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Sample records for human enteric defensin

  1. Enteric alpha defensins in norm and pathology

    Lisitsyn Nikolai A

    2012-01-01

    Full Text Available Abstract Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.

  2. Candida Infections and Human Defensins.

    Polesello, Vania; Segat, Ludovica; Crovella, Sergio; Zupin, Luisa

    2017-01-01

    Candida species infections are an important worldwide health issue since they do not only affect immunocompromised patients but also healthy individuals. The host developed different mechanisms of protection against Candida infections; specifically the immune system and the innate immune response are the first line of defence. Defensis are a group of antimicrobial peptides, components of the innate immunity, produced at mucosal level and known to be active against bacteria, virus but also fungi. The aim of the current work was to review all previous studies in literature that analysed defensins in the context of Candida spp. infections, in order to investigate and clarify the exact mechanisms of defensins anti-fungal action. Several studies were identified from 1985 to 2017 (9 works form years 1985 to 1999, 44 works ranging from 2000 to 2009 and 35 from 2010 to 2017) searched in two electronic databases (PubMed and Google Scholar). The main key words used for the research were "Candida", "Defensins"," Innate immune system","fungi". The findings of the reviewed studies highlight the pivotal role of defensins antimicrobial peptides in the immune response against Candida infections, since they are able to discriminate host cell from fungi: defensins are able to recognize the pathogens cell wall (different in composition from the human ones), and to disrupt it through membrane permeabilization. However, further research is needed to explain completely defensins' mechanisms of action to fight C. albicans (and other Candida spp.) infections, being the information fragmentary and only in part elucidated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Gastrointestinal Autoimmunity Associated With Loss of Central Tolerance to Enteric alpha-Defensins

    Dobeš, Jan; Neuwirth, Aleš; Dobešová, Martina; Vobořil, Matouš; Balounová, Jana; Ballek, Ondřej; Lebl, J.; Meloni, A.; Krohn, K.; Kluger, N.; Ranki, A.; Filipp, Dominik

    2015-01-01

    Roč. 149, č. 1 (2015), s. 139-150 ISSN 0016-5085 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Enteric defensins * Intestinal autoimmunity * Mouse Model of APECED Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 18.187, year: 2015

  4. Conformational landscape and pathway of disulfide bond reduction of human alpha defensin

    Snijder, Joost; Van De Waterbeemd, Michiel; Glover, Matthew S.; Shi, Liuqing; Clemmer, David E.; Heck, Albert J R

    2015-01-01

    Human alpha defensins are a class of antimicrobial peptides with additional antiviral activity. Such antimicrobial peptides constitute a major part of mammalian innate immunity. Alpha defensins contain six cysteines, which form three well defined disulfide bridges under oxidizing conditions.

  5. Directional and balancing selection in human beta-defensins

    Armour John AL

    2008-04-01

    Full Text Available Abstract Background In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. Results We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93, is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Conclusion Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

  6. Directional and balancing selection in human beta-defensins.

    Hollox, Edward J; Armour, John A L

    2008-04-16

    In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.

  7. Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

    Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet

    2006-01-01

    Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...

  8. Human alpha-defensin-1 protects cells from intoxication with Clostridium perfringens iota toxin.

    Fischer, Stephan; Popoff, Michel R; Barth, Holger

    2018-03-01

    Iota toxin is produced by Clostridium perfringens type E strains and associated with diarrhea in cattle and lambs. This binary protein toxin comprises the enzyme component iota a (Ia), which ADP-ribosylates G-actin, and the separate transport component iota b (Ib), which delivers Ia into the cytosol of target cells. Ib binds to cell receptors and forms biologically active toxin complexes with Ia, which cause rounding of adherent cells due to the destruction of the actin cytoskeleton. Here, we report that the human peptide α-defensin-1 protects cultured cells including human colon cells from intoxication with iota toxin. In contrast, the related ß-defensin-1 had no effect, indicating a specific mode of action. The α-defensin-1 did not inhibit ADP-ribosylation of actin by Ia in vitro. Pretreatment of Ib with α-defensin-1 prior to addition of Ia prevented intoxication. Additionally, α-defensin-1 protected cells from cytotoxic effects mediated by Ib in the absence of Ia, implicating that α-defensin-1 interacts with Ib to prevent the formation of biologically active iota toxin on cells. In conclusion, the findings contribute to a better understanding of the functions of α-defensin-1 and suggest that this human peptide might be an attractive starting point to develop novel pharmacological options to treat/prevent diseases associated with iota toxin-producing Clostridium perfringens strains.

  9. Characterization of Cimex lectularius (bedbug) defensin peptide and its antimicrobial activity against human skin microflora.

    Kaushal, Akanksha; Gupta, Kajal; van Hoek, Monique L

    2016-02-19

    Antimicrobial peptides are components of both vertebrate and invertebrate innate immune systems that are expressed in response to exposure to bacterial antigens. Naturally occurring antimicrobial peptides from evolutionarily ancient species have been extensively studied and are being developed as potential therapeutics against antibiotic resistant microorganisms. In this study, a putative Cimex lectularius (bedbug, CL) defensin is characterized for its effectiveness against human skin flora including Gram-negative and Gram-positive bacteria. The bedbug defensin (CL-defensin), belonging to family of insect defensins, is predicted to have a characteristic N-terminal loop, an α-helix, and an antiparallel β-sheet, which was supported by circular dichroism spectroscopy. The defensin was shown to be antimicrobial against Gram-positive bacteria commonly found on human skin (Micrococcus luteus, Corynebacterium renale, Staphylococcus aureus and Staphylococcus epidermidis); however, it was ineffective against common skin Gram-negative bacteria (Pseudomonas aeruginosa and Acinetobacter baumannii) under low-salt conditions. CL-defensin was also effective against M. luteus and C. renale in high-salt (MIC) conditions. Our studies indicate that CL-defensin functions by depolarization and pore-formation in the bacterial cytoplasmic membrane. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

    Hartshorn, Kevan L.; White, Mitchell R.; Tecle, Tesfaldet

    2006-01-01

    Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characte......Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study...... was to characterize antiviral interactions between SP-D and HNPs. Recombinant and/or natural forms of SP-D and related collectins and HNPs were tested for antiviral activity against two different strains of IAV. HNPs 1 and 2 did not inhibit viral hemagglutination activity, but they interfered...... with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some...

  11. Defensins in periodontal health

    Taran Bedi

    2015-01-01

    Full Text Available Defensins are abundant and widely distributed peptides in human and animal tissues that are involved in host defence. Defensins not only have the ability to strengthen the innate immune system but can also enhance the adaptive immune system by chemotaxis of monocytes, T-lymphocytes, dendritic cells and mast cells to the infection site. Defensins also improves the capacity of macrophage phagocytosis. A greater understanding of how these peptides act in the healthy, gingivitis and periodontitis conditions would definitely open new opportunities for identification, prevention and treatment of periodontal diseases. This discussion focuses on recent studies about biological function of defensins in human diseases and animal models.

  12. High level expression of human epithelial β-defensins (hBD-1, 2 and 3 in papillomavirus induced lesions

    Chong Kong T

    2006-09-01

    Full Text Available Abstract Background Epithelial defensins including human β-defensins (hBDs and α-defensins (HDs are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. Results Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p Conclusion Human β-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

  13. Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

    Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

    2013-06-01

    The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

  14. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

    Peschel, A.; Jack, R.W.; Otto, M.; Collins, L.V.; Staubitz, P.; Nicholson, G.; Kalbacher, H.; Nieuwenhuizen, W.F.; Jung, G.; Tarkowski, A.; Kessel, K.P.M. van; Strijp, J.A.G. van

    2001-01-01

    Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance

  15. [Study on vaginal production of human defensins and the correlated pathogenetic factors of vulvovaginal candidiasis].

    Wang, Wen; DI, Wen; Liao, Qin-ping; Liu, Zhao-hui; Zhang, Ning; Zhang, Hui-ying; Zhang, Dai; Geng, Li; Fan, Shang-rong; Hu, Li-na

    2008-07-01

    To investigate the correlated pathogenetic factors and vaginal local immunity in vulvovaginal candidiasis (VVC). A case control study was conducted to compare VVC group (60 cases) with normal group (60 cases). All of the women filled up the specific questionnaires. Routine examination, pH test and bacterial culture were done on the vaginal discharge. Cytokines of the vaginal lavage were measured by enzyme linked immunosorbent assay. (1) Outcomes of the questionnaires: there was no significant difference between the two groups in educational background, knowledge of gynecologic infection, history of gynecologic infection, hygienic habit, sex life, or use of medicine (P > 0.05). The incidence of chronic cervicitis in normal group (43%, 26/60) was higher than in VVC group (22%, 13/60; P vaginal pH between the two groups (P > 0.05). (3) Detection rate of candida albicans by vaginal discharge routine examination was 72% (43/60). (4) The concentrations of interleukin (IL) 2, and IL-4 in vaginal lavage did not show significant difference between the two groups (P > 0.05), but the concentrations of human defensin 5, human beta-defensin (HBD) 1, and HBD2 in VVC group [(0.94 +/- 0.44) mg/L, (3.1 +/- 0.4) microg/L, (10 +/- 6) microg/L] were higher than normal group (P < 0.05). VVC is a common vulvovaginitis. There is no significant correlation between the incidence of VVC and educational background, knowledge of gynecologic infection, history of gynecologic infection, hygienic habit, sex life, or use of medicine in the child-bearing period. Human defensin may be closely correlated with the pathogenesis of VVC.

