gov (United States)

    Capey, Steven; van den Berg, Carmen W

    2005-05-01

    Accelerated atherosclerosis after transplantation has been observed and is characterized by smooth muscle cell proliferation in the graft. Porcine cells are frequently used in models of atherosclerosis and porcine organs are considered for use in transplantation. Complement (C) activation is known to play a major role in rejection of xenografts and is also considered to play a role in the development of atherosclerosis. The aim of this study was to investigate the expression and function of membrane bound regulators of complement (CReg) on porcine aortic smooth muscle cells (PASMC). The PASMC were assessed for expression of CReg and susceptibility to lysis by human C by flow-cytometry. The effect of various cytokines on CReg expression and C-susceptibility was investigated. The ability of human C to induce cell proliferation was assessed using the Alamar blue assay. The PASMC only express the CReg membrane cofactor protein (MCP) and CD59 on their cell surface. MCP expression was increased by interleukin (IL)-4. In contrast to porcine aortic endothelial cells (PAEC), PASMC were found to be surprisingly sensitive to C-mediated lysis, mainly due to a low level of expression of CD59. Human C-induced proliferation of PASMC, which was dependent on complete membrane attack complex (MAC) formation. Endogenously expressed CReg on PASMC poorly protect these cells to human C. Human C can induce proliferation of PASMC. In order to prevent accelerated atherosclerosis in porcine xenografts, increased levels of CReg not only have to be obtained on the endothelial cells but also on the smooth muscle cells.

  7. Analyzing the EU Refugee Crisis: Humanity, Heritage and Responsibility to Protect

    Directory of Open Access Journals (Sweden)

    Amelia Hadfield

    2015-11-01

    Full Text Available 2015 has shaken the EU to its core. Hard upon the heels of geopolitical upheavals in Ukraine, as well as internal battles to define both Eurozone and energy governance, the refugee crisis has prompted a sober reckoning of the EU’s competence and its humanity. With an increasing number of articles and Special Issues in Politics and Governance focusing upon key aspects of the EU as both a political actor, and a source of governance, our autumn 2015 editorial looks briefly at the significance of the refugee crisis in the context of the EU’s current response and future options.

  8. Defined plant extracts can protect human cells against combined xenobiotic effects

    Directory of Open Access Journals (Sweden)

    Clair Emilie

    2011-01-01

    Full Text Available Abstract Background Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts called Circ1, Dig1, Dig2, Sp1, and Uro1 in order to understand whether specific molecular actions took place or not. Methods Kidney and liver are major detoxification organs. We have studied embryonic kidney and hepatic human cell lines E293 and HepG2. The intoxication was induced on the one hand by a formulation of one of the most common herbicides worldwide, Roundup 450 GT+ (glyphosate and specific adjuvants, and on the other hand by a mixture of Bisphenol-A and Atrazine, all found in surface waters, feed and food. The prevention and curative effects of plant extracts were also measured on mitochondrial succinate dehydrogenase activity, on the entry of radiolabelled glyphosate (in Roundup in cells, and on cytochromes P450 1A2 and 3A4 as well as glutathione-S-transferase. Results Clear toxicities of pollutants were observed on both cell lines at very low sub-agricultural dilutions. The prevention of such phenomena took place within 48 h with the plant extracts tested, with success rates ranging between 25-34% for the E293 intoxicated by Roundup, and surprisingly up to 71% for the HepG2. By contrast, after intoxication, no plant extract was capable of restoring E293 viability within 48 h, however, two medicinal plant combinations did restore the Bisphenol-A/Atrazine intoxicated HepG2 up to 24-28%. The analysis of underlying mechanisms revealed that plant extracts were not capable of preventing radiolabelled glyphosate from entering cells; however Dig2 did restore the CYP1A2 activity disrupted by Roundup, and had only a mild preventive effect

  9. Management of risk to human health posed by dioxins under the Canadian Environmental Protection Act (CEPA)

    Energy Technology Data Exchange (ETDEWEB)

    Seed, L. [Health Canada, Ottawa, ON (Canada)

    2004-09-15

    The Canadian federal Toxic Substances Management Policy requires that for substances which: - are toxic - persist in the environment - bioaccumulate - result predominantly from human activity the ultimate goal is virtual elimination. Because dioxins and furans satisfy these criteria, the management objective is virtual elimination of measurable releases of these substances into the environment. Measurable releases are defined as releases above the Level of Quantification (LoQ), which is the lowest concentration that can be accurately measured using sensitive but routine sampling and analytical methods. For dioxins and furans released to air, that level is 32 picograms of toxic equivalents (TEQ) per cubic metre.

  10. An Alternatively Spliced Bifunctional Localization Signal Reprograms Human Shugoshin 1 to Protect Centrosomal Instead of Centromeric Cohesin

    Directory of Open Access Journals (Sweden)

    Lisa Mohr

    2015-09-01

    Full Text Available Separation of human sister chromatids involves the removal of DNA embracing cohesin ring complexes. Ring opening occurs by prophase-pathway-dependent phosphorylation and separase-mediated cleavage, with the former being antagonized at centromeres by Sgo1-dependent PP2A recruitment. Intriguingly, prophase pathway signaling and separase’s proteolytic activity also bring about centriole disengagement, whereas Sgo1 is again counteracting this licensing step of later centrosome duplication. Here, we demonstrate that alternative splice variants of human Sgo1 specifically and exclusively localize and function either at centromeres or centrosomes. A small C-terminal peptide encoded by exon 9 of SGO1 (CTS for centrosomal targeting signal of human Sgo1 is necessary and sufficient to drive centrosomal localization and simultaneously abrogate centromeric association of corresponding Sgo1 isoforms. Cohesin is shown to be a target of the prophase pathway at centrosomes and protected by Sgo1-PP2A. Accordingly, premature centriole disengagement in response to Sgo1 depletion is suppressed by blocking ring opening of an engineered cohesin.

  11. Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines

    Directory of Open Access Journals (Sweden)

    Travert Carine

    2010-10-01

    Full Text Available Abstract Background Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. Methods The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. Results All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%. CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Conclusion Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a

  12. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

    Directory of Open Access Journals (Sweden)

    Valentina Marcellini

    2017-09-01

    Full Text Available Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies.

  13. Cognitive Reserve Protects Against Apathy in Individuals with Human Immunodeficiency Virus

    Science.gov (United States)

    Shapiro, Miriam E.; Mahoney, Jeannette R.; Peyser, Deena; Zingman, Barry S.; Verghese, Joe

    2014-01-01

    Apathy is associated with impaired neuropsychological functioning in individuals with HIV. While cognitive reserve (CR) delays neurocognitive decline, CR's relationship with apathy has never been studied. We examined CR's association with apathy in 116 HIV-positive individuals recruited from an urban AIDS center and assessed whether this relationship is moderated by age and/or disease severity. Participants completed the Wechsler Test of Adult Reading and Apathy Evaluation Scale. A CR-composite, combining years of education and word-reading ability, significantly predicted apathy (t = −2.37, p = .02). CR's relationship with apathy was not moderated by age, but participants with nadir CD4 levels ≤200 demonstrated a stronger association (t = −3.25, p = .002) than those with nadir CD4 levels > 200 (t = −0.61, p = .55). These findings suggest a protective effect of CR against apathy in HIV-infected individuals across the age span, particularly after a certain threshold of disease severity. PMID:24021844

  14. Media representations of early human development: protecting, feeding and loving the developing brain.

    Science.gov (United States)

    O'Connor, Cliodhna; Joffe, Helene

    2013-11-01

    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Mussel oligopeptides protect human fibroblasts from hydrogen peroxide (H2O2)-induced premature senescence.

    Science.gov (United States)

    Zhou, Yue; Dong, Ying; Xu, Qing-Gang; Zhu, Shu-Yun; Tian, Shi-Lei; Huo, Jing-jing; Hao, Ting-Ting; Zhu, Bei-Wei

    2014-01-01

    Mussel bioactive peptides have been viewed as mediators to maximize the high quality of life. In this study, the anti-aging activities of mussel oligopeptides were evaluated using H2O2-induced prematurely senescent MRC-5 fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry displayed that exposure to H2O2 led to the loss of cell viability and cell cycle arrest. In addition, H2O2 caused the elevation of senescence-associated-β-galactosidase (SA-β-gal) activity and formation of senescence-associated heterochromatin foci (SAHF). It was found that pretreatment with mussel oligopeptides could significantly attenuate these properties associated with cellular senescence. Mussel oligopeptides also led to the increase of glutathione (GSH) level and mitochondrial transmembrane potential (Δψm) recovery. In addition, mussel oligopeptides resulted in an improvement in transcriptional activity of peroxiredoxin 1 (Prx1), nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin 1 (SIRT1). This study revealed that mussel oligopeptides could protect against cellular senescence induced by H2O2, and the effects were closely associated with redox cycle modulating and potentiating the SIRT1 pathway. These findings provide new insights into the beneficial role of mussel bioactive peptides on retarding senescence process. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  16. The protection of fundamental human rights in criminal process
    General report

    Directory of Open Access Journals (Sweden)

    Chrisje Brants

    2009-10-01

    Full Text Available This contribution examines the effect of the uniform standards of human rights in international conventions on criminal process in different countries and identifies factors inherent in national systems that influence the scope of international standards and the way in which they are implemented in a national context. Three overreaching issues influence the reception of international fundamental rights and freedoms in criminal process: constitutional arrangements, legal tradition and culture, and practical circumstances. There is no such thing as the uniform implementation of convention standards; even in Europe where the European Convention on Human Rights and Fundamental Freedoms and the case law of the European Court play a significant role, there is still much diversity in the actual implementation of international norms due to the influence of legal traditions which form a counterforce to the weight of convention obligations. An even greater counterforce is at work in practical circumstances that can undermine international norms, most especially global issues of security, crime control and combating terrorism. Although convention norms are still in place, there is a very real risk that they are circumvented or at least diluted in order to increase effective crime control.

  17. Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC).

    Science.gov (United States)

    Song, Juxian; Li, Yiqing; Ge, Jian; Duan, Yongheng; Sze, Stephen Cho-Wing; Tong, Yao; Shaw, Pang-Chui; Ng, Tzi-Bun; Tsui, Kam Chuen; Zhuo, Yehong; Zhang, Kalin Yanbo

    2010-04-01

    The use of bilberry (Vaccinium myrtillus L.) as a food and medicine for improving human vision has a long history all over the world. However, there is lack of convincing evidence from rigorous clinical trials or scientific research. This study investigated the effects of different concentrations of bilberry extracts on the cell viability, cell cycle and the expression of hyaluronic acid and glycosaminoglycans of cultured human corneal limbal epithelial cells. The data showed that bilberry extracts had no cytotoxicity to the corneal limbal epithelial cells at a wide range of concentrations (10(-9)-10(-4) M, equalized to the content of cyanidin-3-O-glucoside). Bilberry extract (10(-6), 10(-5) and 10(-4) M) increased cell viability after 48 h incubation. The number of cells decreased in G(0)/G(1) phase and increased prominently in S and G(2)/M phases after treatment with bilberry extracts at a high concentration (10(-4) M). The expression of glycosaminoglycans increased prominently after incubation with bilberry extracts (10(-7) and 10(-4) M) for 48 h while no significant changes were observed for the expression of hyaluronic acid. The results indicated that bilberry extract may be beneficial for the physiological renewal and homeostasis of corneal epithelial cells. Copyright (c) 2010 John Wiley & Sons, Ltd.

  18. Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection.

    Science.gov (United States)

    Qiu, Hongjie; Sun, Shihui; Xiao, He; Feng, Jiannan; Guo, Yan; Tai, Wanbo; Wang, Yufei; Du, Lanying; Zhao, Guangyu; Zhou, Yusen

    2016-08-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Shterzer, Naama; Heyman, Dariya; Shapiro, Beny; Yaniv, Abraham; Jackman, Anna [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Serour, Francis [Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon (Israel); Chaouat, Malka [Laboratory of Experimental Surgery, Hadassah University Hospital, Ein Karem, Jerusalem (Israel); Gonen, Pinhas [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Tommasino, Massimo [International Agency for Research on Cancer, World Health Organization, Lyon (France); Sherman, Levana [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-11-15

    In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling.

  20. Cytoplasmic PELP1 and ERRgamma protect human mammary epithelial cells from Tam-induced cell death.

    Science.gov (United States)

    Girard, Brian J; Regan Anderson, Tarah M; Welch, Siya Lem; Nicely, Julie; Seewaldt, Victoria L; Ostrander, Julie H

    2015-01-01

    Tamoxifen (Tam) is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+) breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1) promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples. In vitro, immortalized HMECs expressing a nuclear localization signal (NLS) mutant of PELP1 (PELP1-cyto) were resistant to Tam-induced death. Furthermore, PELP1-cyto signaling through estrogen-related receptor gamma (ERRγ) promoted cell survival in the presence of Tam. Overexpression of ERRγ in immortalized HMECs protected cells from Tam-induced death, while knockdown of ERRγ sensitized PELP1-cyto expressing HMECs to Tam. Moreover, Tam-induced HMEC cell death was independent of apoptosis and involved accumulation of the autophagy marker LC3-II. Expression of PELP1-cyto and ERRγ reduced Tam-induced LC3-II accumulation, and knockdown of ERRγ increased LC3-II levels in response to Tam. Additionally, PELP1-cyto expression led to the upregulation of MMP-3 and MAOB, known PELP1 and ERRγ target genes, respectively. Our data indicate that cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of Tam. These data suggest that PELP1 localization and/or ERRγ activation could be developed as tissue biomarkers for Tam responsiveness.

  1. Cytoplasmic PELP1 and ERRgamma protect human mammary epithelial cells from Tam-induced cell death.

    Directory of Open Access Journals (Sweden)

    Brian J Girard

    Full Text Available Tamoxifen (Tam is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+ breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1 promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples. In vitro, immortalized HMECs expressing a nuclear localization signal (NLS mutant of PELP1 (PELP1-cyto were resistant to Tam-induced death. Furthermore, PELP1-cyto signaling through estrogen-related receptor gamma (ERRγ promoted cell survival in the presence of Tam. Overexpression of ERRγ in immortalized HMECs protected cells from Tam-induced death, while knockdown of ERRγ sensitized PELP1-cyto expressing HMECs to Tam. Moreover, Tam-induced HMEC cell death was independent of apoptosis and involved accumulation of the autophagy marker LC3-II. Expression of PELP1-cyto and ERRγ reduced Tam-induced LC3-II accumulation, and knockdown of ERRγ increased LC3-II levels in response to Tam. Additionally, PELP1-cyto expression led to the upregulation of MMP-3 and MAOB, known PELP1 and ERRγ target genes, respectively. Our data indicate that cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of Tam. These data suggest that PELP1 localization and/or ERRγ activation could be developed as tissue biomarkers for Tam responsiveness.

  2. SIRT1 Protects Human Lens Epithelial Cells Against Oxidative Stress by Inhibiting p53-Dependent Apoptosis.

    Science.gov (United States)

    Zheng, Tianyu; Lu, Yi

    2016-08-01

    This study aims to test the hypothesis that sirtuin type 1 (SIRT1) plays a role in modulating resistance against oxidative stress in lens epithelial cells (LECs), and to determine its mechanism if this hypothesis is found to be true. Cultured LECs were treated with resveratrol (RES, an activator of SIRT1) or nicotinamide (NAM, a SIRT1 inhibitor) and incubated with H2O2. Changes in SIRT1, p53, and acetyl-p53 expressions were measured. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. TUNEL assay was used to evaluate apoptosis. Pifithrin-α (PFT-α) was applied to block the p53 pathway. SIRT1 expressions significantly increased with H2O2 treatment and further increased with RES treatment in a dose-dependent manner. RES eliminated cellular morphological changes related to H2O2 treatment, increased cell proliferation, and inhibited apoptosis under oxidative stress. In contrast, NAM enhanced cell apoptosis under oxidative stress and decreased cell proliferation. RES caused a dose-dependent decrease in acetyl-p53 levels under oxidative stress, while NAM increased p53 acetylation. Under oxidative conditions, PFT-α, a p53 pathway inhibitor, eliminated the destructive effect of NAM. PFT-α decreased the morphological changes in LECs compared to NAM treatment and increased cell proliferation and inhibited apoptosis. SIRT1 protected LECs from oxidative stress via the inhibition of the p53 pathway. SIRT1 or SIRT1 activators could potentially be used to prevent ocular aging and cataract in the future.

  3. NINE KEY FUNCTIONS FOR A HUMAN SUBJECTS PROTECTION PROGRAM FOR COMMUNITY-ENGAGED RESEARCH: POINTS TO CONSIDER1

    Science.gov (United States)

    Ross, Lainie Friedman; Loup, Allan; Nelson, Robert M.; Botkin, Jeffrey R.; Kost, Rhonda; Smith, George R.; Gehlert, Sarah

    2010-01-01

    The Ethical Conduct of Community-engaged research (CEnR), of which the Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion, requires an integrated and comprehensive human subjects protection (HSP) program that addresses the additional concerns salient to CEnR where members of a community are both research partners and participants. As delineated in the federal regulations, the backbone of a HSP program is the fulfillment of nine functions: (1) minimize risks; (2) reasonable benefit-risk ratio; (3) fair subject selection; (4) adequate monitoring; (5) informed consent; (6) privacy and confidentiality; (7) conflicts of interest; (8) address vulnerabilities; and (9) HSP training. The federal regulations, however, do not consider the risks and harms that may occur to groups, and these risks have not traditionally been included in the benefit: risk analysis nor have they been incorporated into an HSP framework. We explore additional HSP issues raised by CEnR within these nine ethical functions. Various entities exist that can provide HSP—the investigator, the Institutional Review Board, the Conflict of Interest Committee, the Research Ethics Consultation program, the Research Subject Advocacy program, the Data and Safety Monitoring Plan, and the Community Advisory Board. Protection is best achieved if these entities are coordinated to ensure that no gaps exist, to minimize unnecessary redundancy, and to provide checks and balances between the different entities of HSP and the nine functions that they must realize. The document is structured to provide a “points-to-consider” roadmap for HSP entities to help them adequately address the nine key functions necessary to provide adequate protection of individuals and communities in CEnR. PMID:20235862

  4. ACTIVITIES OF THE ADMINISTRATION OF FEDERAL SERVICE FOR SURVEILLANCE ON CONSUMER RIGHTS PROTECTION AND HUMAN WELL-BEING IN KHABAROVSKY KRAI IN CONDITIONS OF THE FUKUSHIMA ACCIDENT AND MEASURES UNDERTAKEN TO PROTECT THE TERRITORY AND POPULATION THE REGION

    Directory of Open Access Journals (Sweden)

    V. A. Ott

    2011-01-01

    Full Text Available The article analyzes activities of the Administration of Federal Service for Surveillance on Consumer Rights Protection and Human Well-being in Khabarovsky Krai and the Federal Health Organization "Center of Hygiene and Epidemiology in Khabarovsky Krai" in the situation related to the Fukushima accident in Japan

  5. DNA and Law Enforcement in the European Union: Tools and Human Rights Protection

    Directory of Open Access Journals (Sweden)

    Helena Soleto Muñoz

    2014-01-01

    Full Text Available Since its first successful use in criminal investigations in the 1980s, DNA has become a widely used and valuable tool to identify offenders and to acquit innocent persons. For a more beneficial use of the DNA-related data possessed, the Council of the European Union adopted Council Decisions 2008/615 and 2008/616 establishing a mechanism for a direct automated search in national EU Member States’ DNA databases. The article reveals the complications associated with the regulation on the use of DNA for criminal investigations as it is regulated by both EU and national legislation which results in a great deal of variations. It also analyses possible violations of and limitations to human rights when collecting DNA samples, as well as their analysis, use and storage.

  6. Filling knowledge gaps in radiation protection methodologies for non-human biota. Final summary report

    Energy Technology Data Exchange (ETDEWEB)

    Brown, J.; Gjelsvik, R. (Norwegian Radiation Protection Authority (Norway)); Holm, E. (Univ. of Lund (Sweden)); Roos, P. (Technical Univ. of Denmark, Risoe National Lab. for Sustainable Energy, Roskilde (Denmark)); Saxen, R.; Outola, I. (Radiation and Nuclear Safety Authority (Finland))

    2009-03-15

    The activities of the GAPRAD project are summarised in this report. The background and rationale to GAPRAD are presented and explained. Most notably this relates to a lack of information on naturally occuring radionuclides in terrestrial and aquatic systems that have direct applicability for use in environmental impact assessments. Results from field activities are presented from the Dovrefjell area in Norway (terrestrial study) and selected lake and brackish water systems in Finland. The data mainly concern activity concentrations of Po-210 in environmental media and selected biota allowing concentration ratios to be derived where appropriate. Furthermore, details in relation to Po-210 uptake and biokinetics in humans based on experimental work conducted within the project are presented. (au)

  7. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

    Science.gov (United States)

    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  8. Aqueous extract of Crataegus azarolus protects against DNA damage in human lymphoblast Cell K562 and enhances antioxidant activity.

    Science.gov (United States)

    Mustapha, Nadia; Bouhlel, Inès; Chaabane, Fadwa; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2014-02-01

    The present study was carried out to characterize the cellular antioxidant effect of the aqueous extract of Crataegus azarolus and its antigenotoxic potential using human myelogenous cells, K562. The antioxidant capacity of this extract was evaluated by determining its cellular antioxidant activity (CAA) in K562 cells. Also, preceding antigenotoxicity assessment, its eventual genotoxicity property was investigated by evaluating its capacity to induce the DNA degradation of treated cell nuclei. As no genotoxicity was detected at different exposure times, its ability to protect cell DNA against H2O2 oxidative effect was investigated, using the "comet assay." It appears that 800 μg/mL of extract inhibited the genotoxicity induced by H2O2 with a rate of 41.30 %, after 4 h of incubation. In addition, this extract revealed a significant cellular antioxidant capacity against the reactive oxygen species in K562 cells.

  9. Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon.

    Directory of Open Access Journals (Sweden)

    R Cassel

    Full Text Available Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs may impair beta cell function and mass (lipotoxicity. Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics, respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.

  10. Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

    Science.gov (United States)

    Rithidech, Kanokporn Noy; Tungjai, Montree; Whorton, Elbert B.

    2005-01-01

    The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

  11. NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells.

    Directory of Open Access Journals (Sweden)

    Altaf H Sarker

    Full Text Available Secondhand smoke (SHS is a confirmed lung carcinogen that introduces thousands of toxic chemicals into the lungs. SHS contains chemicals that have been implicated in causing oxidative DNA damage in the airway epithelium. Although DNA repair is considered a key defensive mechanism against various environmental attacks, such as cigarette smoking, the associations of individual repair enzymes with susceptibility to lung cancer are largely unknown. This study investigated the role of NEIL2, a DNA glycosylase excising oxidative base lesions, in human lung cells treated with sidestream smoke (SSS, the main component of SHS. To do so, we generated NEIL2 knockdown cells using siRNA-technology and exposed them to SSS-laden medium. Representative SSS chemical compounds in the medium were analyzed by mass spectrometry. An increased production of reactive oxygen species (ROS in SSS-exposed cells was detected through the fluorescent detection and the induction of HIF-1α. The long amplicon-quantitative PCR (LA-QPCR assay detected significant dose-dependent increases of oxidative DNA damage in the HPRT gene of cultured human pulmonary fibroblasts (hPF and BEAS-2B epithelial cells exposed to SSS for 24 h. These data suggest that SSS exposure increased oxidative stress, which could contribute to SSS-mediated toxicity. siRNA knockdown of NEIL2 in hPF and HEK 293 cells exposed to SSS for 24 h resulted in significantly more oxidative DNA damage in HPRT and POLB than in cells with control siRNA. Taken together, our data strongly suggest that decreased repair of oxidative DNA base lesions due to an impaired NEIL2 expression in non-smokers exposed to SSS would lead to accumulation of mutations in genomic DNA of lung cells over time, thus contributing to the onset of SSS-induced lung cancer.

  12. Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure.

    Science.gov (United States)

    Aiyegbo, Mohammed S; Shmelkov, Evgeny; Dominguez, Lorenzo; Goger, Michael; Battacharya, Shibani; deCamp, Allan C; Gilbert, Peter B; Berman, Phillip W; Cardozo, Timothy

    2017-01-01

    The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α-helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α-helical conformations are preferred by this segment almost universally across all subtypes. Notably, α-helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α-helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α-helical peptide epitope in the V2 loop of HIV's surface envelope glycoprotein.

  13. Salidroside protects against homocysteine-induced injury in human umbilical vein endothelial cells via the regulation of endoplasmic reticulum stress.

    Science.gov (United States)

    Zhu, Lin; Jia, Fang; Wei, Jiang; Yu, Yang; Yu, Tianhong; Wang, Yanjun; Sun, Jianhui; Luo, Guanghua

    2017-02-01

    Previous studies showed that homocysteine (Hcy) could injure vascular endothelial cells via several mechanisms, including its promotion of oxidative stress pathway and endoplasmic reticulum stress (ER stress) pathway. Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. Emerging evidence conformed that SAL attenuated Hcy-induced endothelial dysfunction by reducing oxidative stress. However, its role in ER stress pathway remains unclarified. The purpose of this study was to explore the mechanism of the protective effect of SAL on Hcy-induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cell damage effects brought by Hcy in a dose-dependent manner. Functional studies on the HUVECs found that SAL rescued the endoplasmic reticulum stress induced by Hcy. The underlying mechanisms involve the inhibition of Hcy-induced activation of binding protein (Bip) and C/EBP homologous protein (CHOP), as well as the phosphorylation of protein kinase RNA-like ER kinase (PERK) or inositol-requiring enzyme 1 alpha (IRE1α). Taken together, these findings implicate that SAL could regulate ER stress pathway on the viability of endotheliocyte induced by Hcy in vitro. Our findings provide the first evidence that SAL plays an important role in endotheliocyte protection via suppressing ER stress pathway in HUVEC cells and that it may be a promising therapeutic target for atherosclerosis and cardiovascular disease. © 2016 John Wiley & Sons Ltd.

  14. The Impact of Environmental Design on Doffing Personal Protective Equipment in a Healthcare Environment: A Formative Human Factors Trial.