  16. Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

    Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

    2012-01-01

    Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

  17. The Yin and Yang of human beta defensins in health and disease

    Aaron eWeinberg

    2012-10-01

    Full Text Available Rapidly evolving research examining the extended role of human beta-defensins (hBDs in chemoattraction, innate immune-mediated response and promotion of angiogenesis suggest that the collective effects of hBDs extend well beyond their antimicrobial mechanism(s. Indeed, the numerous basic cellular functions associated with hBDs demonstrate that these peptides have dual impact on health, as they may be advantageous under certain conditions, but potentially detrimental in others. The consequences of these functions are reflected in the overexpression of hBDs in diseases, such as psoriasis, and recently the association of hBDs with pro-tumoral signaling. The mechanisms regulating hBD response in health and disease are still being elucidated. Clearly the spectrum of function now attributed to hBD regulation identifies these molecules as important cellular regulators, whose appropriate expression is critical for proper immune surveillance; i.e., expression of hBDs in proximity to areas of cellular dysregulation may inadvertently exacerbate disease progression. Understanding the mechanism(s that regulate contextual signaling of hBDs is an important area of concentration in our laboratories. Using a combination of immunologic, biochemical and molecular biologic approaches, we have identified signaling pathways associated with hBD promotion of immune homeostasis and have begun to dissect the inappropriate role that beta-defensins may assume in disease.

  18. Allelic recombination between distinct genomic locations generates copy number diversity in human β-defensins

    Bakar, Suhaili Abu; Hollox, Edward J.; Armour, John A. L.

    2009-01-01

    β-Defensins are small secreted antimicrobial and signaling peptides involved in the innate immune response of vertebrates. In humans, a cluster of at least 7 of these genes shows extensive copy number variation, with a diploid copy number commonly ranging between 2 and 7. Using a genetic mapping approach, we show that this cluster is at not 1 but 2 distinct genomic loci ≈5 Mb apart on chromosome band 8p23.1, contradicting the most recent genome assembly. We also demonstrate that the predominant mechanism of change in β-defensin copy number is simple allelic recombination occurring in the interval between the 2 distinct genomic loci for these genes. In 416 meiotic transmissions, we observe 3 events creating a haplotype copy number not found in the parent, equivalent to a germ-line rate of copy number change of ≈0.7% per gamete. This places it among the fastest-changing copy number variants currently known. PMID:19131514

  19. Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells

    Park Raekil

    2006-01-01

    Full Text Available Abstract Background We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi and that interleukin 1 alpha (IL-1 alpha up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. Methods The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM. Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. Results Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. Conclusion We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway.

  20. Human α-defensin (DEFA) gene expression helps to characterise benign and malignant salivary gland tumours

    Winter, Jochen; Wenghoefer, Matthias; Pantelis, Annette; Kraus, Dominik; Reckenbeil, Jan; Reich, Rudolf; Jepsen, Soeren; Fischer, Hans-Peter; Allam, Jean-Pierre; Novak, Natalija

    2012-01-01

    Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy. Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining. Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours – except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands. A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin’s tumour

  1. Accurate measurement of gene copy number for human alpha-defensin DEFA1A3.

    Khan, Fayeza F; Carpenter, Danielle; Mitchell, Laura; Mansouri, Omniah; Black, Holly A; Tyson, Jess; Armour, John A L

    2013-10-20

    Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing. In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples. We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn's disease, type I diabetes, HIV progression and multiple sclerosis.

  2. The Effect of Calcipotriol on the Expression of Human β Defensin-2 and LL-37 in Cultured Human Keratinocytes

    Beom Joon Kim

    2009-01-01

    Full Text Available Background. Vitamin D has been reported to regulate innate immunity by controlling the expression of antimicrobial peptides (AMPs. Objective. We investigated the effect of calcipotriol on the expression of AMPs in human cultured keratinocytes. Methods. Keratinocytes were treated with lipopolysaccharide (LPS, TNF-α, Calcipotriol and irradiated with UVB, cultured, and harvested. To assess the expression of human beta defensin-2 and LL-37 in the control group, not exposed to any stimulants, the experimental group was treated with LPS, TNF-α, or UVB, and another group was treated again with calcipotriol; reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical staining were performed. Results. In the experimental group treated with LPS, UVB irradiation, and TNF-α, the expression of β-defensin and LL-37 was increased more than in the control group and then decreased in the experimental group treated with calcipotriol. Conclusions. Calcipotriol suppressed HBD-2 and LL-37, which were stimulated by UVB, LPS, and TNF-α.

  3. α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome

    Mayim E. Wiens

    2017-01-01

    Full Text Available α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5 blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses.

  4. Human β-defensin 3 inhibits periodontitis development by suppressing inflammatory responses in macrophages.

    Cui, Di; Lyu, Jinglu; Li, Houxuan; Lei, Lang; Bian, Tianying; Li, Lili; Yan, Fuhua

    2017-11-01

    Human β-defensin 3 (hBD3) is a cationic peptide with immunomodulatory effects on both innate and acquired immune responses. Periodontitis, an inflammatory disease that extends deep into periodontal tissues, causes the loss of supporting structures around the tooth. The present study assessed the effects of hBD3 as a monotherapy for periodontitis in mice and explored its potential mechanism. In vivo, hBD3 inhibited the levels of tumour necrosis factor (TNF)-α, interleukin-6, and matrix metalloprotease-9 in periodontium exposed to Porphyromonas gingivalis (P.g) in a mouse periodontitis model; reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, hBD3 was related to the expression of polarization signature molecules in circulating monocytes. In vitro, hBD3 notably suppressed the production of TNF-α and interleukin-6 in RAW 264.7 cells stimulated by the lipopolysaccharide of P.g. Moreover, hBD3 attenuated polarization of RAW 264.7 cells into the M1 phenotype, with reduced activation of nuclear factor-κB signal transduction. In conclusion, hBD3 exhibits potent anti-periodontitis properties both in vitro and in vivo, and this effect may be correlated to inhibition of the nuclear factor-κB pathway and macrophage polarization. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Effects of Genetically Modified Milk Containing Human Beta-Defensin-3 on Gastrointestinal Health of Mice.

    Xin Chen

    Full Text Available This study was performed to investigate the effects of genetically modified (GM milk containing human beta-defensin-3 (HBD3 on mice by a 90-day feeding study. The examined parameters included the digestibility of GM milk, general physical examination, gastric emptying function, intestinal permeability, intestinal microflora composition of mice, and the possibility of horizontal gene transfer (HGT. The emphasis was placed on the effects on gastrointestinal (GI tract due to the fact that GI tract was the first site contacting with food and played crucial roles in metabolic reactions, nutrition absorption and immunity regulation in the host. However, the traditional methods for analyzing the potential toxicological risk of GM product pay little attention on GI health. In this study, the results showed GM milk was easy to be digested in simulated gastric fluid, and it did not have adverse effects on general and GI health compared to conventional milk. And there is little possibility of HGT. This study may enrich the safety assessment of GM product on GI health.

  6. Increased expression and levels of human β defensins (hBD2 and hBD4 in adults with dental caries

    Girolamo Jose Barrera

    2013-09-01

    Full Text Available Introduction: Defensins are small anti-microbial peptides produced by epithelial cells. These peptides have a broad range of actions against microorganisms, including Gram-positive and Gram-negative bacteria.Human defensins are classifi ed into two subfamilies, the α-, and β- defensins, which differ in their distribution of disulphide bonds between the six conserved cysteine residues. Defensins are found in salivaand others compartments of the body. Human β defensins 2 (hBD2, beta defensins 4 (hBD4 and alpha defensins 4 (hNP4 in saliva may contributes to vulnerability or resistance to caries. This study aimed to determine a possible correlation between caries and levels of defensins measuring the expression in gingival tissue and concentrations in saliva samples.Methods: Oral examinations were performed on 100 adults of both genders (18-30 years old, and unstimulated whole saliva was collected for immunoassays of the three peptides and for the salivary pH, buffercapacity, protein, and peroxidase activity. mRNA levels of defensins in gingival sample were assessed by semi-quantitative RT-PCR technique.Results: The median salivary levels of hBD2 and hBD4 were 1.88 μg/ml and 0.86 μg/ml respectively for the caries-free group (n=44 and 7.26 μ/ml (hBD2 and 4.25 μg/ml (hBD4 for all subjects with evidenceof caries (n=56. There was no difference in the levels of hNP4, salivary pH, and proteins between groups, however the peroxidase activity and buffer capacity (interval 6.0-5.0 were reduced in caries group. Transcriptional levels of hBD2 and hBD4 did correlate with caries experience, the mRNA expression of hBD2 and hBD4 were signifi cantly higher in patients with caries than in patients with no-caries (p Conclusion: We conclude that high salivary levels and expression of beta defensins, low peroxidase activity and buffer capacity may represent a biological response of oral tissue to caries. Our observation couldlead to new ways to prevent caries