    Science.gov (United States)

    Herlihey, Tracey A; Gelmi, Stefano; Cafazzo, Joseph A; Hall, Trevor N T

    2017-06-01

    OBJECTIVE To explore the impact of environmental design on doffing personal protective equipment in a simulated healthcare environment. METHODS A mixed-methods approach was used that included human-factors usability testing and qualitative questionnaire responses. A patient room and connecting anteroom were constructed for testing purposes. This experimental doffing area was designed to overcome the environmental failures identified in a previous study and was not constructed based on any generalizable hospital standard. RESULTS In total, 72 healthcare workers from Ontario, Canada, took part in the study and tested the simulated doffing area. The following environmental design changes were tested and were deemed effective: increasing prominence of color-coded zones; securing disinfectant wipes and hand sanitizer; outlining disposal bins locations; providing mirrors to detect possible contamination; providing hand rails to assist with doffing; and restricting the space to doff. Further experimentation and iterative design are required with regard to several important features: positioning the disposal bins for safety, decreasing the risk of contamination and user accessibility; optimal positioning of mirrors for safety; communication within the team; and positioning the secondary team member for optimal awareness. Additional design suggestions also emerged during this study, and they require future investigation. CONCLUSIONS This study highlights the importance of the environment on doffing personal protective equipment in a healthcare setting. Iterative testing and modification of the design of the environment (doffing area) are important to enhancing healthcare worker safety. Infect Control Hosp Epidemiol 2017;38:712-717.

  15. In Vitro Protective Effects of Lycium barbarum Berries Cultivated in Umbria (Italy on Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    M. R. Ceccarini

    2016-01-01

    Full Text Available Lycium barbarum is a famous plant in the traditional Chinese medicine. The plant is known to have health-promoting bioactive components. The properties of Lycium barbarum berries cultivated in Umbria (Italy and their effect on human hepatocellular carcinoma cells (HepG2 have been investigated in this work. The obtained results demonstrated that the Lycium barbarum berries from Umbria region display high antioxidant properties evaluated by total phenolic content and ORAC method, on hydrophilic and lipophilic fractions. Moreover, on HepG2 cell line Lycium barbarum berries extract did not change cell viability analyzed by MTT and Trypan blue exclusion assay and did not induce genotoxic effect analyzed by comet assay. Furthermore, it was demonstrated, for the first time, that the berries extract showed a protective effect on DNA damage, expressed as antigenotoxic activity in vitro. Finally, Lycium barbarum berries extract was able to modulate the expression of genes involved in oxidative stress, proliferation, apoptosis, and cancer. In particular, downexpression of genes involved in tumor migration and invasion (CCL5, in increased risk of metastasis and antiapoptotic signal (DUSP1, and in carcinogenesis (GPx-3 and PTGS1, together with overexpression of tumor suppressor gene (MT3, suggested that Umbrian Lycium barbarum berries could play a protective role against hepatocellular carcinoma.

  16. Synergistic Application of Black Tea Extracts and Lactic Acid Bacteria in Protecting Human Colonocytes against Oxidative Damage.

    Science.gov (United States)

    Zhao, Danyue; Shah, Nagendra P

    2016-03-23

    In view of the potential of lactic acid bacteria (LAB) to enhance the antioxidant activity of food products, this work explored the effectiveness of LAB fermented black tea samples in alleviating H2O2-induced oxidative stress in human colonocytes. The antioxidant capacity of tea samples was evaluated in terms of cyto-protectiveness, mitochondria membrane potential (Δψm)-stabilizing activity, ROS-inhibitory effect, and antioxidant enzyme-modulating activity. The effect on oxidative DNA damage and repair was studied in CCD 841 by comet assay. Results showed that the protective effect of tea pretreatment was more pronounced in normal cells (CCD 841) than in carcinomas (Caco-2), and fermented samples were invariably more effective. Higher cell viability and Δψm were maintained and ROS production was markedly inhibited with tea pretreatment. The fermented tea samples also remarkably stimulated DNA repair, resulting in fewer strand breaks and oxidative lesions. Our study implied that LAB fermentation may be an efficient way to enhance the antioxidative effectiveness of black tea flavonoid-enriched foods.

  17. Naringin Protects Against High Glucose-Induced Human Endothelial Cell Injury Via Antioxidation and CX3CL1 Downregulation

    Directory of Open Access Journals (Sweden)

    Guilin Li

    2017-08-01

    Full Text Available Background/Aims: The induction of endothelial injury by hyperglycemia in diabetes has been widely accepted. Naringin is a bio-flavonoid. Some studies showed that naringin alleviates diabetic complications, but the exact mechanisms by which naringin improves diabetic anomalies are not yet fully understood. The aim of this research was to study the protective effect of naringin on high glucose-induced injury of human umbilical vein endothelial cells (HUVECs. Methods: HUVECs were cultured with or without high glucose in the absence or presence of naringin for 5 days. The expression of CX3CL1 was determined by quantitative real-time RT-PCR (qPCR and western blot. The cellular bioenergetic analysis oxygen consumption rate (OCR was measured with a Seahorse Bioscience XF analyzer. Results: The production of reactive oxygen species (ROS, the expression of CX3CL1 and the level of AKT phosphorylation were increased in HUVECs cultured with high glucose compared with controls. However, naringin rescued these increases in ROS production, CX3CL1 expression and AKT phosphorylation. Nitric oxide (NO production and OCR were lower in the high glucose group, and naringin restored the changes induced by high glucose. Molecular docking results suggested that Naringin might interact with the CX3CL1 protein. Conclusion: Naringin protects HUVECs from high-glucose-induced damage through its antioxidant properties by downregulating CX3CL1 and by improving mitochondrial function.

  18. Recombinant AAV-mediated expression of human BDNF protects neurons against cell apoptosis in Abeta-induced neuronal damage model.

    Science.gov (United States)

    Liu, Zhaohui; Ma, Dongliang; Feng, Gaifeng; Ma, Yanbing; Hu, Haitao

    2007-06-01

    The human brain-derived neurotrophic factor (hBDNF) gene was cloned by polymerase chain reaction and the recombinant adeno-associated viral vector inserted with hBDNF gene (AAV-hBDNF) was constructed. Cultured rat hippocampal neurons were treated with Abeta(25-35) and serued as the experimental Abeta-induced neuronal damage model (AD model), and the AD model was infected with AAV-hBDNF to explore neuroprotective effects of expression of BDNF. Cell viability was assayed by MTT. The expression of bcl-2 anti-apoptosis protein was detected by immunocytochemical staining. The change of intracellular free Ca ion ([Ca2+]i) was measured by laser scanning confocal microscopy. The results showed that BDNF had protective effects against A-induced neuronal damage. The expression of the bcl-2 anti-apoptosis protein was raised significantly and the balance of [Ca2+]i was maintained in the AAv-hBDNF treatment group as compared with AD model group. These data suggested that recombinant AAV mediated a stable expression of hBDNF in cultured hippocampal neurons and resulted in significant neuron protective effects in AD model. The BDNF may reduce neuron apoptosis through increasing the expression of the bcl-2 anti-apoptosis protein and inhibiting intracellular calcium overload. The viral vector-mediated gene expression of BDNF may pave the way of a novel therapeutic strategy for the treatment of neurodegenerative diseases such as Alzheimer's disease.

  19. Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture.

    Science.gov (United States)

    Miller-Pinsler, Lutfiya; Wells, Peter G

    2015-09-15

    Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat(b)/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug=GD 1), exposed for 24h to 2 or 4mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (pcatalase (PEG-cat) 8h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (pcatalase is a determinant of risk for EtOH embryopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress

    Directory of Open Access Journals (Sweden)

    Dan eLi

    2015-07-01

    Full Text Available This study aims to investigate if histo-blood group antigen (HBGA expressing bacteria have any protective role on human norovirus (NoV from acute heat stress. Eleven bacterial strains were included, belonging to Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Clostridium difficile, Bifidobacterium adolescentis, and Bifidobacterium longum. HBGA expression of the bacteria as well as binding of human NoV virus-like particles (VLPs, GI.1 and GII.4 strains to the bacteria were detected by flow cytometry. NoV VLPs pre-incubated with HBGA expressing or non-HBGA expressing bacteria were heated and detected by both direct ELISA and porcine gastric mucin-binding assay. The NoV-binding abilities of the bacteria correlated well with their HBGA expression profiles. Two HBGA expressing E.coli (LMG8223 and LFMFP861, both GI.1 and GII.4 binders and one non-HBGA expressing E.coli (ATCC8739, neither GI.1 nor GII.4 binder were selected for the heat treatment test with NoV VLPs. Compared with the same cell numbers of non-HBGA expressing E.coli, the presence of HBGA-expressing E.coli could always maintain higher antigen integrity, as well as mucin-binding ability of NoV VLPs of both GI.1 and GII.4 after heat-treatment at 90°C for 2 min. These results indicate that HBGA-expressing bacteria may protect NoVs during the food processing treatments, thereby facilitating their transmission.

  1. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  2. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  3. Protective effect of recombinant human erythropoietin on liver and kidney injury as well as endoplasmic reticulum stress caused by infec

    Directory of Open Access Journals (Sweden)

    Yan-Li Jiang

    2016-03-01

    Full Text Available Objective: To study the protective effect of recombinant human erythropoietin on liver and kidney injury as well as endoplasmic reticulum stress caused by infection. Methods: Male Wistar rats were randomly divided into negative control group, LPS group and LPS+EPO group, LPS group and LPS+EPO group received injection of LPS via caudal vein to establish infection models, and LPS+EPO group received injection of rHuEPO via caudal vein for intervention; before intervention as well as 6 and 12 h after intervention, serum was collected to detect TNF-α, iNOS, BUN, Cr, ALT and AST contents; 12 h after intervention, liver and kidney tissue was collected to detect mRNA contents of endoplasmic reticulum stress molecules (GRP78, CHOP and Caspase-12. Results: After model establishment and before rHuEPO intervention, serum TNF-α, iNOS, BUN, Cr, ALT and AST contents of LPS group and LPS+EPO group had no differences and were higher than those of negative control group; 6 and 12 h after intervention, serum TNF-α, iNOS, BUN, Cr, ALT and AST contents of LPS+EPO group were lower than those of LPS group; 12 h after intervention, mRNA contents of GRP78, CHOP and Caspase-12 in liver and kidney tissue of LPS+EPO group were lower than those of LPS group. Conclusions: Recombinant human erythropoietin has protective effect on liver and kidney injury as well as endoplasmic reticulum stress caused by infection.

  4. Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir.

    Science.gov (United States)

    Ren, Huanhuan; Wang, Guiqin; Wang, Shuangshuang; Chen, Honglin; Chen, Zhiwei; Hu, Hongxing; Cheng, Genhong; Zhou, Paul

    2016-01-01

    Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted.

  5. Dimethylfumarate protects against TNF-α-induced secretion of inflammatory cytokines in human endothelial cells.

    Science.gov (United States)

    Gerhardt, Simon; König, Veronika; Doll, Monika; Hailemariam-Jahn, Tsige; Hrgovic, Igor; Zöller, Nadja; Kaufmann, Roland; Kippenberger, Stefan; Meissner, Markus

    2015-01-01

    Inflammation, angiogenesis and oxidative stress have been implicated in the pathogenesis of various vascular diseases. Recent evidence suggests that dimethylfumarate (DMF), an antiposriatic and anti-multiple sclerosis agent, possesses anti-inflammatory, anti-oxidative and anti-angiogenic properties. Here, we analyze the influence of DMF on TNF-α-induced expression of the important pro-inflammatory and pro-atherogenic chemokine MCP-1 and investigate the underlying mechanisms of this expression. We analyzed constitutive and TNF-α-induced expression of MCP-1 in human umbilical vascular endothelial cells (HUVEC) +/- DMF treatment via enzyme-linkes immunosorbent assay (ELISA). DMF significantly inhibited the protein expression levels in a time- and concentration-dependent manner. Furthermore, MCP-1 mRNA expression was also reduced in response to DMF, as demonstrated by RT-PCR. Thus, the regulation occurs at the transcriptional level. Interestingly, DMF prolonged the TNF-α-induced p38 and JNK phosphorylation in HUVEC, as demonstrated by Western blot analysis; however, the p38 and JNK inhibitor SB203580 did not affect the DMF-conveyed suppression of TNF-α-induced MCP-1 expression. DMF suppressed the TNF-α-induced nuclear translocation and phosphorylation (Serine 536) of p65 in these cells. These results were additionally approved by p65 luciferase promoter assays. Furthermore, we found that DMF slightly inhibited the early degradation of IκBα. In addition, we verified our results using other important inflammatory cytokines such as CCL-5, PDGF-BB, GM-CSF and IL-6. DMF suppresses various TNF-α-induced pro-inflammatory and pro-atherogenic cytokines/chemokines in human endothelial cells. This action is regulated by reduced p65 activity and nuclear translocation, which can be explained in part by the reduced early degradation of IκBα and more important the reduced phosphorylation of p65 at Serine 536. These effects were independent of the p38, PI3K and p42

  6. The human resource implications of improving financial risk protection for mothers and newborns in Zimbabwe.

    Science.gov (United States)

    Chirwa, Yotamu; Witter, Sophie; Munjoma, Malvern; Mashange, Wilson; Ensor, Tim; McPake, Barbara; Munyati, Shungu

    2013-05-28

    A paradigm shift in global health policy on user fees has been evident in the last decade with a growing consensus that user fees undermine equitable access to essential health care in many low and middle income countries. Changes to fees have major implications for human resources for health (HRH), though the linkages are rarely explicitly examined. This study aimed to examine the inter-linkages in Zimbabwe in order to generate lessons for HRH and fee policies, with particular respect to reproductive, maternal and newborn health (RMNH). The study used secondary data and small-scale qualitative fieldwork (key informant interview and focus group discussions) at national level and in one district in 2011. The past decades have seen a shift in the burden of payments onto households. Implementation of the complex rules on exemptions is patchy and confused. RMNH services are seen as hard for families to afford, even in the absence of complications. Human resources are constrained in managing current demand and any growth in demand by high external and internal migration, and low remuneration, amongst other factors. We find that nurses and midwives are evenly distributed across the country (at least in the public sector), though doctors are not. This means that for four provinces, there are not enough doctors to provide more complex care, and only three provinces could provide cover in the event of all deliveries taking place in facilities. This analysis suggests that there is a strong case for reducing the financial burden on clients of RMNH services and also a pressing need to improve the terms and conditions of key health staff. Numbers need to grow, and distribution is also a challenge, suggesting the need for differentiated policies in relation to rural areas, especially for doctors and specialists. The management of user fees should also be reviewed, particularly for non-Ministry facilities, which do not retain their revenues, and receive limited investment in

  7. Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on Psoriasis Susceptibility

    Science.gov (United States)

    Lai, Olivia Y.; Chen, Haoyan; Michaud, Henri-Alexandre; Hayashi, Genki; Kuebler, Peter J.; Hultman, Gustaf K.; Ariza, Maria-Eugenia; Williams, Marshall V.; Batista, Mariana D.; Nixon, Douglas F.; Foerster, John; Bowcock, Anne M.; Liao, Wilson

    2012-01-01

    Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the MHC region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense SNP rs3134774 (K158R, p=3.28 × 10-15, OR=2.36 [1.91-2.92]). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared to controls (pT-cell responses against a single HERV-K dUTPase peptide (ppsoriasis susceptibility, and suggest the need for additional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis. PMID:22437317

  8. Los Alamos Science: Number 23, 1995. Radiation protection and the human radiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, N.G. [ed.

    1995-12-31

    There are a variety of myths and misconceptions about the ionizing radiation that surrounds and penetrates us all. Dispel a few of these by taking a leisurely tour of radiation and its properties, of the natural and man-made sources of ionizing radiation, and of the way doses are calculated. By damaging DNA and inducing genetic mutations, ionizing radiation can potentially initiate a cell on the road to cancer. The authors review what is currently known about regulation of cellular reproduction, DNA damage and repair, cellular defense mechanisms, and the specific cancer-causing genes that are susceptible to ionizing radiation. A rapid survey of the data on radiation effects in humans shows that high radiation doses increase the risk of cancer, whereas the effects of low doses are very difficult to detect. The hypothetical risks at low doses, which are estimated from the atomic-bomb survivors, are compared to the low-dose data so that the reader can assess the present level of uncertainty. As part of the openness initiative, ten individuals who have worked with plutonium during various periods in the Laboratory`s history were asked to share their experiences including their accidental intakes. The history and prognosis of people who have had plutonium exposures is discussed by the Laboratory`s leading epidemiologist.

  9. Protective effects of antioxidants on high Glucose-induced malfunctions in human glomerular mesangial cells

    Directory of Open Access Journals (Sweden)

    Hosseini R

    2000-08-01

    Full Text Available Altered functions of mesangial cells induced by high glucose concentrations are thought to play an important role in the pathogenesis of diabetic nephropathy. We therefore investigated the effect of high glucose (39.2 mM alone and in combination with taurine (500 µM or vitamin E (100 µM in serum free medium (RPMI 1640 on the proliferative growth response and turnover of type IV collagen by human glomerular mesangial cells (GMC. The results showed that the high glucose level decreases the proliferation of the GMC which is reversed by taurine and vitamin E. In order to control the osmotic effects of high glucose, the GMC were also cultured in the presence of manitol. Manitol had no effect on the proliferation of GMC. Furthermore, the results showed that addition of vitamin E or taurine to media containing high glucose could reverse and normalize the collagen turn-over by the cultured mesangial cells. These results suggest that taurie and vitamin E may function as endogenous agents in the kidney to limit the development of glomerulosclerosis in diabetic renal disease.

  10. Antioxidant Protection against Curative and Palliative Doses of Ionizing Irradiation in Human Blood Decreases with Aging

    Directory of Open Access Journals (Sweden)

    Jelena Kasapović

    2012-01-01

    Full Text Available Reactive oxygen species (ROS are independently recognized to play a significant role in radiation-induced damage on healthy tissue and in aging process. However, an age-related alteration of antioxidant (AO system in radiation response in humans is poorly investigated. The aim of this paper was to evaluate the irradiation effects on the activities and expression of AO system in the blood of healthy women during aging. Blood samples were irradiated with curative and palliative doses of 2 Gy or 9 Gy γ-rays. AO capacity for detoxification of O2•− and H2O2 in response to 2 Gy γ-irradiation decreases in women above 58 years, while in response to 9 Gy shows signs of weakening after 45 years of age. Due to reduction of AO capacity during aging, cytotoxic effects of curative and palliative doses of irradiation, mediated by ROS, may significantly increase in older subjects, while removal of H2O2 excess could reduce them.

  11. Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function

    Directory of Open Access Journals (Sweden)

    Ghaffari Mohammad Ali

    2016-07-01

    Full Text Available Background Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS. Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3, cadmium chloride (CdCl2, and lead chloride (PbCl4. Materials and Methods In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA production was assessed as a lipid peroxidation marker. Results Aluminum chloride (AlCl3, cadmium chloride (CdCl2, and lead chloride (PbCl4 diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm. Conclusion Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production.

  12. Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment, and Differentiation

    Directory of Open Access Journals (Sweden)

    Loriana Vitillo

    2016-08-01

    Full Text Available Human embryonic stem cells (hESCs can be maintained in a fully defined niche on extracellular matrix substrates, to which they attach through integrin receptors. However, the underlying integrin signaling mechanisms, and their contribution to hESC behavior, are largely unknown. Here, we show that focal adhesion kinase (FAK transduces integrin activation and supports hESC survival, substrate adhesion, and maintenance of the undifferentiated state. After inhibiting FAK kinase activity we show that hESCs undergo cell detachment-dependent apoptosis or differentiation. We also report deactivation of FAK downstream targets, AKT and MDM2, and upregulation of p53, all key players in hESC regulatory networks. Loss of integrin activity or FAK also induces cell aggregation, revealing a role in the cell-cell interactions of hESCs. This study provides insight into the integrin signaling cascade activated in hESCs and reveals in FAK a key player in the maintenance of hESC survival and undifferentiated state.

  13. Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function.

    Science.gov (United States)

    Jamalan, Mostafa; Ghaffari, Mohammad Ali; Hoseinzadeh, Pooneh; Hashemitabar, Mahmoud; Zeinali, Majid

    2016-01-01

    Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin) on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4). In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA) production was assessed as a lipid peroxidation marker. Aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4) diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm. Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production.

  14. Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function

    Science.gov (United States)

    Jamalan, Mostafa; Ghaffari, Mohammad Ali; Hoseinzadeh, Pooneh; Hashemitabar, Mahmoud; Zeinali, Majid

    2016-01-01

    Background Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin) on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4). Materials and Methods In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA) production was assessed as a lipid peroxidation marker. Results Aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4) diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm. Conclusion Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production. PMID:27441055

  15. The protection of salidroside on oxidative stress induced in human lens epithelium cells

    Directory of Open Access Journals (Sweden)

    Li-Ting Liu

    2017-10-01

    Full Text Available AIM: To explore the effect of different concentrations of salidroside on H2O2 induced oxidative stress damage in human lens epithelium cells(HLEC. METHODS: HLEC were cultured and divided into negative control group: cultured in normal cultivation; oxidative damage group: treated with 100μmol/L H2O2 for 12h; Salidroside low concentration group: 10μmol/L salidroside treated for 24h and H2O2 treated for 12h; Salidroside high concentration group: 100μmol/L salidroside treated for 24h and H2O2 treated for 12h. MTT method was applied to observe the effect of salidroside on HLEC survival rate. Morphological change of each group were observed and recorded under inverted microscope. DCFH-DA fluorescent probe was applied to detect intracellular ROS changes; content of malondialdehyde(MDA, superoxide dismutase(SODand glutathione peroxidase(GSH-Pxin supernatants were detected by pectrophotometer. RESULTS: Salidroside obviously inhibited H2O2-induced HLEC vitality decline, inhibited ROS generation in cells, causing SOD, GSH-Px levels increased and MDA levels decreased. CONCLUSION: Salidroside inhibited H2O2 induced HLEC injury by decreasing the intracellular MDA content levels and increasing SOD, GSH-Px content levels, which conclude that salidroside may have a certain role in the treatment of HLEC damage.

  16. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Ryan

    2017-04-01

    Full Text Available Human rotavirus (HRV is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10, which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040 that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB, which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043, which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the

  17. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea.

    Science.gov (United States)

    Nealon, Nora Jean; Yuan, Lijuan; Yang, Xingdong; Ryan, Elizabeth P

    2017-01-01

    Human rotavirus (HRV) is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB) did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro) alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum) in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10), which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040) that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB), which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043), which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the ability of HRV to

  18. Protective Effects of Extracts and Flavonoids Isolated from Scutia buxifolia Reissek against Chromosome Damage in Human Lymphocytes Exposed to Hydrogen Peroxide

    OpenAIRE

    Michel Mansur Machado; Ivana Beatrice Manica da Cruz; Margareth Linde Athayde; Luiz Filipe Machado; Olmiro de Souza Filho; Michele Rorato Sagrillo; Aline Augusti Boligon

    2012-01-01

    Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of crude extract, ethyl acetate fraction and flavonoids (quercetin, quercitrin, isoquercitrin and rutin) isolated from the leaves from Scutia buxifolia against chromosome damage induced by H2O2 in human lymphocytes by analyzing cellula...

  19. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2.

    Science.gov (United States)

    Hiby, Susan E; Apps, Richard; Sharkey, Andrew M; Farrell, Lydia E; Gardner, Lucy; Mulder, Arend; Claas, Frans H; Walker, James J; Redman, Christopher W; Redman, Christopher C; Morgan, Linda; Tower, Clare; Regan, Lesley; Moore, Gudrun E; Carrington, Mary; Moffett, Ashley

    2010-11-01

    Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells--specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells--influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2+ trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success.

  20. Monoclonal antibodies to the reactive centre loop (RCL) of human corticosteroid-binding globulin (CBG) can protect against proteolytic cleavage.

    Science.gov (United States)

    Lewis, John G; Elder, Peter A

    2017-07-01

    Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Microencapsulation-protected l-ascorbic acid for the application of human epithelial HaCaT cell proliferation.

    Science.gov (United States)

    Lam, P-L; Kok, S H-L; Bian, Z-X; Lam, K-H; Gambari, R; Lee, K K-H; Chui, C-H

    2014-01-01

    l-ascorbic acid is an abundant water-soluble nutrient found in vegetables and fruits. It enhances the cell proliferation, which is helpful in wound healing process. However, it is relatively unstable and easily degraded under external environments including acidity, alkalinity, evaporation, heat, oxidization, light or moisture. Its storage remains challenged. This study reported the development of l-ascorbic acid microcapsules using the natural protein, gelatin, and the natural polysaccharide, agar, as the wall protection carrier. The physical properties including entrapment efficiency, particle size, surface morphology, chemical compositions and release profile were identified. The cell proliferation of l-ascorbic acid microcapsules was stronger than the free drug. Significant cell growth in microencapsulated l-ascorbic acid-treated human epithelial HaCaT cells was observed when compared with untreated control. Since cell proliferation and wound repair are closely related, it is believed that l-ascorbic acid microcapsules would effectively increase the potential effect of wound healing activity in human skin.

  2. The procedure of involuntary hospitalization of persons with mental disorder in light of the human rights protection standards

    Directory of Open Access Journals (Sweden)

    Petrušić Nevena

    2007-01-01

    Full Text Available This paper is aimed at analyzing the procedure of involuntary hospitalization of persons with mental disorder. Considering the fact that enforced hospitalization interferes with the fundamental human rights and individual freedoms, the rules of involuntary hospitalization procedure have to provide for the legality of decisions, prevent possible abuses and enable the exercise of legitimate rights and interests of persons with mental disorder confined to treatment in psychiatric institutions. Bearing in mind the significance of the involuntary hospitalization procedure, the author of this paper provides a critical analysis of the national regulation on involuntary hospitalization. The aim of this analysis is to observe whether the rules of involuntary hospitalization procedure comply with the generally recognized international and European standards on the human rights protection of persons with mental disorder, and to identify the shortcomings of the existing mechanism of involuntary hospitalization. Taking into consideration the results of this analysis, the author points to the necessity of reforming the involuntary hospitalization procedure and proposes possible directions for a further improvement of this legal institute.

  3. Protective Effect of the Ethyl Acetate Fraction of Sargassum muticum against Ultraviolet B–Irradiated Damage in Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Jin Won Hyun

    2011-11-01

    Full Text Available The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME against ultraviolet B (UVB-induced cell damage in human keratinocytes (HaCaT cells. SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H2O2 and UVB-induced intracellular reactive oxygen species (ROS. SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4 + H2O2, which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis.