  7. Increased expression and levels of human β defensins (hBD2 and hBD4 in adults with dental caries

    Girolamo Jose Barrera

    2013-09-01

    Full Text Available Introduction: Defensins are small anti-microbial peptides produced by epithelial cells. These peptides have a broad range of actions against microorganisms, including Gram-positive and Gram-negative bacteria.Human defensins are classifi ed into two subfamilies, the α-, and β- defensins, which differ in their distribution of disulphide bonds between the six conserved cysteine residues. Defensins are found in salivaand others compartments of the body. Human β defensins 2 (hBD2, beta defensins 4 (hBD4 and alpha defensins 4 (hNP4 in saliva may contributes to vulnerability or resistance to caries. This study aimed to determine a possible correlation between caries and levels of defensins measuring the expression in gingival tissue and concentrations in saliva samples.Methods: Oral examinations were performed on 100 adults of both genders (18-30 years old, and unstimulated whole saliva was collected for immunoassays of the three peptides and for the salivary pH, buffercapacity, protein, and peroxidase activity. mRNA levels of defensins in gingival sample were assessed by semi-quantitative RT-PCR technique.Results: The median salivary levels of hBD2 and hBD4 were 1.88 μg/ml and 0.86 μg/ml respectively for the caries-free group (n=44 and 7.26 μ/ml (hBD2 and 4.25 μg/ml (hBD4 for all subjects with evidenceof caries (n=56. There was no difference in the levels of hNP4, salivary pH, and proteins between groups, however the peroxidase activity and buffer capacity (interval 6.0-5.0 were reduced in caries group. Transcriptional levels of hBD2 and hBD4 did correlate with caries experience, the mRNA expression of hBD2 and hBD4 were signifi cantly higher in patients with caries than in patients with no-caries (p < 0.01.Conclusion: We conclude that high salivary levels and expression of beta defensins, low peroxidase activity and buffer capacity may represent a biological response of oral tissue to caries. Our observation couldlead to new ways to prevent

  8. The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

    Andreas Bayer; Justus Lammel; Mersedeh Tohidnezhad; Sebastian Lippross; Peter Behrendt; Tim Klüter; Thomas Pufe; Jochen Cremer; Holger Jahr; Franziska Rademacher; Regine Gläser; Jürgen Harder

    2017-01-01

    Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF?)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting acti...

  9. Oviduct-Specific Expression of Human Neutrophil Defensin 4 in Lentivirally Generated Transgenic Chickens

    Liu, Tongxin; Wu, Hanyu; Cao, Dainan; Li, Qingyuan; Zhang, Yaqiong; Li, Ning; Hu, Xiaoxiang

    2015-01-01

    The expression of oviduct-specific recombinant proteins in transgenic chickens is a promising technology for the production of therapeutic biologics in eggs. In this study, we constructed a lentiviral vector encoding an expression cassette for human neutrophil defensin 4 (HNP4), a compound that displays high activity against Escherichia coli, and produced transgenic chickens that expressed the recombinant HNP4 protein in egg whites. After the antimicrobial activity of the recombinant HNP4 protein was tested at the cellular level, a 2.8-kb ovalbumin promoter was used to drive HNP4 expression specifically in oviduct tissues. From 669 injected eggs, 218 chickens were successfully hatched. Ten G0 roosters, with semens identified as positive for the transgene, were mated with wild-type hens to generate G1 chickens. From 1,274 total offspring, fifteen G1 transgenic chickens were positive for the transgene, which was confirmed by PCR and Southern blotting. The results of the Southern blotting and genome walking indicated that a single copy of the HNP4 gene was integrated into chromosomes 1, 2, 3, 4, 6 and 24 of the chickens. As expected, HNP4 expression was restricted to the oviduct tissues, and the levels of both transcriptional and translational HNP4 expression varied greatly in transgenic chickens with different transgene insertion sites. The amount of HNP4 protein expressed in the eggs of G1 and G2 heterozygous transgenic chickens ranged from 1.65 μg/ml to 10.18 μg/ml. These results indicated that the production of transgenic chickens that expressed HNP4 protein in egg whites was successful. PMID:26020529

  10. Antibacterial Activity of Four Human Beta-Defensins: HBD-19, HBD-23, HBD-27, and HBD-29

    David Camerini

    2012-03-01

    Full Text Available Human β-defensins (HBD are a family of small antimicrobial peptides that play important roles in the innate and adaptive immune defenses against microbial infection. In this study, we predicted the mature sequences and assessed the antibacterial properties of synthetic HBD-19, HBD-23, HBD-27, and HBD-29 against three species of clinically relevant bacteria: Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. We also examined the cytotoxicity of each β-defensin to human cells. HBD-19 exhibited modest antibacterial effects against E. coli and S. aureus but had little effect on the growth of P. aeruginosa. HBD-23 exhibited substantial antibacterial effects against all three bacterial species and was particularly potent against the Gram-negative species, E. coli and P. aeruginosa. HBD-27 exerted modest antibacterial activity only towards S. aureus while HBD-29 had modest antibacterial activity for E. coli and P. aeruginosa. HBD-23 and HBD-27 showed little or no toxicity to human peripheral blood mononuclear cells, while HBD-19 and HBD-29 decreased cell viability by 20% at 30 μg/mL.

  11. Role of urinary cathelicidin LL-37 and human β-defensin 1 in uncomplicated Escherichia coli urinary tract infections

    Nielsen, Karen L; Dynesen, Pia; Larsen, Preben

    2014-01-01

    Cathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicated Escherichia coli urinary tract infections (UTIs). This was investiga......Cathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicated Escherichia coli urinary tract infections (UTIs......). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 and in vivo virulence. Forty-seven UTI patients and 50 controls who had never had a UTI were...... included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecal E. coli clones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D). In vivo virulence was investigated in the murine UTI model by use of selected fecal...

  12. Utilization of plant-derived recombinant human β-defensins (hBD-1 and hBD-2) for averting salmonellosis.

    Patro, Sunita; Maiti, Soumitra; Panda, Santosh Kumar; Dey, Nrisingha

    2015-04-01

    We describe the use of plant-made β-defensins as effective antimicrobial substances for controlling salmonellosis, a deadly infection caused by Salmonella typhimurium (referred to further as S. typhi). Human β-defensin-1 (hBD-1) and -2 (hBD-2) were expressed under the control of strong constitutive promoters in tobacco plants, and bio-active β-defensins were successfully extracted. In the in vitro studies, enriched recombinant plant-derived human β-defensin-1 (phBD-1) and -2 (phBD-2) obtained from both T1 and T2 transgenic plants showed significant antimicrobial activity against Escherichia coli and S. typhi when used individually and in various combinations. The 2:1 peptide combination of phBD-1:phBD-2 with peptides isolated from T1-and T2-generation plants reduced the growth of S. typhi by 96 and 85 %, respectively. In vivo studies employing the mouse model (Balb/c) of Salmonella infection clearly demonstrated that the administration of plant-derived defensins individually and in different combinations enhanced the mean survival time of Salmonella-infected animals. When treatment consisted of the 2:1 phBD-1:phBD-2 combination, approximately 50 % of the infected mice were still alive at 206 h post-inoculation; the lowest number of viable S. typhi was observed in the liver and spleen of infected animals. We conclude that plant-made recombinant β-defensins (phBD-1 and phBD-2) are promising antimicrobial substances and have the potential to become additional tools against salmonellosis, particularly when used in combination.

  13. Identification of sociodemographic and clinical factors associated with the levels of human β-defensin-1 and human β-defensin-2 in the human milk of Han Chinese.

    Wang, Xiao-Fang; Cao, Rui-Ming; Li, Jing; Wu, Jing; Wu, Sheng-Mei; Chen, Tong-Xin

    2014-03-14

    Human milk provides infants with various immune molecules. The objective of the present study was to measure human β-defensin-1 (hBD-1) and human β-defensin-2 (hBD-2) levels in the colostrum and mature milk of healthy Han Chinese, to identify factors regulating milk hBD-1 and hBD-2 expression and to explore the potential protective effect of milk hBD-1 and hBD-2 on infants. A total of 100 mothers and their babies were recruited into the study. Sociodemographic characteristics and other factors were obtained by a questionnaire. Babies were followed up for a period of 6 months. Colostrum samples (n 100) and mature milk samples (n 82) were collected by hand expression. The hBD-1 and hBD-2 concentrations were measured by ELISA. The hBD-1 and hBD-2 levels differed in the colostrum and mature milk. In the colostrum, the concentration ranges of hBD-1 and hBD-2 were 1·04-12·81 μg/ml and 0·31-19·12 ng/ml, respectively. In mature milk, the hBD-1 and hBD-2 levels were 1·03-31·76 ng/ml and 52·65-182·29 pg/ml, respectively. Several independent factors influence their production. The multivariable analysis showed a strong association between pre-pregnancy BMI and hBD-1 levels in the colostrum (P=0·001), mode of delivery was significantly associated with hBD-2 levels in the colostrum (P=0·006) and gestational age was significantly associated with hBD-1 levels in mature milk (P= 0·010). During the first 6 months of life, the incidence rate of upper respiratory infection was found to be less in the high-colostrum hBD-1 group than in the low-colostrum hBD-1 group (χ²=4·995, P=0·025). The present study suggested that the abundance of hBD-1 in the colostrum may have a protective function against upper respiratory infection for infants younger than 6 months.