  4. Human rights and proactive displacement: determining the appropriate balance between the duty to protect and the right to remain.

    Science.gov (United States)

    McDermott, Ronan; Gibbons, Pat

    2017-07-01

    The proactive displacement by public authorities of populations from areas perceived to be exposed to a high risk of disaster presents complex human rights challenges. Provided that no ulterior motive is at play, the use of compulsory evacuations and relocations as policy responses to such risk is mandated by the duty to protect the right to life. However, proactive displacement in the interest of saving lives can be problematic as such measures can lead to the limitation of other human rights, resulting in an intricate assessment of whether compulsory evacuation or permanent relocation is proportional in any given circumstance. Such an analysis demands critical attention by public authorities to the perception of the disaster risk in question and problematises claims to objectivity of official risk assessments. Furthermore, it poses the question as to whether measures designed to address the disaster risk in question that are less intrusive than relocation may be available to public authorities. © 2017 The Author(s). Disasters © Overseas Development Institute, 2017.

  5. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

    Directory of Open Access Journals (Sweden)

    Didik Priyandoko

    Full Text Available The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera leaf extract on methoxyacetic acid (MAA induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  6. Protective effect of sodium selenite against the genotoxicity of aflatoxin B1 in human whole blood cultures

    Directory of Open Access Journals (Sweden)

    Fatime Geyikoglu

    2006-05-01

    Full Text Available This study was designed to investigate the effects of selenium and aflatoxin on human whole blood cultures (WBC in relation to induction of sister-chromatid exchange (SCE. The results showed that the frequency of SCEs in peripheral lymphocytes was significantly increased by the direct-acting mutagen AFB1 (at doses 5 and 10 µM except for 1µM compared to controls. When sodium selenite (Na2SeO3 was added alone at a molar ratio of 5x10-7 and 1x10-6, cells did not show significant increase in SCE frequency. Whereas, SCE rates induced by the various AFB1 concentrations could be significantly reduced by the presence of Na2SeO3 in a clear dose-related manner. These results indicated that selenite and AFB1 mutually antagonized their ability to cause DNA damage leading to the formation of SCEs. However, selenium didn't completely inhibit induction of SCEs by AFB1 compared to controls. This is first report describing, the protective ability of selenium againist AFB1 genotoxicity on human WBC.

  7. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

    Science.gov (United States)

    Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

    2011-05-04

    The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  8. Jatropha curcas leaf and bark fractions protect against ultraviolet radiation-B induced DNA damage in human peripheral blood lymphocytes.

    Science.gov (United States)

    Sundari, J; Selvaraj, R; Rajendra Prasad, N; Elumalai, R

    2013-11-01

    The present study is conducted to investigate the antioxidant potential of Jatropha curcas root bark extract (RB4 fraction) and leaf extract (L1 fraction), and to study their effects on UVB-radiation-induced DNA damage in cultured human blood lymphocytes. In this study, J. curcas showed strong antioxidant property in different free radical scavenging systems. Both the fractions effectively scavenged hydroxyl (OH), superoxide anion (O₂(·-)), 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(·+)) in a concentration-dependent manner. The IC₅₀ (Inhibitory Concentration 50) values of J. curcas fractions were compared to standard ascorbic acid used in this study. The antioxidant potential of a compound was directly proportional to the photoprotective effect. In this study, human peripheral blood lymphocytes (HPBL) were exposed to UVB-radiation and there was an increase in comet attributes (% tail DNA, tail length, tail movement and Olive tail moment). Jatropha curcas RB4 fraction and L1 fraction treatment before UVB-irradiation significantly decreased the % tail DNA, tail length, tail moment and Olive tail moment in irradiated HPBL. These results suggested that J. curcas exhibited strong antioxidant property and RB4 and L1 fractions protected UVB-radiation-induced DNA damage in HPBL. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. A kinematic model to estimate the effective dose of radioactive isotopes in the human body for radiological protection

    Science.gov (United States)

    Sasaki, S.; Yamada, T.

    2013-12-01

    The great earthquake attacked the north-east area in Japan in March 11, 2011. The system of electrical facilities to control Fukushima Daiichi nuclear power station was completely destroyed by the following tsunamis. From the damaged reactor containment vessels, an amount of radioactive substances had leaked and been diffused in the vicinity of this station. Radiological internal exposure becomes a serious social issue both in Japan and all over the world. The present study provides an easily understandable, kinematic-based model to estimate the effective dose of radioactive substances in a human body by simplified the complicated mechanism of metabolism. International Commission on Radiological Protection (ICRP) has developed an exact model, which is well-known as a standard method to calculate the effective dose for radiological protection. However, owing to that the above method accord too much with the actual mechanism of metabolism in human bodies, it becomes rather difficult for non-professional people of radiology to gasp the whole images of the movement and the influences of radioactive substances in a human body. Therefore, in the present paper we propose a newly-derived and easily-understandable model to estimate the effective dose. The present method is very similar with the traditional and conventional hydrological tank model. Ingestion flux of radioactive substances corresponds to rain intensity and the storage of radioactive substances to the water storage in a basin in runoff analysis. The key of this method is to estimate the energy radiated from the radioactive nuclear disintegration of an atom by using classical theory of E. Fermi of beta decay and special relativity for various kinds of radioactive atoms. The parameters used in this study are only physical half-time and biological half-time, and there are no intentional and operational parameters of coefficients to adjust our theoretical runoff to observation of ICRP. Figure.1 compares time

  10. DNA polymerase kappa protects human cells against MMC-induced genotoxicity through error-free translesion DNA synthesis.

    Science.gov (United States)

    Kanemaru, Yuki; Suzuki, Tetsuya; Sassa, Akira; Matsumoto, Kyomu; Adachi, Noritaka; Honma, Masamitsu; Numazawa, Satoshi; Nohmi, Takehiko

    2017-01-01

    Interactions between genes and environment are critical factors for causing cancer in humans. The genotoxicity of environmental chemicals can be enhanced via the modulation of susceptible genes in host human cells. DNA polymerase kappa (Pol κ) is a specialized DNA polymerase that plays an important role in DNA damage tolerance through translesion DNA synthesis. To better understand the protective roles of Pol κ, we previously engineered two human cell lines either deficient in expression of Pol κ (KO) or expressing catalytically dead Pol κ (CD) in Nalm-6-MSH+ cells and examined cytotoxic sensitivity against various genotoxins. In this study, we set up several genotoxicity assays with cell lines possessing altered Pol κ activities and investigated the protective roles of Pol κ in terms of genotoxicity induced by mitomycin C (MMC), a therapeutic agent that induces bulky DNA adducts and crosslinks in DNA. We introduced a frameshift mutation in one allele of the thymidine kinase (TK) gene of the KO, CD, and wild-type Pol κ cells (WT), thereby establishing cell lines for the TK gene mutation assay, namely TK+/- cells. In addition, we formulated experimental conditions to conduct chromosome aberration (CA) and sister chromatid exchange (SCE) assays with cells. By using the WT TK+/- and KO TK+/- cells, we assayed genotoxicity of MMC. In the TK gene mutation assay, the cytotoxic and mutagenic sensitivities of KO TK+/- cells were higher than those of WT TK+/- cells. MMC induced loss of heterozygosity (LOH), base pair substitutions at CpG sites and tandem mutations at GpG sites in both cell lines. However, the frequencies of LOH and base substitutions at CpG sites were significantly higher in KO TK+/- cells than in WT TK+/- cells. MMC also induced CA and SCE in both cell lines. The KO TK+/- cells displayed higher sensitivity than that displayed by WT TK+/- cells in the SCE assay. These results suggest that Pol κ is a modulating factor for the genotoxicity of MMC and

  11. Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations.

    Science.gov (United States)

    Sharpe, S; White, A; Sarfas, C; Sibley, L; Gleeson, F; McIntyre, A; Basaraba, R; Clark, S; Hall, G; Rayner, E; Williams, A; Marsh, P D; Dennis, M

    2016-12-01

    Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  12. Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve.

    Directory of Open Access Journals (Sweden)

    Leila Satarian

    Full Text Available BACKGROUND: Degeneration of retinal ganglion cells (RGCs is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs following intravitreal transplantation. METHODOLOGY/PRINCIPAL FINDINGS: NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs and transplanted into rats whose optic nerves have been crushed (ONC. hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM. The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers. CONCLUSIONS/SIGNIFICANCE: The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.

  13. (-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

    Science.gov (United States)

    Xie, Jianhui; Lin, Zhixiu; Xian, Yanfang; Kong, Songzhi; Lai, Zhengquan; Ip, Siupo; Chen, Haiming; Guo, Huizhen; Su, Zuqing; Yang, Xiaobo; Xu, Yang; Su, Ziren

    2016-06-01

    (-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions. Copyright © 2016. Published by Elsevier B.V.

  14. TLQP-21 protects human umbilical vein endothelial cells against high-glucose-induced apoptosis by increasing G6PD expression.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556-576. Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs, we demonstrated that TLQP-21 (10 or 50 nM dose-dependently prevented apoptosis under high-glucose (30 mmol/L conditions (the normal glucose concentration is 5.6 mmol/L. TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH and a reduction in the levels of reactive oxygen species (ROS. TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD, which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.

  15. Embryonic catalase protects against ethanol embryopathies in acatalasemic mice and transgenic human catalase-expressing mice in embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Miller-Pinsler, Lutfiya [Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Wells, Peter G., E-mail: pg.wells@utoronto.ca [Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario (Canada); Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada)

    2015-09-15

    Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol (EtOH) teratogenicity, but the protective role of the embryonic antioxidative enzyme catalase is unclear, as embryonic activity is only about 5% of maternal levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) controls, and C3Ga.Cg-Cat{sup b}/J catalase-deficient, acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on gestational day (GD) 9 (plug = GD 1), exposed for 24 h to 2 or 4 mg/mL EtOH or vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites developed, turning and head length, whereas hCat embryos were protected (p < 0.001). Maternal pretreatment of C57BL/6 WT dams with 50 kU/kg PEG-catalase (PEG-cat) 8 h prior to embryo culture, which increases embryonic catalase activity, blocked all EtOH embryopathies (p < 0.001). Vehicle-exposed aCat mouse embryos had lower yolk sac diameters compared to WT controls, suggesting that endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than WT controls, evidenced by reduced head length and somite development (p < 0.01), and trends for reduced anterior neuropore closure, turning and crown–rump length. Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies (p < 0.05). These data suggest that embryonic catalase is a determinant of risk for EtOH embryopathies. - Highlights: • Ethanol (EtOH) exposure causes structural embryopathies in embryo culture. • Genetically enhanced catalase (hCat) protects against EtOH embryopathies. • Genetically deficient catalase (aCat) exacerbates EtOH embryopathies. • Embryonic catalase is developmentally important. • Et

  16. Wounding patterns and human performance in knife attacks: optimising the protection provided by knife-resistant body armour.

    Science.gov (United States)

    Bleetman, A; Watson, C H; Horsfall, I; Champion, S M

    2003-12-01

    Stab attacks generate high loads, and to defeat them, armour needs to be of a certain thickness and stiffness. Slash attacks produce much lower loads and armour designed to defeat them can be far lighter and more flexible. Phase 1: Human performance in slash attacks: 87 randomly selected students at the Royal Military College of Science were asked to make one slash attack with an instrumented blade on a vertically mounted target. No instructions on how to slash the target were given. The direction, contact forces and velocity of each attack were recorded. Phase 2: Clinical experience with edged weapon attacks: The location and severity of all penetrating injuries in patients attending the Glasgow Royal Infirmary between 1993 and 1996 were charted on anatomical figures. Phase 1: Two types of human slash behaviour were evident: a 'chop and drag' blow and a 'sweep motion' type of attack. 'Chop and drag' attacks had higher peak forces and velocities than sweep attacks. Shoulder to waist blows (diagonal) accounted for 82% of attacks, 71% of attackers used a long diagonal slash with an average cut length of 34 cm and 11% used short diagonal attacks with an average cut length of 25 cm. Only 18% of attackers slashed across the body (short horizontal); the average measured cut length of this type was 28 cm. The maximum peak force for the total sample population was 212 N; the maximum velocity was 14.88 m s(-1). The 95 percentile force for the total sample population was 181 N and the velocity was 9.89 m s(-1). Phase 2: 431 of the 500 patients had been wounded with edged weapons. The average number of wounds sustained by victims in knife assaults was 2.4. The distribution of wounds by frequency and severity are presented. Anti-slash protection is required for the arms, neck, shoulders, and thighs. The clinical experience of knife-attack victims provides information on the relative vulnerabilities of different regions of the body. It is anticipated that designing a tunic

  17. Protection against oxidative damage in human erythrocytes and preliminary photosafety assessment of Punica granatum seed oil nanoemulsions entrapping polyphenol-rich ethyl acetate fraction

    OpenAIRE

    Baccarin,Thaisa; Mitjans, Montserrat; Lemos-Senna,Elenara; Vinardell, Maria Pilar

    2015-01-01

    The main purpose of the present study is to evaluate the ability of nanoemulsion entrapping pomegranate peel polyphenol-rich ethyl acetate fraction (EAF) prepared from pomegranate seed oil and medium chain triglyceride to protect human erythrocyte membrane from oxidative damage and to assess preliminary in vitro photosafety. In order to evaluate the phototoxic effect of nanoemulsions, human red blood cells (RBCs) are used as a biological model and the rate of haemolysis and photohaemolysis (5...

  18. PROTECTING HUMAN HEALTH AND THE ENVIRONMENT ON SIOUX TRIBAL LANDS: A PARTNERSHIP OF EPA AND TRIBAL EPD

    Science.gov (United States)

    Through environmental sampling performed by EPA and Cheyenne River Sioux Tribe Environmental Protection Division personnel, mercury contamination in managed pond systems in South Dakota was characterized and risk reduction recommendations were made to protect subsistence fisherma...

  19. Passive protection of mice against Streptococcus pneumoniae challenge by naturally occurring and vaccine-induced human anti-PhtD antibodies.

    Science.gov (United States)

    Brookes, Roger H; Ming, Marin; Williams, Kimberley; Hopfer, Robert; Gurunathan, Sanjay; Gallichan, Scott; Tang, Mei; Ochs, Martina M

    2015-01-01

    Currently marketed Streptococcus pneumoniae vaccines are based on polysaccharide capsular antigens from the most common strains. Pneumococcal histidine triad protein D (PhtD) is a conserved surface protein that is being evaluated as a candidate for a vaccine with improved serotype coverage. Here, we measured the functional activity of human anti-PhtD antibodies in a passive protection model wherein mice were challenged with a lethal dose of S. pneumoniae by intravenous injection. This functional activity was compared with anti-PhtD antibody concentrations measured by enzyme-linked immunosorbent assay (ELISA) to estimate the 50% protective dose (ED50). Anti-PhtD antibodies affinity purified from pooled normal human sera passively protected mice with an ED50 of 1679 ELISA units/ml (95% confidence interval, 1420-1946). Sera from subjects injected with aluminum-adjuvanted PhtD in a phase I trial had similar activity per unit of antibody (ED50 = 1331 ELISA units/ml [95% confidence interval, 762-2038]). Vaccine-induced activity in the passive protection model was blocked by pre-incubation with recombinant PhtD but not by a control S. pneumoniae antigen (LytB). These results show that human anti-PhtD antibodies, whether naturally acquired or induced by the PhtD candidate vaccine, are functional. This supports the development of the PhtD candidate as part of a broadly protective pneumococcal vaccine.

  20. Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.

    Directory of Open Access Journals (Sweden)

    Zhihui Chen

    2011-04-01

    Full Text Available HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2. CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc, and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.

  1. Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals.

    Science.gov (United States)

    Narmada, Balakrishnan Chakrapani; Goh, Yeek Teck; Li, Huan; Sinha, Sanjay; Yu, Hanry; Cheung, Christine

    2017-03-01

    Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851-863. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  2. Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated β-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved

    DEFF Research Database (Denmark)

    Rondas, Dieter; Bugliani, Marco; D’Hertog, Wannes

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles...... of human islets of Langerhans treated with cytokines (IL-1β and IFN-γ) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated β-cell protection. Co-incubation of cytokine......-treated human islets with GLP-1 resulted in a marked protection of β-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression...

  3. Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada

    OpenAIRE

    Kohli Michele; Lawrence Donna; Haig Jennifer; Anonychuk Andrea; Demarteau Nadia

    2012-01-01

    Background In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV) types −16 and −18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW) while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting. Methods A Markov model of the natural history of ...

  4. Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16.

    Science.gov (United States)

    Ghaemi, Amir; Soleimanjahi, Hoorieh; Gill, Pooria; Hassan, Zuhair M; Razeghi, Soodeh; Fazeli, Maryam; Razavinikoo, Seyed Mohammad H

    2011-01-01

    Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 10(12) particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia. Copyright © 2010 S. Karger AG, Basel.

  5. Human milk feeding protects very low-birth-weight infants from retinopathy of prematurity: a pre-post cohort analysis.

    Science.gov (United States)

    Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

    2016-12-01

    To examine the effect of early human milk (HM) feeding on the incidence of retinopathy of prematurity (ROP) among very low-birth-weight (VLBW) infants. Observational cohort research in a Level III neonatal intensive care unit. A total of 186 infants were enrolled in this pre-post cohort study (114 infants were included in the HM-fed group and 72 in the formula-fed group). ROP, type of feeding (early exclusive HM versus any formula), and potential confounding variables were measured. Differences between groups were explored. The clinical characteristics of the neonates did not differ between the two groups. By bivariate analysis, HM feeding was associated with 75% lower odds of Stage 2 or 3 ROP (OR = 0.25, 95% CI: 0.091 to 0.705; p = 0.009) At multivariate logistic regression, type of milk feeding retained significance, exclusive HM being protective with p = 0.002. This study found an association between early exposure to formula in VLBW infants and ROP. An initial HM diet, devoid of cow milk-containing products before achieving full enteral feeding, may help prevent ROP.

  6. Tanshinone II-A is protective against human umbilical vein endothelial cell injury after exposure to serum from preeclampsia patients.

    Science.gov (United States)

    Wu, ChunFeng; Yuan, Jing; Sui, RenFang; Li, ShuYuan; Sun, JingXia

    2014-01-01

    Preeclampsia (PE) is one of the most common and dangerous complications during pregnancy and is characterized by high blood pressure and significant amounts of protein in the urine. Vascular endothelial cell dysfunction is the major pathology in PE. This study was designed to assay the effects of tanshinone II-A (TII-A) on human umbilical vein endothelial cell (HUVEC) injury after incubation with serum from PE patients and to determine the underlying mechanism. After treating HUVECs with different TII-A concentrations, cell viability, apoptosis and CD40/CD40 ligand (CD40L) mRNA and protein expression levels were measured. Incubation of HUVECs with serum from PE patients induced morphological alterations, caused decreased cell viability and increased the rate of apoptosis. However, TII-A (5-40 μg/ml) significantly reversed these injuries. Importantly, preapplication of TII-A attenuated PE sera-induced expression of CD40 and CD40L mRNA and protein. TII-A has a protective effect against PE sera, likely through regulation of the CD40/CD40L signal transduction pathway. © 2014 S. Karger AG, Basel.

  7. Polyphenol-Rich Strawberry Extract Protects Human Dermal Fibroblasts against Hydrogen Peroxide Oxidative Damage and Improves Mitochondrial Functionality

    Directory of Open Access Journals (Sweden)

    Francesca Giampieri

    2014-06-01

    Full Text Available Strawberry bioactive compounds are widely known to be powerful antioxidants. In this study, the antioxidant and anti-aging activities of a polyphenol-rich strawberry extract were evaluated using human dermal fibroblasts exposed to H2O2. Firstly, the phenol and flavonoid contents of strawberry extract were studied, as well as the antioxidant capacity. HPLC-DAD analysis was performed to determine the vitamin C and β-carotene concentration, while HPLC-DAD/ESI-MS analysis was used for anthocyanin identification. Strawberry extract presented a high antioxidant capacity, and a relevant concentration of vitamins and phenolics. Pelargonidin- and cyanidin-glycosides were the most representative anthocyanin components of the fruits. Fibroblasts incubated with strawberry extract and stressed with H2O2 showed an increase in cell viability, a smaller intracellular amount of ROS, and a reduction of membrane lipid peroxidation and DNA damage. Strawberry extract was also able to improve mitochondrial functionality, increasing the basal respiration of mitochondria and to promote a regenerative capacity of cells after exposure to pro-oxidant stimuli. These findings confirm that strawberries possess antioxidant properties and provide new insights into the beneficial role of strawberry bioactive compounds on protecting skin from oxidative stress and aging.

  8. Protective Effects of a New Phloretin Derivative against UVB-Induced Damage in Skin Cell Model and Human Volunteers

    Directory of Open Access Journals (Sweden)

    Seoungwoo Shin

    2014-10-01

    Full Text Available The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS, a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs formation, glutathione (GSH depletion and apoptosis induced by ultraviolet B (UVB. The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection.

  9. The protective effects of silybin on the cytotoxicity of thiram in human, rat and chicken cell cultures.

    Science.gov (United States)

    Radko, Lidia; Cybulski, Wojciech; Rzeski, Wojciech

    2017-11-01

    The study objective was a determination of thiram cytotoxicity and silybin cytoprotective activity in course of the fungicide impact on cell metabolism and membrane integrity. Firstly, human, rat, chicken hepatoma cells and rat myoblasts cultures were incubated with thiram. The results showed higher sensitivity of myoblasts on thiram exposure than the hepatoma cells. Among hepatoma cells, the chicken cultures were the most sensitive on the fungicide endangering. The mitochondrial activity was the most thiram affected function within all types the cell lines used. When silybin co-acted with thiram, an increase of the cell viability was recorded. The EC50-values were higher for thiram subjected to interaction with silybin than the effect of alone thiram action. The interaction mode between the studied compounds shown by combination index (CI) represented an antagonistic or an additive nature and was depended on thiram concentration, type of the cells and the assay used. Moreover, the morphology changes were dependent on silybin presence in the cell cultures subjected to thiram impact at the same time. Staining with Hoechst 33342 and propidium ioidium revealed the apoptosis cell death in the incubation cultures. Definitely, the results have shown a potential of silybin to protect the cultured cells in course of cytotoxicity induced by thiram. However, future studies taking into account other endpoints of thiram cytotoxicity pathways including species differences and the cytoprotection efficacy could be of interest. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional nonlinear feedback.

    Science.gov (United States)

    Wilson, K; Auer, M; Binnie, M; Zheng, X; Pham, N T; Iredale, J P; Webster, S P; Mole, D J

    2016-04-14

    Kynurenine 3-monooxygenase (KMO) is a critical regulator of inflammation. The preferred KMO substrate, kynurenine, is converted to 3-hydroxykynurenine (3HK), and this product exhibits cytotoxicity through mechanisms that culminate in apoptosis. Here, we report that overexpression of human KMO with orthotopic localisation to mitochondria creates a metabolic environment during which the cell exhibits increased tolerance for exogenous 3HK-mediated cellular injury. Using the selective KMO inhibitor Ro61-8048, we show that KMO enzyme function is essential for cellular protection. Pan-caspase inhibition with Z-VAD-FMK confirmed apoptosis as the mode of cell death. By defining expression of pathway components upstream and downstream of KMO, we observed alterations in other key kynurenine pathway components, particularly tryptophan-2,3-dioxygenase upregulation, through bidirectional nonlinear feedback. KMO overexpression also increased expression of inducible nitric oxide synthase (iNOS). These changes in gene expression are functionally relevant, because siRNA knockdown of the pathway components kynureninase and quinolinate phosphoribosyl transferase caused cells to revert to a state of susceptibility to 3HK-mediated apoptosis. In summary, KMO overexpression, and importantly KMO activity, have metabolic repercussions that fundamentally affect resistance to cell stress.

  11. Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara.

    Science.gov (United States)

    Webster, Daniel P; Dunachie, Susanna; Vuola, Jenni M; Berthoud, Tamara; Keating, Sheila; Laidlaw, Stephen M; McConkey, Samuel J; Poulton, Ian; Andrews, Laura; Andersen, Rikke F; Bejon, Philip; Butcher, Geoff; Sinden, Robert; Skinner, Michael A; Gilbert, Sarah C; Hill, Adrian V S

    2005-03-29

    Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria.

  12. Overexpression of Telomerase Protects Human and Murine Lung Epithelial Cells from Fas- and Bleomycin-Induced Apoptosis via FLIP Upregulation.

    Directory of Open Access Journals (Sweden)

    Nissim Arish

    be a novel mechanism to confer protection from apoptosis in bleomycin-exposed human lung epithelial cells.

  13. AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates.

    Science.gov (United States)

    Jeyanathan, Mangalakumari; Shao, Zhongqi; Yu, Xuefeng; Harkness, Robin; Jiang, Rong; Li, Junqiang; Xing, Zhou; Zhu, Tao

    2015-01-01

    Persisting high global tuberculosis (TB) morbidity and mortality and poor efficacy of BCG vaccine emphasizes an urgent need for developing effective novel boost vaccination strategies following parenteral BCG priming in humans. Most of the current lead TB vaccine candidates in the global pipeline were developed for parenteral route of immunization. Compelling evidence indicates respiratory mucosal delivery of vaccine to be the most effective way to induce robust local mucosal protective immunity against pulmonary TB. However, despite ample supporting evidence from various animal models, there has been a lack of evidence supporting the safety and protective efficacy of respiratory mucosal TB vaccination in non-human primates (NHP) and humans. By using a rhesus macaque TB model we have evaluated the safety and protective efficacy of a recombinant human serotype 5 adenovirus-based TB vaccine (AdHu5Ag85A) delivered via the respiratory mucosal route. We show that mucosal AdHu5Ag85A boost immunization was safe and well tolerated in parenteral BCG-primed rhesus macaques. A single AdHu5Ag85A mucosal boost immunization in BCG-primed rhesus macaques enhanced the antigen-specific T cell responses. Boost immunization significantly improved the survival and bacterial control following M.tb challenge. Furthermore, TB-related lung pathology and clinical outcomes were lessened in BCG-primed, mucosally boosted animals compared to control animals. Thus, for the first time we show that a single respiratory mucosal boost immunization with a novel TB vaccine enhances protection against pulmonary TB in parenteral BCG-primed NHP. Our study provides the evidence for the protective potential of AdHu5Ag85A as a respiratory mucosal boost TB vaccine for human application.