  14. Expression and purification of moricin CM4 and human β-defensins 4 in Escherichia coli using a new technology.

    Shen, Yang; Ai, Hong-Xin; Song, Ren; Liang, Zhen-Ning; Li, Jian-Feng; Zhang, Shuang-Quan

    2010-10-20

    Different strategies have been developed to produce small antimicrobial peptides using recombinant techniques. Here we report a new technology of biosynthesis of moricin CM4 and human β-defensins 4 (HβD4) in the Escherichia coli. The CM4 and HβD4 gene were cloned into a vector containing the tags elastin-like peptide (ELP) and intein to construct the expression vector pET-EI-CM4 and pET-EI-HβD4. All the peptides, expressed as soluble fusions, were isolated from the protein debris by the method called inverse transition cycling (ITC) rather than traditional immobilized metal affinity chromatography (IMAC) and separated from the fusion leader by self-cleavage. Fully reduced peptides that were purified exhibited expected antimicrobial activity. The approach described here is a low-cost, convenient and potential way for generating small antimicrobial peptide. Copyright © 2010 Elsevier GmbH. All rights reserved.

  15. Human β-Defensin 3 Reduces TNF-α-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells

    Tianying Bian

    2017-01-01

    Full Text Available The aim of this study was to investigate the role of human β-defensin 3 (hBD3 in the initiation stage of atherosclerosis with human umbilical vein endothelial cells (HUVECs triggered by tumor necrosis factor- (TNF- α. The effects of hBD3 on TNF-α-induced endothelial injury and inflammatory response were evaluated. Our data revealed that first, hBD3 reduced the production of interleukin-6 (IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1, and macrophage migration inhibitory factor (MIF in HUVECs in a dose-dependent manner. In addition, hBD3 significantly prevented intracellular reactive oxygen species (ROS production by HUVECs. Second, western blot analysis demonstrated that hBD3 dose-dependently suppressed the protein levels of intracellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 in TNF-α-induced HUVECs. As a result, hBD3 inhibited monocyte adhesion to TNF-α-treated endothelial cells. Additionally, hBD3 suppressed TNF-α-induced F-actin reorganization in HUVECs. Third, hBD3 markedly inhibited NF-κB activation by decreasing the phosphorylation of IKK-α/β, IκB, and p65 subunit within 30 min. Moreover, the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK in the mitogen-activated protein kinase (MAPK pathway were also inhibited by hBD3 in HUVECs. In conclusion, hBD3 exerts anti-inflammatory and antioxidative effects in endothelial cells in response to TNF-α by inhibiting NF-κB and MAPK signaling.

  16. Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

    Abdelhabib Semlali

    Full Text Available The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4 and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs and the potential development of colon cancer.

  17. Salivary human beta defensins affected by oral Candida status in Chinese HIV/AIDS patients undergoing ART.

    Liu, Zhenmin; Yong, Xiangzhi; Jiang, Lanlan; Zhang, Linlin; Lin, Xuefang; Liu, Wei; Peng, Yuanyuan; Tao, Renchuan

    2018-03-02

    To observe relationships between oral Candida status and salivary human beta defensin-2 and -3 (hBD-2 and hBD-3) levels in HIV/AIDS patients of Guangxi, China during the first year of antiretroviral therapy (ART) dynamically, and to understand the influence of ART on oral Candida status and salivary hBDs expressions. A prospective self-controlled study was carried to observe the dynamic changes of CD4 + T cell counts, oral Candida carriages and salivary hBD-2,3 expressions in HIV/AIDS patients during the first year of ART. A total of 90 HIV/AIDS patients were enrolled, and were examined at the baseline, 3rd, 6th, 12th month of ART. Thirty healthy individuals were enrolled as control. Peripheral blood, oral rinse sample and unstimulated whole saliva were collected to test CD4 + T cell counts, oral Candida carriages and hBD-2,3 expressions. In the first year of ART, CD4 + T cell counts increased significantly. However, oral Candida carriages and oral candidiasis decreased significantly, and salivary hBD-2 expressions in HIV/AIDS patients decreased gradually, salivary hBD-3 levels were highly variable. Salivary hBD-2 concentrations were positively related to oral Candida carriages. The incidence of oral candidiasis among HIV/AIDS patients gradually decreased due to the immune reconstruction of ART. Salivary defensins might play an important role in Candida-host interaction in HIV/AIDS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

    Andreas Bayer

    2017-01-01

    Full Text Available Platelet-released growth factors (PRGF and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF® contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3 is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR. In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.

  19. The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

    Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

    2017-01-01

    Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

  20. Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human β-defensins 2 and 3.

    Spudy, Björn; Sönnichsen, Frank D; Waetzig, Georg H; Grötzinger, Joachim; Jung, Sascha

    2012-10-12

    Antimicrobial peptides participate in the first line of defence of many organisms against pathogens. In humans, the family of β-defensins plays a pivotal role in innate immunity. Two human β-defensins, β-defensin-2 and -3 (HBD2 and HBD3), show substantial sequence identity and structural similarity. However, HBD3 kills Staphylococcus (S.) aureus with a 4- to 8-fold higher efficiency compared to HBD2, whereas their activities against Escherichia (E.) coli are very similar. The generation of six HBD2/HBD3-chimeric molecules led to the identification of distinct molecular regions which mediate their divergent killing properties. One of the chimeras (chimera C3) killed both E. coli and S. aureus with an even higher efficacy compared to the wild-type molecules. Due to the broad spectrum of its antimicrobial activity against many human multidrug-resistant pathogens, this HBD2/HBD3-chimeric peptide represents a promising candidate for a new class of antibiotics. In order to investigate the structural basis of its exceptional antimicrobial activity, the peptide's tertiary structure was determined by NMR spectroscopy, which allowed its direct comparison to the published structures of HBD2 and HBD3 and the identification of the activity-increasing molecular features. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

    Kabeerdoss Jayakanthan

    2011-12-01

    Full Text Available Abstract Background Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. Findings 26 women aged 18-21 (median 19 years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (109 in 200 ml for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184 and returned to normal after cessation of probiotic yoghurt intake. Conclusions Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  2. Generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to Mycobacterium bovis infection.

    Su, Feng; Wang, Yongsheng; Liu, Guanghui; Ru, Kun; Liu, Xin; Yu, Yuan; Liu, Jun; Wu, Yongyan; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-03-01

    Bovine tuberculosis results from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis family. Worldwide, M. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. Generating M. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing M. bovis infections. In this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding human β-defensin 3 (HBD3), which confers resistance to mycobacteria in vitro. We first generated alveolar epithelial cells expressing HBD3 under the control of the bovine MUC1 promoter, and confirmed that these cells secreted HBD3 and possessed anti-mycobacterial capacity. We then generated and identified transgenic cattle by somatic cell nuclear transfer. The cleavage and blastocyst formation rates of genetically modified embryos provided evidence that monoclonal transgenic bovine fetal fibroblast cells have an integral reprogramming ability that is similar to that of normal cells. Five genetically modified cows were generated, and their anti-mycobacterial capacities were evaluated. Alveolar epithelial cells and macrophages from these cattle expressed higher levels of HBD3 protein compared with non-transgenic cells and possessed effective anti-mycobacterial capacity. These results suggest that the overall risk of M. bovis infection in transgenic cattle is efficiently reduced, and support the development of genetically modified animals as an effective tool to reduce M. bovis infection. © 2016 Federation of European Biochemical Societies.

  3. Comparing the efficiency of Er,Cr:YSGG laser and diode laser on human β-defensin-1 and IL-1β levels during the treatment of generalized aggressive periodontitis and chronic periodontitis.

    Ertugrul, Abdullah Seckin; Tekin, Yasin; Talmac, Ahmet Cemil

    2017-11-01

    The aim of this study is to determine the suitability of the Er,Cr:YSGG and 940 ± 15-nm diode laser for the treatment of generalized aggressive periodontitis and chronic periodontitis by measuring the levels of human β-defensin-1 and IL-1β. A total of 26 patients were included in this study. The study was designed as a "split-mouth" experiment. We performed scaling and root planing in the right maxillary quadrant, scaling and root planning + Er,Cr:YSGG laser in the left maxillary quadrant, scaling and root planning + 940 ± 15-nm diode laser in the left mandibular quadrant, and only scaling and root planing in the right mandibular quadrant. The presence of human β-defensin-1 and IL-1β was analyzed with an ELISA. When the baseline and post-treatment human β-defensin-1 levels and IL-1β levels of the study groups were evaluated, a decrease in human β-defensin-1 and IL-1β were observed in the quadrant where the Er,Cr:YSGG laser was applied in both the generalized aggressive periodontitis group and the chronic periodontitis group. The use of the Er,Cr:YSGG laser at non-surgical periodontal treatment decreased both IL-1β and human β-defensin-1 levels. It is likely that Er,Cr:YSGG laser is more suitable for the treatment of generalized aggressive periodontitis and chronic periodontitis.