  14. Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans

    Science.gov (United States)

    Jafari, Samah; Prince, Rebecca A; Kim, Daniel Y; Paydarfar, David

    2003-01-01

    During swallowing, the airway is protected from aspiration of ingested material by brief closure of the larynx and cessation of breathing. Mechanoreceptors innervated by the internal branch of the superior laryngeal nerve (ISLN) are activated by swallowing, and connect to central neurones that generate swallowing, laryngeal closure and respiratory rhythm. This study was designed to evaluate the hypothesis that the ISLN afferent signal is necessary for normal deglutition and airway protection in humans. In 21 healthy adults, we recorded submental electromyograms, videofluoroscopic images of the upper airway, oronasal airflow and respiratory inductance plethysmography. In six subjects we also recorded pressures in the hypopharynx and upper oesophagus. We analysed swallows that followed a brief infusion (4–5 ml) of liquid barium onto the tongue, or a sip (1–18 ml) from a cup. In 16 subjects, the ISLN was anaesthetised by transcutaneous injection of bupivacaine into the paraglottic compartment. Saline injections using the identical procedure were performed in six subjects. Endoscopy was used to evaluate upper airway anatomy, to confirm ISLN anaesthesia, and to visualise vocal cord movement and laryngeal closure. Comparisons of swallowing and breathing were made within subjects (anaesthetic or saline injection vs. control, i.e. no injection) and between subjects (anaesthetic injection vs. saline injection). In the non-anaesthetised condition (saline injection, 174 swallows in six subjects; no injection, 522 swallows in 20 subjects), laryngeal penetration during swallowing was rare (1.4 %) and tracheal aspiration was never observed. During ISLN anaesthesia (16 subjects, 396 swallows), all subjects experienced effortful swallowing and an illusory globus sensation in the throat, and 15 subjects exhibited penetration of fluid into the larynx during swallowing. The incidence of laryngeal penetration in the anaesthetised condition was 43 % (P deglutition, especially for

  15. Noise Protection

    Science.gov (United States)

    1980-01-01

    Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

  16. A Conflict Transformation Perspective on Efforts to Protect Human Rights of Haitian Migrants and their Descendants in the Dominican Republic

    Directory of Open Access Journals (Sweden)

    Ingvild Skeie

    2016-04-01

    Full Text Available Este artículo trata el largo debate en los ámbitos académico y profesional, sobre la relación entre la protección de los derechos humanos y la transformación de conflictos. Son dos enfoques que frecuentemente se han presentado como dos opuestos, representando respectivamente los principios y el pragmatismo. Sin embargo, durante los últimos años, se ha notado una tendencia de considerar cómo ambos campos pueden beneficiarse de las herramientas y las ideas del otro. El artículo utiliza la situación de la República Dominicana como un estudio de caso, observando los esfuerzos de la sociedad civil para promover y proteger los derechos de inmigrantes haitianos y sus descendientes, enfocándose particularmente en el papel de las organizaciones no gubernamentales internacionales (‘INGOs’, por sus siglas en inglés. El artículo argumenta la utilidad de la aplicación del análisis de transformación de conflicto, y específicamente intenta mostrar la relevancia de usar un análisis sistémico de conflicto, analizando y entendiendo los abusos contra los derechos humanos dentro de en una perspectiva más amplia de las relaciones dominico-haitianas. El artículo muestra cómo las intervenciones de las INGO afecta las dinámicas del conflicto tanto positivamente como negativamente, y discute las implicaciones para futuras estrategias para los participantes de la sociedad civil. English: This paper addresses the long-standing debate within academic and practitioner circles about the relationship between human rights protection and conflict transformation. While the two approaches have often been pitted against each other, as representing principles vs. pragmatism respectively, there has over the last years been an increasing tendency to consider how the two camps can benefit from each other's tools and lines of thoughts. The article takes the situation in the Dominican Republic as a case, looking into civil society actors' efforts to promote

  17. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

    Science.gov (United States)

    Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

    2012-01-01

    The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

  18. Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

    Science.gov (United States)

    Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

    2017-03-01

    Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and

  19. Systematic and intestinal antibody-secreting cell responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.

    Science.gov (United States)

    Yuan, L; Ward, L A; Rosen, B I; To, T L; Saif, L J

    1996-05-01

    Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal-suspension) Wa strain human rotavirus (which mimics human natural infection) developed diarrhea, and most pigs which recovered (87% protection rate) were immune to disease upon homologous virulent virus challenge at postinoculation day (PID) 21. Pigs inoculated with cell culture-attenuated Wa rotavirus (which mimics live oral vaccines) developed subclinical infections and seroconverted but were only partially protected against challenge (33% protection rate). Isotype-specific antibody-secreting cells (ASC were enumerated at selected PID in intestinal (duodenal and ileal lamina propria and mesenteric lymph node [MLN]) and systemic (spleen and blood) lymphoid tissues by using enzyme-linked immunospot assays. At challenge (PID 21), the numbers of virus-specific immunoglobulin A (IgA) ASC, but not IgG ASC, in intestines and blood were significantly greater in virulent-Wa rotavirus-inoculated pigs than in attenuated-Wa rotavirus-inoculated pigs and were correlated (correlation coefficients: for duodenum and ileum, 0.9; for MLN, 0.8; for blood, 0.6) with the degree of protection induced. After challenge, the numbers of IgA and IgG virus-specific ASC and serum-neutralizing antibodies increased significantly in the attenuated-Wa rotavirus-inoculated pigs but not in the virulent-Wa rotavirus-inoculated pigs (except in the spleen and except for IgA ASC in the duodenum). The transient appearance of IgA ASC in the blood mirrored the IgA ASC responses in the gut, albeit at a lower level, suggesting that IgA ASC in the blood of humans could serve as an indicator for IgA ASC responses in the intestine after rotavirus infection. To our knowledge, this is the first report to study and identify intestinal IgA ASC as a correlate of protective active immunity in an animal model of human-rotavirus-induced disease.

  20. Dual Heat Pulse, Dual Layer Thermal Protection System Sizing Analysis and Trade Studies for Human Mars Entry Descent and Landing

    Science.gov (United States)

    McGuire, Mary Kathleen

    2011-01-01

    NASA has been recently updating design reference missions for the human exploration of Mars and evaluating the technology investments required to do so. The first of these started in January 2007 and developed the Mars Design Reference Architecture 5.0 (DRA5). As part of DRA5, Thermal Protection System (TPS) sizing analysis was performed on a mid L/D rigid aeroshell undergoing a dual heat pulse (aerocapture and atmospheric entry) trajectory. The DRA5 TPS subteam determined that using traditional monolithic ablator systems would be mass expensive. They proposed a new dual-layer TPS concept utilizing an ablator atop a low thermal conductivity insulative substrate to address the issue. Using existing thermal response models for an ablator and insulative tile, preliminary hand analysis of the dual layer concept at a few key heating points indicated that the concept showed potential to reduce TPS masses and warranted further study. In FY09, the followon Entry, Descent and Landing Systems Analysis (EDL-SA) project continued by focusing on Exploration-class cargo or crewed missions requiring 10 to 50 metric tons of landed payload. The TPS subteam advanced the preliminary dual-layer TPS analysis by developing a new process and updated TPS sizing code to rapidly evaluate mass-optimized, full body sizing for a dual layer TPS that is capable of dual heat pulse performance. This paper describes the process and presents the results of the EDL-SA FY09 dual-layer TPS analyses on the rigid mid L/D aeroshell. Additionally, several trade studies were conducted with the sizing code to evaluate the impact of various design factors, assumptions and margins.

  1. Evaluation of a laser equipped rifle for the US Army Human Engineering Laboratory, Aberdeen Proving Ground, Maryland, January 1977. Nonionizing radiation protection special study

    Energy Technology Data Exchange (ETDEWEB)

    Lyon, T.L.; Del Valle, P.F.

    1977-01-01

    A special study of the optical radiation hazards associated with the operation of a He-Ne laser mounted to an American International Corporation Model 180 Law Enforcement Rifle was performed by this Agency. Radiometric measurements were conducted on 11 January 1977, for the US Army Human Engineering Laboratory at Aberdeen Proving Ground. It was determined that the protection standards for momentary viewing were exceeded out to a hazard distance of 9 m and to 100 m when viewing through an optical instrument. Long-term staring at the laser from within the beam exceeded the protection standards out to a caution distance of 490 m. (Author)

  2. The right choice of antihypertensives protects primary human hepatocytes from ethanol- and recombinant human TGF-β1-induced cellular damage

    Directory of Open Access Journals (Sweden)

    Ehnert S

    2013-03-01

    damage, except for furosemide, which had no effect. As a common mechanism, all antihypertensives increased heme-oxygenase-1 (HO-1 expression, and inhibition of HO-1 activity reversed the protective effect of the drugs. Interestingly, Smad3/4 signaling was reduced by all compounds except furosemide, which even enhanced this profibrotic signaling. This effect was mediated by expressional changes of Smad3 and/or Smad4.Conclusions: Our results suggest that antihypertensives may both positively and negatively influence chronic liver disease progression. Therefore, we propose that in future patients with ALD and high blood pressure, they could benefit from an adjusted antihypertensive therapy with additional antifibrotic effects.Keywords: primary human hepatocytes, alcoholic liver disease, ethanol, TGF-β1, antihypertensives

  3. The right choice of antihypertensives protects primary human hepatocytes from ethanol- and recombinant human TGF-β1-induced cellular damage.

    Science.gov (United States)

    Ehnert, Sabrina; Lukoschek, Teresa; Bachmann, Anastasia; Martínez Sánchez, Juan J; Damm, Georg; Nussler, Natascha C; Pscherer, Stefan; Stöckle, Ulrich; Dooley, Steven; Mueller, Sebastian; Nussler, Andreas K

    2013-01-01

    Patients with alcoholic liver disease (ALD) often suffer from high blood pressure and rely on antihypertensive treatment. Certain antihypertensives may influence progression of chronic liver disease. Therefore, the aim of this study is to investigate the impact of the commonly used antihypertensives amlodipine, captopril, furosemide, metoprolol, propranolol, and spironolactone on alcohol-induced damage toward human hepatocytes (hHeps). hHeps were isolated by collagenase perfusion. Reactive oxygen species (ROS) were measured by fluorescence-based assays. Cellular damage was determined by lactate-dehydrogenase (LDH)-leakage. Expression analysis was performed by reverse-transcription polymerase chain reaction and Western blot. Transforming growth factor (TGF)-β signaling was investigated by a Smad3/4-responsive luciferase-reporter assay. Ethanol and TGF-β1 rapidly increased ROS in hHeps, causing a release of 40%-60% of total LDH after 72 hours. All antihypertensives dose dependently reduced ethanol-mediated oxidative stress and cellular damage. Similar results were observed for TGF-β1-dependent damage, except for furosemide, which had no effect. As a common mechanism, all antihypertensives increased heme-oxygenase-1 (HO-1) expression, and inhibition of HO-1 activity reversed the protective effect of the drugs. Interestingly, Smad3/4 signaling was reduced by all compounds except furosemide, which even enhanced this profibrotic signaling. This effect was mediated by expressional changes of Smad3 and/or Smad4. Our results suggest that antihypertensives may both positively and negatively influence chronic liver disease progression. Therefore, we propose that in future patients with ALD and high blood pressure, they could benefit from an adjusted antihypertensive therapy with additional antifibrotic effects.

  4. Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.

    Directory of Open Access Journals (Sweden)

    Melanie Kremer

    Full Text Available Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.

  5. Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.

    Science.gov (United States)

    Kremer, Melanie; Suezer, Yasemin; Volz, Asisa; Frenz, Theresa; Majzoub, Monir; Hanschmann, Kay-Martin; Lehmann, Michael H; Kalinke, Ulrich; Sutter, Gerd

    2012-01-01

    Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.

  6. Antioxidant Chemo-Protective Role Of Buffalo Colostrum And Milk Whey Derived Peptide Against 2 4-Dinitrophenol Induced-Oxidative Damage On Human Plasma In Vitro.

    Directory of Open Access Journals (Sweden)

    Alemayehu Letebo Albejo

    2017-09-01

    Full Text Available This study investigates the role of buffalo colostrum and milk whey derived peptides in protection against oxidative damage induced by 2 4-Dinitrophenol 2 4-DNP in human blood serum samples in vitro. A biomarker enzymes for oxidative stress like Alkaline phosphatase ALP and acid phosphatase ACP oxidative damage markers indicating extent of host antioxidant reserve indicators like reduced glutathione GSH were measured by spectrophotometric techniques in four different groups namely 1 Human blood plasma only control 2 Human blood plasma 24-DNP 3 Human blood plasma colostrum whey derived peptides 24-DNP 4 Human blood plasma colostrum whey derived peptides 5 Human blood plasma milk whey derived peptides 24-DNP and 6 Human blood plasma milk whey derived peptides. Following exposure to 2 4-DNP levels of antioxidants like GSH was significantly decreased in comparison to control e.g. GSH 0.568 0.015 vs0.871 0.022mol0.1 mg proteins. In addition the concentration of biomarker enzymes for 24-DNP induced membrane damage and oxidative stress like ALP and ACP were increased in serum by oxidant compared to control e.g. ALP 5.497 0.185 vs. 2.782 0.000molmg protein ACP 1.689 0.047 vs. 0.629 0.047molmg protein. Pretreatment with buffalo whey derived peptides significantly protects 24-DNP induced RBC membrane lyses and release of ALP and ACP into serum environment. e.g. ALP 3.444 0.094 vs. 5.497 0.185 molmg protein ACP 0.629 0.047 vs. 1.689 0.047molmg protein. Pretreatment with whey derived peptides give protection to oxidative damage and shifts the trend towards amelioration and replenishment of the antioxidant status.