  4. Human β-defensin 2 may inhibit internalisation of bacillus Calmette-Guérin (BCG) in bladder cancer cells.

    Kim, Jung Hoon; Kim, Soon-Ja; Lee, Kyung Mee; Chang, In Ho

    2013-10-01

    To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells. Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments. BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells. © 2013 The Authors. BJU International © 2013 BJU International.

  5. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

    Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

    2017-09-01

    Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

  6. Diesel exhaust particles increase IL-1β-induced human β-defensin expression via NF-κB-mediated pathway in human lung epithelial cells

    Lee Chun

    2006-05-01

    Full Text Available Abstract Background Human β-defensin (hBD-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8 expression to DEP exposure in interleukin-1 beta (IL-1β-stimulated A549 cells. Results IL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway. Conclusion These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.

  7. Defensins from the tick Ixodes scapularis are effective against phytopathogenic fungi and the human bacterial pathogen Listeria grayi

    Tonk, Miray; Cabezas-Cruz, A.; Valdés, James J.; Rego, Ryan O. M.; Chrudimská, Tereza; Strnad, Martin; Šíma, Radek; Bell-Sakyi, L.; Franta, Z.; Vilcinskas, A.; Grubhoffer, Libor; Rahnamaeian, M.

    2014-01-01

    Roč. 7, DEC 3 2015 (2014), s. 554 ISSN 1756-3305 R&D Projects: GA ČR(CZ) GAP302/11/1901; GA MŠk(CZ) EE2.3.30.0032; GA ČR GP13-12816P Institutional support: RVO:60077344 Keywords : Antimicrobial peptide * Defensin * Listeria grayi * Fusarium spp * Ixodes scapularis * Tick cell line Subject RIV: EE - Microbiology, Virology Impact factor: 3.430, year: 2014

  8. Periodontopathogens and human β-defensin-2 expression in gingival crevicular fluid from patients with periodontal disease in Guangxi, China.

    Yong, X; Chen, Y; Tao, R; Zeng, Q; Liu, Z; Jiang, L; Ye, L; Lin, X

    2015-06-01

    Periodontal diseases are often induced by periodontopathogens, which are always exposed to certain innate immune factors in gingival crevicular fluid, including human β-defensin-2 (hBD-2). This study aims to investigate the relationship among periodontopathogens, clinical parameters and hBD-2 expression. Thirty-two healthy controls, 42 patients with chronic gingivitis and 95 patients with chronic periodontitis were recruited in Guangxi, China. Bleeding index, probing depth and clinical attachment level were measured for all teeth including mesiobuccal, buccal, disobuccal, mesiolingual, lingual, disolingual six sites of all patient. Gingival crevicular fluid samples were collected from the study sites. The prevalence and copy numbers (CN) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia and total bacteria in gingival crevicular fluid were quantified by real-time PCR. The hBD-2 concentration in gingival crevicular fluid was measured by ELISA. Both the prevalence and the CN of A. actinomycetemcomitans, P. gingivalis, T. denticola and T. forsythia were higher in patients with chronic periodontitis than in healthy controls and patients with chronic gingivitis; however, there was no significant difference in the prevalence of P. intermedia among the three study groups, and the highest CN was found in patients with chronic gingivitis, rather than in patients with chronic periodontitis. The loads of P. gingivalis, P. intermedia, T. denticola and total bacteria were positively related to probing depth, bleeding index and clinical attachment level. The concentration of hBD-2 in gingival crevicular fluid was higher in patients with chronic gingivitis and in patients with chronic periodontitis than in healthy controls. In addition, the hBD-2 concentration was positively related to the CN of P. gingivalis, T. forsythia and total bacteria, as well as to bleeding index and probing depth. The

  9. Defensins: The Case for Their Use against Mycobacterial Infections

    Haodi Dong

    2016-01-01

    Full Text Available Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides produced by a number of cell types, most notably neutrophil granulocytes and epithelial cells. All three defensin types (α-, β-, and θ-defensins have antibacterial activities, mainly through bacterial membrane permeabilization. Defensins are effective against Gram-negative and Gram-positive bacteria including mycobacteria and are active both intra- and extracellularly. Mycobacterial resistance has never been demonstrated although the mprF gene encoding resistance in Staphylococcus aureus is present in the Mycobacterium tuberculosis genome. In addition to their antibacterial effect, defensins are chemoattractants for macrophages and neutrophils. There are many cases for their use for therapy or prophylaxis in tuberculosis as well. In conclusion, we propose that there is considerable scope and potential for exploring their use as therapeutic/prophylactic agents and more comprehensive survey of defensins from different species and their bioactivity is timely.

  10. Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

    Lee JY

    2015-08-01

    Full Text Available Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to

  11. Grape seed extract for control of human enteric viruses.

    Su, Xiaowei; D'Souza, Doris H

    2011-06-01

    Grape seed extract (GSE) is reported to have many pharmacological benefits, including antioxidant, anti-inflammatory, anticarcinogenic, and antimicrobial properties. However, the effect of this inexpensive rich source of natural phenolic compounds on human enteric viruses has not been well documented. In the present study, the effect of commercial GSE, Gravinol-S, on the infectivity of human enteric virus surrogates (feline calicivirus, FCV-F9; murine norovirus, MNV-1; and bacteriophage MS2) and hepatitis A virus (HAV; strain HM175) was evaluated. GSE at concentrations of 0.5, 1, and 2 mg/ml was individually mixed with equal volumes of each virus at titers of ∼7 log(10) PFU/ml or ∼5 log(10) PFU/ml and incubated for 2 h at room temperature or 37°C. The infectivity of the recovered viruses after triplicate treatments was evaluated by standardized plaque assays. At high titers (∼7 log(10) PFU/ml), FCV-F9 was significantly reduced by 3.64, 4.10, and 4.61 log(10) PFU/ml; MNV-1 by 0.82, 1.35, and 1.73 log(10) PFU/ml; MS2 by 1.13, 1.43, and 1.60 log(10) PFU/ml; and HAV by 1.81, 2.66, and 3.20 log(10) PFU/ml after treatment at 37°C with 0.25, 0.50, and 1 mg/ml GSE, respectively (P PFU/ml) at 37°C also showed viral reductions. Room-temperature treatments with GSE caused significant reduction of the four viruses, with higher reduction for low-titer FCV-F9, MNV-1, and HAV compared to high titers. Our results indicate that GSE shows promise for application in the food industry as an inexpensive novel natural alternative to reduce viral contamination and enhance food safety.

  12. Detection methods for human enteric viruses in representative foods.

    Leggitt, P R; Jaykus, L A

    2000-12-01

    Although viral foodborne disease is a significant problem, foods are rarely tested for viral contamination, and when done, testing is limited to shellfish commodities. In this work, we report a method to extract and detect human enteric viruses from alternative food commodities using an elution-concentration approach followed by detection using reverse transcription-polymerase chain reaction (RT-PCR). Fifty-gram lettuce or hamburger samples were artificially inoculated with poliovirus type 1 (PV1), hepatitis A virus (HAV), or the Norwalk virus and processed by the sequential steps of homogenization, filtration, Freon extraction (hamburger), and polyethylene glycol (PEG) precipitation. To reduce volumes further and remove RT-PCR inhibitors, a secondary PEG precipitation was necessary, resulting in an overall 10- to 20-fold sample size reduction from 50 g to 3 to 5 ml. Virus recoveries in secondary PEG concentrates ranged from 10 to 70% for PV1 and 2 to 4% for HAV as evaluated by mammalian cell culture infectivity assay. Total RNA from PEG concentrates was extracted to a small volume (30 to 40 microl) and subjected to RT-PCR amplification of viral RNA sequences. Detection limit studies indicated that viral RNA was consistently detected by RT-PCR at initial inoculum levels > or =102 PFU/50-g food sample for PV1 and > or =10(3) PFU/50-g food sample for HAV. In similar studies with the Norwalk virus, detection at inoculum levels > or =1.5 X 10(3) PCR-amplifiable units/50-g sample for both food products was possible. All RT-PCR amplicons were confirmed by subsequent Southern hybridization. The procedure reported represents progress toward the development of methods to detect human enteric viral contamination in foods other than shellfish.

  13. Expression of human beta-defensins-1-4 in thyroid cancer cells and new insight on biologic activity of hBD-2 in vitro.

    Zhuravel, O V; Gerashchenko, O L; Khetsuriani, M R; Soldatkina, M A; Pogrebnoy, P V

    2014-09-01

    The study was aimed on analysis of human beta-defensin-1-4 (hBDs) mRNA expression in cultured thyroid cancer cells and evaluation of effects of recombinant hBD-2 (rec-hBD-2) on growth patterns, migration properties and expression of E-cadherin and vimentin in these cells. The study was performed on cultured follicular thyroid cancer WRO cells, papillary thyroid cancer TPC1 cells, and anaplastic thyroid cancer KTC-2 cells. For analysis of hBD-1-4 mRNA expression in thyroid cancer cells, semiquantitative RT-PCR was used. Effects of rec-hBD-2 on cell proliferation, viability, and migration were analyzed using direct cell counting, MTT test, and scratch assay respectively. Expression of vimentin and E-cadherin was evaluated by quantitative PCR (qPCR). By the data of RT-PCR, all three studied thyroid cancer cell lines express hBD-1 and -4 mRNA, but not hBD-2 mRNA, while hBD-3 expression was detected in WRO and KTC-2 cells. The treatment of TPC-1, WRO, and KTC-2 cells with 100-1000 nM rec-hBD-2 resulted in significant concentration-dependent suppression of cell proliferation, viability, and migratory property. By the data of qPCR, significant up-regulation of vimentin expression was registered in KTC-2 and WRO cells treated with 500 nM rec-hBD-2. Significant down-regulation of E-cadherin expression (p cells treated with the defensin. Also, it has been shown that TPC-1 cells treated with 500 nM rec-hBD-2 acquired more elongated morphology. The data demonstrate that hBD-2 in concentrations higher than 100 nM exerts significant concentration-dependent suppression of thyroid cancer cell growth and migration, and affects vimentin and E-cadherin expression dependent on histologic type of thyroid cancer cells.

  14. A subchronic feeding safety evaluation of transgenic milk containing human β-defensin 3 on reproductive system of C57BL/6J mouse.

    Gao, Ming-Qing; Zhang, Ruiqi; Yang, Yange; Luo, Yuru; Jiang, Ming; Zhang, Yingli; Zhang, Yong; Qing, Suzhu

    2018-05-01

    Bovine mastitis is an infectious disease of the mammary gland which has been generally treated by antibiotic delivery. While the increasing drug-resistant bacteria and the high consumption of the antibiotic had become a noticeable concern. In a previous study, a mammary special vector expressing human β-defensin 3 (hBD3) was transfected into bovine fetal fibroblasts to produce mastitis-resistant bovine. This investigation focused on potential unintended effects of transgenic milk containing hBD3 produced by these mastitis-resistant bovine on the reproductive system of C57BL/6J mice. Mice were fed with diets containing transgenic milk or conventional milk, nutritionally balanced to an AIN93G diet for 90 days, and non-milk diet was selected as the negative group. The reproductive system was given special attention including reproductive organ/body ratios, necropsy and histopathology, serum sex hormone, sperm parameters, estrus cycle and the expression level of some specific genes which could indicate the development and function of reproductive system. No diet-related significant differences were observed among three groups in this 90-day feeding study. The results indicated that hBD3 milk does not appear to exert any effect on the reproductive system in C57BL/6J rats compared with conventional milk or the control diet. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Transplantation of periodontal ligament cell sheets expressing human β-defensin-3 promotes anti-inflammation in a canine model of periodontitis

    Zhu, Minwen; Miao, Bo; Zhu, Jianhua; Wang, Haiyan; Zhou, Zengtong

    2017-01-01

    Periodontitis is a chronic oral inflammatory disease caused by microorganisms. Human β-defensin-3 (HBD-3) is an endogenous antimicrobial peptide that inhibits a broad spectrum of microorganisms. Cell sheet technology has been widely applied in tissue and organ reconstructions. In the current study, it was aimed to investigate the anti-inflammatory effect of periodontal tissue engineered by HBD-3 gene-modified periodontal ligament cell (PDLC) sheets, and to identify a suitable method of promoting the regeneration of periodontal tissues. Western blot analysis and antimicrobial tests were used to confirm the expression of HBD-3. The effect of the cell sheets on anti-inflammatory activity and bone remodeling in a dog model of periodontitis was demonstrated by immunohistochemistry. The results demonstrated that the transfected PDLCs stably expressed HBD-3. Periodontal pathogens were susceptible to the antimicrobial activity of the cell sheets. In addition, the cell sheets relieved the bone resorption caused by inflammation in the in vivo model. HBD-3 may potentially be applied in the treatment of periodontitis and may function as osteogenic promoter via its anti-inflammatory effect. PMID:28944821

  16. The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants.

    Ahn, Ki Bum; Kim, A Reum; Kum, Kee-Yeon; Yun, Cheol-Heui; Han, Seung Hyun

    2017-10-01

    Streptococcus mutans is a major etiologic agent of human dental caries that forms biofilms on hard tissues in the human oral cavity, such as tooth and dentinal surfaces. Human β-defensin-3 (HBD3) is a 45-amino-acid natural antimicrobial peptide that has broad spectrum antimicrobial activity against bacteria and fungi. A synthetic peptide consisting of the C-terminal 15 amino acids of HBD3 (HBD3-C15) was recently shown to be sufficient for its antimicrobial activity. Thus, clinical applications of this peptide have garnered attention. In this study, we investigated whether HBD3-C15 inhibits the growth of the representative cariogenic pathogen Streptococcus mutans and its biofilm formation. HBD3-C15 inhibited bacterial growth, exhibited bactericidal activity, and attenuated bacterial biofilm formation in a dose-dependent manner. HBD3-C15 potentiated the bactericidal and anti-biofilm activity of calcium hydroxide (CH) and chlorhexidine digluconate (CHX), which are representative disinfectants used in dental clinics, against S. mutans. Moreover, HBD3-C15 showed antimicrobial activity by inhibiting biofilm formation by S. mutans and other dentinophilic bacteria such as Enterococcus faecalis and Streptococcus gordonii, which are associated with dental caries and endodontic infection, on human dentin slices. These effects were observed for HBD3-C15 alone and for HBD3-C15 in combination with CH or CHX. Therefore, we suggest that HBD3-C15 is a potential alternative or additive disinfectant that can be used for the treatment of oral infectious diseases, including dental caries and endodontic infections.

  17. Human β-defensin 3-combined gold nanoparticles for enhancement of osteogenic differentiation of human periodontal ligament cells in inflammatory microenvironments

    Zhou J

    2018-01-01

    Full Text Available Jing Zhou,1 Yangheng Zhang,1 Lingjun Li,1 Huangmei Fu,2 Wenrong Yang,2 Fuhua Yan1 1Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia Objective: It is a great challenge to absorb and conduct biophysicochemical interactions at the nano-bio interface. Peptides are emerging as versatile materials whose function can be programmed to perform specific tasks. Peptides combined nanoparticles might be utilized as a new approach of treatment. Human β-defensin 3 (hBD3, possesses both antimicrobial and proregeneration properties. Gold nanoparticles (AuNPs have shown promising applications in the field of tissue engineering. However, the coordinating effects of AuNPs and hBD3 on human periodontal ligament cells (hPDLCs remain unknown. In this study, we systematically investigated whether AuNPs and hBD3 would be able to coordinate and enhance the osteogenic differentiation of hPDLCs in inflammatory microenvironments, and the underlying mechanisms was explored. Methods: hPDLCs were stimulated with E. coli-LPS, hBD3 and AuNPs. Alkaline phosphatase (ALP and alizarin red S staining were used to observe the effects of hBD3 and AuNPs on the osteogenic differentiation of hPDLCs. Real-time PCR and western blot were performed to evaluate the osteogenic differentiation and Wnt/β-catenin signaling pathway related gene and protein expression.Results: In the inflammatory microenvironments stimulated by E. coli-LPS, we found that AuNPs and hBD3 increased the proliferation of hPDLCs slightly. In addition, hBD3-combined AuNPs could significantly enhance ALP activities and mineral deposition in vitro. Meanwhile, we observed that the osteogenic differentiation-related gene and protein expressions of ALP, collagenase-I (COL-1 and runt-related transcription factor 2 (Runx-2 were

  18. Defensins: antifungal lessons from eukaryotes

    Patrícia M. Silva

    2014-03-01

    Full Text Available Over the last years, antimicrobial peptides (AMPs have been the focus of intense research towards the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantæ and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components are presented. Additionally, recent works on antifungal defensins structure, activity and citotoxicity are also reviewed.

  19. Identification, cloning and functional characterization of novel beta-defensins in the rat (Rattus norvegicus

    French Frank S

    2006-02-01

    Full Text Available Abstract Background beta-defensins are small cationic peptides that exhibit broad spectrum antimicrobial properties. The majority of beta-defensins identified in humans are predominantly expressed in the male reproductive tract and have roles in non-immunological processes such as sperm maturation and capacitation. Characterization of novel defensins in the male reproductive tract can lead to increased understanding of their dual roles in immunity and sperm maturation. Methods In silico rat genomic analyses were used to identify novel beta-defensins related to human defensins 118–123. RNAs isolated from male reproductive tract tissues of rat were reverse transcribed and PCR amplified using gene specific primers for defensins. PCR products were sequenced to confirm their identity. RT-PCR analysis was performed to analyze the tissue distribution, developmental expression and androgen regulation of these defensins. Recombinant defensins were tested against E. coli in a colony forming unit assay to analyze their antimicrobial activities. Results Novel beta-defensins, Defb21, Defb24, Defb27, Defb30 and Defb36 were identified in the rat male reproductive tract. Defb30 and Defb36 were the most restricted in expression, whereas the others were expressed in a variety of tissues including the female reproductive tract. Early onset of defensin expression was observed in the epididymides of 10–60 day old rats. Defb21-Defb36 expression in castrated rats was down regulated and maintained at normal levels in testosterone supplemented animals. DEFB24 and DEFB30 proteins showed potent dose and time dependent antibacterial activity. Conclusion Rat Defb21, Defb24, Defb27, Defb30 and Defb36 are abundantly expressed in the male reproductive tract where they most likely protect against microbial invasion. They are developmentally regulated and androgen is required for full expression in the adult epididymis.