  7. Polygonum multiflorum Radix extract protects human foreskin melanocytes from oxidative stress in vitro and potentiates hair follicle pigmentation ex vivo.

    Science.gov (United States)

    Sextius, P; Betts, R; Benkhalifa, I; Commo, S; Eilstein, J; Massironi, M; Wang, P; Michelet, J-F; Qiu, J; Tan, X; Jeulin, S

    2017-08-01

    To examine the ability of an extract from traditional Chinese medicine, Polygonum multiflorum Radix, to protect melanocyte viability from oxidative stress, a key mechanism in the initiation and progression of hair greying. To assess the antioxidant capacity of Polygonum multiflorum Radix extract, primary human foreskin melanocytes were treated with a commercially available Polygonum multiflorum Radix extract added to culture medium and exposed to hydrogen peroxide (H 2 O 2 ), using intracellular reactive oxygen species concentrations and glutathione/protein ratios as endpoints. To improve solubility for cosmetic uses, a new Polygonum multiflorum Radix extract was derived. As hair greying is the consequence of melanocyte disappearance in an oxidative stress environment, we checked whether the antioxidant capacity of the new Polygonum multiflorum Radix extract could preserve melanocyte viability in response to H 2 O 2 -induced oxidative stress, and preserve pigmentation within ex vivo human hair follicles. In vitro treatment of primary human foreskin melanocytes with traditional available Polygonum multiflorum Radix extract resulted in decreased intracellular ROS accumulation in response to H 2 O 2 exposure with a concomitant preservation of glutathione-to-protein ratio, consistent with a protective response against H 2 O 2 exposure and demonstrating the promise of this extract for protecting melanocytes against oxidative stress. Melanocytes treated with the improved Polygonum multiflorum Radix extract exhibited attenuated H 2 O 2 -induced cell death, demonstrating a clear cytoprotective effect. Treatment of ex vivo human hair follicles with the improved Polygonum multiflorum Radix extract resulted in a higher level of melanin compared to vehicle-treated controls, demonstrating an ex vivo protective effect on hair pigmentation. Polygonum multiflorum Radix extract protects in vitro primary human foreskin melanocytes from the deleterious effects of H 2 O 2

  8. The band III ligand dipyridamole protects human RBCs during photodynamic treatment while extracellular virus inactivation is not affected

    NARCIS (Netherlands)

    Besselink, G. A. J.; van Engelenburg, F. A. C.; Korsten, H. G.; Blokker, D. E.; Lagerberg, J. W. A.; Brand, A.; de Korte, D.; Verhoeven, A. J.

    2002-01-01

    BACKGROUND: Recently, the potential usefulness of dipyridamole (DIP) in protecting RBCs against the harmful side effects of photodynamic sterilization was demonstrated. In the present study, the use of DIP for selective protection of RBCs was investigated under conditions more relevant for blood

  9. Human Mesenchymal Stem Cells Provide Protection against Radiation-Induced Liver Injury by Antioxidative Process, Vasculature Protection, Hepatocyte Differentiation, and Trophic Effects

    Directory of Open Access Journals (Sweden)

    Sabine Francois

    2013-01-01

    Full Text Available To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1α. A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages.

  10. Synergy between sulforaphane and selenium in the up-regulation of thioredoxin reductase and protection against hydrogen peroxide-induced cell death in human hepatocytes.

    Science.gov (United States)

    Li, Dan; Wang, Wei; Shan, Yujuan; Barrera, Lawrence N; Howie, Alexander F; Beckett, Geoffrey J; Wu, Kun; Bao, Yongping

    2012-07-15

    Dietary isothiocyanates and selenium are chemopreventive agents and potent inducers of antioxidant enzymes. It has been previously shown that sulforaphane and selenium have a synergistic effect on the upregulation of thioredoxin reductase-1 (TrxR-1) in human hepatoma HepG2 cells. In this paper, further evidence is presented to show that sulforaphane and selenium synergistically induce TrxR-1 expression in immortalised human hepatocytes. Sulforaphane was found to be more toxic toward hepatocytes than HepG2 cells with IC50=25.1 and 56.4 μM, respectively. Sulforaphane can protect against hydrogen peroxide-induced cell death and this protection was enhanced by co-treatment with selenium. Using siRNA to knock down TrxR-1 or Nrf2, sulforaphane (5 μM)-protected cell viability was reduced from 73% to 46% and 34%, respectively, suggesting that TrxR-1 is an important enzyme in protection against hydrogen peroxide-induced cell death. Sulforaphane-induced TrxR-1 expression was positively associated with significant levels of Nrf2 translocation into the nucleus, but co-treatment with selenium showed no significant increase in Nrf2 translocation. Moreover, MAPK (ERK, JNK and p38) and PI3K/Akt signalling pathways were found to play no significant role in sulforaphane-induced Nrf2 translocation into the nucleus. However, blocking ERK and JNK signalling pathways decreased sulforaphane-induced TrxR-1 mRNA by about 20%; whereas blocking p38 and PI3K/AKT increased TrxR-1 transcription. In summary, a combination of sulforaphane and selenium resulted in a synergistic upregulation of TrxR-1 that contributed to the enhanced protection against free radical-mediated oxidative damage in human hepatocytes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are protective in a mouse passive transfer model.

    Directory of Open Access Journals (Sweden)

    M Keith Howard

    Full Text Available BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.

  12. Dynamics of Change in Human-Driven and Natural Systems: Fast Forward, Slow Motion, Same Movie? A Case Study from Plant Protection

    Directory of Open Access Journals (Sweden)

    Didier Andrivon

    2012-03-01

    Full Text Available Evolutionary biology and evolutionary ecology deal with change in species and ecosystems over time, and propose mechanisms to explain and predict these. In particular, they look for generic elements that will drive any organism or phylum to adaptive changes or to extinction. This paper, using examples from the field of plant protection against pests and diseases, shows that the patterns of change observed in natural and in human-driven systems are comparable, and proposes that their similarities result from the same mechanisms operating at different paces. Human-driven systems can thus be seen simply as ‘fast-forward’ versions of natural systems, making them tractable tools to test and predict elements from evolutionary theory. Conversely, the convergence between natural and human-driven systems opens opportunities for a more widespread use of evolutionary theory when analyzing and optimizing any human-driven system, or predicting its adaptability to changing conditions.

  13. Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein.

    Science.gov (United States)

    Schepens, Bert; Sedeyn, Koen; Vande Ginste, Liesbeth; De Baets, Sarah; Schotsaert, Michael; Roose, Kenny; Houspie, Lieselot; Van Ranst, Marc; Gilbert, Brian; van Rooijen, Nico; Fiers, Walter; Piedra, Pedro; Saelens, Xavier

    2014-11-01

    Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcγRI and FcγRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  14. A Prophylactic Multivalent Vaccine Against Different Filovirus Species is Immunogenic and Provides Protection from Lethal Infections of Ebolavirus and Marburgvirus Species in Non-Human Primates

    Science.gov (United States)

    2016-12-22

    1985;54(1): 30-37. Coltart CE, Johnson AM, Whitty CJ. Role of healthcare workers in early epidemic spread of Ebola: policy implications of...Lethal Infections of Ebolavirus and Marburgvirus Species in Non-human Primates Short title 70 characters Immunogenicity and Protection of a...filovirus species has been prompted by sporadic but large outbreaks of Ebolavirus and Marburgvirus infections . A good prophylactic vaccine should be able

  15. Compounds isolated from Eriobotrya deflexa leaves protect against ultraviolet radiation B-induced photoaging in human fibroblasts.

    Science.gov (United States)

    Huang, Chung-Yu; Lin, Yi-Tzu; Kuo, Hsiang-Chun; Chiou, Wen-Fei; Lee, Mei-Hsien

    2017-10-01

    Ultraviolet (UV) irradiation leads to skin photoaging because of the upregulation of matrix metalloproteinase (MMP)-1 and downregulation of type I collagen and tissue inhibitor of metalloproteinase (TIMP)-1. Eriobotrya deflexa (Hemsl.) Nakai (Rosaceae) is a flowering plant endemic to Taiwan, and its leaves have been used as an expectorant and in antitussive folk remedy. Our previous studies have demonstrated that an E. deflexa leaf extract functions as a free radical scavenger. The current evaluated the antiphotoaging effect of partitioned fractions and specific compounds from the leaves of E. deflexa by using bioguided isolation, compound identification, and biological activity testing with UVB-irradiated human fibroblasts (WS-1 cells). E. deflexa leaves were extracted with 95% ethanol and then partitioned using a sequential treatment of n-hexane, ethyl acetate, and n-butanol (n-BuOH). The bioactive n-BuOH fraction was used for isolation and purification through chromatography. The compounds were identified by analyzing their physical and spectroscopic properties. We identified eight compounds from this fraction; of these compounds, 3-O-α-l-rhamnopyranosyl-(1‴→6″)-β-d-galactopyranoside (1), hyperin (2), afzelin (5), and cryptochlorogenic acid methyl ester (7) were isolated from E. deflexa for the first time, and they exhibited MMP-1 inhibition activity. The IC50 values were 96.5, 89.5, 93.4, and 92.8μM for 1, 2, 5, and 7, respectively. These compounds also enhanced the expression of procollagen type I, and TIMP-1 and hyperin (2) were found to be most effective with IC50 values of 56.7 and 70.3μM, respectively. Hyperin (2) could reduce intracellular reactive oxygen species production in UVB-irradiated WS-1 cells, with the corresponding IC50 value being 80.7μM. Liquid chromatography triple-quadrupole mass spectrometry was used for the quantitative and chemical fingerprint analysis of active compounds. Quercetin 3-O-α-l-rhamnopyranosyl-(1‴→6

  16. Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans.

    Directory of Open Access Journals (Sweden)

    Matthew R Sandbulte

    2007-02-01

    Full Text Available BACKGROUND: A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA of H5N1 viruses (avN1 and of endemic human H1N1 viruses (huN1 are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection. METHODS AND FINDINGS: Mice were immunized against the NA of a contemporary human H1N1 strain by DNA vaccination. They were challenged with recombinant A/Puerto Rico/8/34 (PR8 viruses bearing huN1 (PR8-huN1 or avN1 (PR8-avN1 or with H5N1 virus A/Vietnam/1203/04. Additional naïve mice were injected with sera from vaccinated mice prior to H5N1 challenge. Also, serum specimens from humans were analyzed for reactivity with avN1. Immunization elicited a serum IgG response to huN1 and robust protection against the homologous challenge virus. Immunized mice were partially protected from lethal challenge with H5N1 virus or recombinant PR8-avN1. Sera transferred from immunized mice to naïve animals conferred similar protection against H5N1 mortality. Analysis of human sera showed that antibodies able to inhibit the sialidase activity of avN1 exist in some individuals. CONCLUSIONS: These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.

  17. Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated with IL-2, TGF-β and retinoic acid.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: Protective CD4+CD25+ regulatory T cells bearing the Forkhead Foxp3 transcription factor can now be divided into three subsets: Endogenous thymus-derived cells, those induced in the periphery, and another subset induced ex-vivo with pharmacological amounts of IL-2 and TGF-β. Unfortunately, endogenous CD4+CD25+ regulatory T cells are unstable and can be converted to effector cells by pro-inflammatory cytokines. Although protective Foxp3+CD4+CD25+ cells resistant to proinflammatory cytokines have been generated in mice, in humans this result has been elusive. Our objective, therefore, was to induce human naïve CD4+ cells to become stable, functional CD25+ Foxp3+ regulatory cells that were also resistant to the inhibitory effects of proinflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: The addition of the vitamin A metabolite, all-trans retinoic acid (atRA to human naïve CD4+ cells suboptimally activated with IL-2 and TGF-β enhanced and stabilized FOXP3 expression, and accelerated their maturation to protective regulatory T cells. AtRA, by itself, accelerated conversion of naïve to mature cells but did not induce FOXP3 or suppressive activity. The combination of atRA and TGF-β enabled CD4+CD45RA+ cells to express a phenotype and trafficking receptors similar to natural Tregs. AtRA/TGF-β-induced CD4+ regs were anergic and low producers of IL-2. They had potent in vitro suppressive activity and protected immunodeficient mice from a human-anti-mouse GVHD as well as expanded endogenous Tregs. However, treatment of endogenous Tregs with IL-1β and IL-6 decreased FOXP3 expression and diminished their protective effects in vivo while atRA-induced iTregs were resistant to these inhibitory effects. CONCLUSIONS/SIGNIFICANCE: We have developed a methodology that induces human CD4(+ cells to rapidly become stable, fully functional suppressor cells that are also resistant to proinflammatory cytokines. This methodology offers a practical