  20. CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection

    Fernández, Andrea G.; Bonetto, Josefina; Giambartolomei, Guillermo H.; Fossati, Carlos A.; Baldi, Pablo C.

    2015-01-01

    Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas Brucella spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that B. abortus induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human monocytes, monocyte-derived macrophages and the monocytic cell line THP-1. CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed B. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide (LPS). Accordingly, CCL20 production by B. abortus-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it was significantly induced in A549 cells by conditioned media from B. abortus-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD) 50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the B. abortus strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site. PMID:26448160

  1. Human enteric pathogen internalization by root uptake into food crops

    With an increasing number of outbreaks and illnesses associated with pre-harvest contaminated produce, understanding the potential and mechanisms of produce contamination by enteric pathogens can aid in the development of preventative measures and post-harvest processing to reduce microbial populati...

  2. Round-robin comparison of methods for the detection of human enteric viruses in lettuce

    Le Guyader, Francoise S.; Schultz, Anna Charlotte; Haugarreau, Larissa

    2004-01-01

    Five methods that detect human enteric virus contamination in lettuce were compared. To mimic multiple contaminations as observed after sewage contamination, artificial contamination was with human calicivirus and poliovirus and animal calicivirus strains at different concentrations. Nucleic acid...

  3. The defensin from avocado (Persea americana var. drymifolia) PaDef induces apoptosis in the human breast cancer cell line MCF-7.

    Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo; Salgado-Garciglia, Rafael; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

    2016-08-01

    Antimicrobial peptides (AMPs) are cytotoxic to cancer cells; however, mainly the effects of AMPs from animals have been evaluated. In this work, we assessed the cytotoxicity of PaDef defensin from avocado (Persea americana var. drymifolia) on the MCF-7 cancer cell line (a breast cancer cell line) and evaluated its mechanism of action. PaDef inhibited the viability of MCF-7 cells in a concentration-dependent manner, with an IC50=141.62μg/ml. The viability of normal peripheral blood mononuclear cells was unaffected by this AMP. Additionally, PaDef induced apoptosis in MCF-7 cells in a time-dependent manner, but did not affect the membrane potential or calcium flow. In addition, PaDef IC50 induced the expression of cytochrome c, Apaf-1, and the caspase 7 and 9 genes. Likewise, this defensin induced the loss of mitochondrial Δψm and increased the phosphorylation of MAPK p38, which may lead to MCF-7 apoptosis by the intrinsic pathway. This is the first report of an avocado defensin inducing intrinsic apoptosis in cancer cells, which suggests that it could be a potential therapeutic molecule in the treatment of cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

    Burgess Juliana

    2005-12-01

    Full Text Available Abstract Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2 is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF, and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.

  5. Anti-Bacterial Activity of Recombinant Human β-Defensin-3 Secreted in the Milk of Transgenic Goats Produced by Somatic Cell Nuclear Transfer

    Han, Chengquan; Zhang, Hui; Wang, Yongsheng; Su, Jianmin; Quan, Fusheng; Gao, Mingqing; Zhang, Yong

    2013-01-01

    The present study was conducted to determine whether recombinant human β-defensin-3 (rHBD3) in the milk of transgenic goats has an anti-bacterial activity against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Streptococcus agalactiae (S. agalactiae) that could cause mastitis. A HBD3 mammary-specific expression vector was transfected by electroporation into goat fetal fibroblasts which were used to produce fourteen healthy transgenic goats by somatic cell nuclear transfer. The expression level of rHBD3 in the milk of the six transgenic goats ranged from 98 to 121 µg/ml at 15 days of lactation, and was maintained at 90–111 µg/ml during the following 2 months. Milk samples from transgenic goats showed an obvious inhibitory activity against E. coli, S. aureus and S. agalactiae in vitro. The minimal inhibitory concentrations of rHBD3 in milk against E. coli, S. aureus and S. agalactiae were 9.5–10.5, 21.8–23.0 and 17.3–18.5 µg/mL, respectively, which was similar to those of the HBD3 standard (P>0.05). The in vivo anti-bacterial activities of rHBD3 in milk were examined by intramammary infusion of viable bacterial inoculums. We observed that 9/10 and 8/10 glands of non-transgenic goats infused with S. aureus and E. coli became infected. The mean numbers of viable bacteria went up to 2.9×103 and 95.4×103 CFU/ml at 48 h after infusion, respectively; the mean somatic cell counts (SCC) in infected glands reached up to 260.4×105 and 622.2×105 cells/ml, which were significantly higher than the SCC in uninfected goat glands. In contrast, no bacteria was presented in glands of transgenic goats and PBS-infused controls, and the SSC did not significantly change throughout the period. Moreover, the compositions and protein profiles of milk from transgenic and non-transgenic goats were identical. The present study demonstrated that HBD3 were an effective anti-bacterial protein to enhance the mastitis resistance of dairy animals. PMID:23799010

  6. Human milk consumption and full enteral feeding among infants who weigh

    Sisk, Paula M; Lovelady, Cheryl A; Gruber, Kenneth J; Dillard, Robert G; O'Shea, T Michael

    2008-06-01

    Establishing enteral feeding is an important goal in the care of very low birth weight infants. In such infants, receipt of >/=50 mL/kg per day human milk during hospitalization has been associated with shorter time to full enteral feeding. The objective of this study was to determine whether high proportions (>/=50%) of human milk during feeding advancement are associated with shorter time to full enteral feeding and improved feeding tolerance. This was a prospective cohort study of very low birth weight infants (n = 127) who were grouped into low (/=50%; n = 93) human milk consumption groups according to their human milk proportion of enteral feeding during the time of feeding advancement. The primary outcomes of interest were ages at which 100 and 150 mL/kg per day enteral feedings were achieved. The high human milk group reached 100 mL/kg per day enteral feeding 4.5 days faster than the low human milk group. The high human milk group reached 150 mL/kg per day enteral feeding 5 days faster than the low human milk group. After adjustment for gestational age, gender, and respiratory distress syndrome, times to reach 100 and 150 mL/kg per day were significantly shorter for those in the high human milk group. Infants in the high human milk group had a greater number of stools per day; other indicators of feeding tolerance were not statistically different. In infants who weighed milk was associated with fewer days to full enteral feedings.

  7. The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes.

    Funderburg, Nicholas T; Jadlowsky, Julie K; Lederman, Michael M; Feng, Zhimin; Weinberg, Aaron; Sieg, Scott F

    2011-10-01

    Human β-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3) CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1β, but only Pam(3) CSK(4) induced IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen-activated protein kinases were activated similarly by hBD-3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-κB pathway was only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical nuclear factor-κB signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  8. Characterization of the antimicrobial peptide family defensins in the Tasmanian devil (Sarcophilus harrisii), koala (Phascolarctos cinereus), and tammar wallaby (Macropus eugenii).

    Jones, Elizabeth A; Cheng, Yuanyuan; O'Meally, Denis; Belov, Katherine

    2017-03-01

    Defensins comprise a family of cysteine-rich antimicrobial peptides with important roles in innate and adaptive immune defense in vertebrates. We characterized alpha and beta defensin genes in three Australian marsupials: the Tasmanian devil (Sarcophilus harrisii), koala (Phascolarctos cinereus), and tammar wallaby (Macropus eugenii) and identified 48, 34, and 39 defensins, respectively. One hundred and twelve have the classical antimicrobial peptides characteristics required for pathogen membrane targeting, including cationic charge (between 1+ and 15+) and a high proportion of hydrophobic residues (>30%). Phylogenetic analysis shows that gene duplication has driven unique and species-specific expansions of devil, koala, and tammar wallaby beta defensins and devil alpha defensins. Defensin genes are arranged in three genomic clusters in marsupials, whereas further duplications and translocations have occurred in eutherians resulting in four and five gene clusters in mice and humans, respectively. Marsupial defensins are generally under purifying selection, particularly residues essential for defensin structural stability. Certain hydrophobic or positively charged sites, predominantly found in the defensin loop, are positively selected, which may have functional significance in defensin-target interaction and membrane insertion.

  9. The Fungal Defensin Family Enlarged

    Jiajia Wu

    2014-08-01

    Full Text Available Fungi are an emerging source of peptide antibiotics. With the availability of a large number of model fungal genome sequences, we can expect that more and more fungal defensin-like peptides (fDLPs will be discovered by sequence similarity search. Here, we report a total of 69 new fDLPs encoded by 63 genes, in which a group of fDLPs derived from dermatophytes are defined as a new family (fDEF8 according to sequence and phylogenetic analyses. In the oleaginous fungus Mortierella alpine, fDLPs have undergone extensive gene expansion. Our work further enlarges the fungal defensin family and will help characterize new peptide antibiotics with therapeutic potential.

  10. Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.

    Westerberg, Sonja; Hagbom, Marie; Rajan, Anandi; Loitto, Vesa; Persson, B David; Allard, Annika; Nordgren, Johan; Sharma, Sumit; Magnusson, Karl-Eric; Arnberg, Niklas; Svensson, Lennart

    2018-04-01

    Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41

  11. Distinct signaling pathways leading to the induction of human β-defensin 2 by stimulating an electrolyticaly-generated acid functional water and double strand RNA in oral epithelial cells.

    Gojoubori, Takahiro; Nishio, Yukina; Asano, Masatake; Nishida, Tetsuya; Komiyama, Kazuo; Ito, Koichi

    2014-04-01

    Defensins, a major family of cationic antimicrobial peptides, play important roles in innate immunity. In the present study, we investigated whether double-stranded RNA (dsRNA), a by-product of RNA virus replication, can induce human β-defensins-2 (hBD-2) expression in oral epithelial cells (OECs). We also examined the hBD-2-inducible activity of acid-electrolyzed functional water (FW). The results indicated that both dsRNA- and FW-induced hBD-2 expression in OECs. The induction efficiency was much higher for FW than for dsRNA. FW-induced production of hBD-2 was clearly observed by immunofluorescence staining. A luciferase assay was performed with 1.2 kb of the 5'-untranslated region (5'-UTR) of the hBD-2 gene. The results indicated that the nuclear factor-kappa B (NF-κB)-binding site proximal to the translation initiation site was indispensable for dsRNA-stimulated hBD-2 expression, but not in the case of FW. Moreover, FW-stimulated hBD-2 expression did not depend on NF-κB activity; instead, FW inhibited NF-κB activity. Pretreatment of the cells with specific inhibitors against NF-κB further confirmed NF-κB-independent hBD-2 induction by FW. In analogy to the results for intestinal epithelial cells (IECs), the dsRNA signal, but not FW, was sensed by toll-like receptor 3 (TLR3) in OECs. These results suggested that hBD-2 expression induced by dsRNA and FW is regulated by distinct mechanisms in OECs.

  12. Evaluation of Human Enteric Viruses in Surface Water and Drinking Water Resources in Southern Ghana

    Gibson, Kristen E.; Opryszko, Melissa C.; Schissler, James T.; Guo, Yayi; Schwab, Kellogg J.

    2011-01-01

    An estimated 884 million people worldwide do not have access to an improved drinking water source, and the microbial quality of these sources is often unknown. In this study, a combined tangential flow, hollow fiber ultrafiltration (UF), and real-time PCR method was applied to large volume (100 L) groundwater (N = 4), surface water (N = 9), and finished (i.e., receiving treatment) drinking water (N = 6) samples for the evaluation of human enteric viruses and bacterial indicators. Human enteric viruses including norovirus GI and GII, adenovirus, and polyomavirus were detected in five different samples including one groundwater, three surface water, and one drinking water sample. Total coliforms and Escherichia coli assessed for each sample before and after UF revealed a lack of correlation between bacterial indicators and the presence of human enteric viruses. PMID:21212196

  13. A crucial role of paralogous β-defensin genes in the Chinese alligator innate immune system revealed by the first determination of a Crocodilia defensin cluster.

    Tang, Ke-Yi; Wang, Xin; Wan, Qiu-Hong; Fang, Sheng-Guo

    2018-04-01

    The β-defensin, one of the antimicrobial peptides (AMPs), is a significant component of the innate immune with a broad range of antimicrobial activities. Differing from the widely-studied mammals and birds, limited information about β-defensins has been reported in reptiles, especially in crocodilians. As a same ancient species as dinosaurs and the most endangered species of 23 crocodilians, the survival of Chinese alligator (Alligator sinensis) means a powerful immune system and possible involvement of AMPs in its immune resistance. In this study, we identified 20 novel Alligator sinensisβ-defensin genes (AsBDs) from a 390 kb region using bioinformatic and experimental approaches, and successfully distinguished six orthologous AsBDs to birds and nine paralogous AsBDs undergoing gene duplication events. The amino acid alignment shows that the AsBD paralogs, like α-defensins, encode a significantly longer pro-piece comparing with the orthologs. The calculation of non-synonymous (d N ) and synonymous (d S ) substitutions in the mature peptide reveals that the AsBD paralogs experience a significantly higher selective pressure (d N /d S ) than the orthologs, but a similar evolutionary force to α-defensins. The gene expression result indicates that the AsBD paralogs have a significantly higher expression level than the orthologos in gastrointestinal tract where the host is vulnerable to enteric pathogenic bacteria, as observed in α-defensins. These three pieces of evidence demonstrate that the AsBD paralogs do play an important role in maintaining long-term survival of this endangered reptile. Thus, this survey of AsBDs on the genomic structure, evolutionary characteristics, and expression pattern provides a genetic and immunological foundation for further investigating their antimicrobial function and alternative antibiotics potentiality. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Recent advances in regenerative medicine to treat enteric neuropathies: use of human cells.

    Stamp, L A; Young, H M

    2017-01-01

    As current options for treating most enteric neuropathies are either non-effective or associated with significant ongoing problems, cell therapy is a potential attractive possibility to treat congenital and acquired neuropathies. Studies using animal models have shown that following transplantation of enteric neural progenitors into the bowel of recipients, the transplanted cells migrate, proliferate, and generate neurons that are electrically active and receive synaptic inputs. Recent studies have transplanted human enteric neural progenitors into the mouse colon and shown engraftment. In this article, we summarize the significance of these recent advances and discuss priorities for future research that might lead to the use of regenerative medicine to treat enteric neuropathies in the clinic. © 2016 John Wiley & Sons Ltd.

  15. Expression of natural antimicrobial peptide β-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers

    Urszula Wojewodzka

    2011-08-01

    Full Text Available Chronic wounds like venous calf and diabetic foot ulcers are frequently contaminated and colonized by bacteria and it remains unclear whether there is sufficient expression of defensins and recruitment of epidermal Langerhans cells in the margin of ulcer compared to normal skin. The aim of this study was to examine immunohistochemically the expression of β-defensin-2 (hBD2, GM-CSF, VEGF growth factors and accumulation of CD1a+ Langerhans cells (LC in epidermis from chronic skin ulcers and to compare it to normal skin from the corresponding areas. Studies were carried out in 10 patients with diabetic foot, 10 patients with varicous ulcers of the calf and 10 patients undergoing orthopedic surgery (normal skin for control. Biopsy specimens were immunostained using specific primary antibodies, LSAB+ kit based on biotin-avidinperoxidase complex technique and DAB chromogen. Results were expressed as a mean staining intensity. Statistical analysis of staining showed significantly higher staining of hBD2 in both normal and ulcerated epidermis from foot sole skin compared to calf skin (normal and ulcerated, p<0.05. Chronic ulcers showed the same expression of hBD2 as normal skin. There was significantly lower accumulation of CD1a+ LC in normal epidermis from foot sole skin compared to normal calf skin (p<0.05. Accumulation of CD1a+ LC and GM-CSF upregulation at the border area of diabetic foot ulcer and reduction of LC concentration at the margin of venous calf ulcer compared to normal skin were observed. It seems that normal calf and sole epidermis is, unlike in the mechanisms of innate immunity, influenced by the different keratinocyte turnover and bacterial flora colonizing these regions. Insufficient upregulation of hBD2 in both diabetic foot and venous calf ulcers may suggest the pathological role of this protein in the chronicity of ulcers.

  16. Groundwater sampling methods using glass wool filtration to trace human enteric viruses in Madison, Wisconsin

    Human enteric viruses have been detected in the Madison, Wisconsin deep municipal well system. Earlier projects by the Wisconsin Geological and Natural History Survey (WGNHS) have used glass wool filters to sample groundwater for these viruses directly from the deep municipal wells. Polymerase chain...

  17. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

    Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

    2010-01-01

    Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1 - low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2 - the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3 - knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

  18. Accelerated modern human?induced species losses: Entering the sixth mass extinction

    Ceballos, Gerardo; Ehrlich, Paul R.; Barnosky, Anthony D.; Garc?a, Andr?s; Pringle, Robert M.; Palmer, Todd M.

    2015-01-01

    The oft-repeated claim that Earth?s biota is entering a sixth ?mass extinction? depends on clearly demonstrating that current extinction rates are far above the ?background? rates prevailing between the five previous mass extinctions. Earlier estimates of extinction rates have been criticized for using assumptions that might overestimate the severity of the extinction crisis. We assess, using extremely conservative assumptions, whether human activities are causing a mass extinction. First, we...

  19. Rabbit defensin (NP-1) genetic engineering of plant | Ting | African ...

    Rabbit defensin (NP-1) genetic engineering of plant. ... Log in or Register to get access to full text downloads. ... defensin genetic engineering of plant in recent years, and also focuses on the existing problems and new strategies in this area.

  20. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

    Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

    2017-01-01

    Understanding host?enteric virus interactions has been limited by the inability to culture nontransformed small intestinal epithelial cells and to infect animal models with human viruses. We report epithelial responses in human small intestinal enteroid cultures from different individuals following infection with human rotavirus (HRV), a model enteric pathogen. RNA-sequencing and functional assays revealed type III IFN as the dominant transcriptional response that activates interferon-stimula...

  1. Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to Substance P, Hemokinin-1, Human β-Defensin-3, and Icatibant.

    Alkanfari, Ibrahim; Gupta, Kshitij; Jahan, Tahsin; Ali, Hydar

    2018-05-23

    Human mast cells (MCs) express a novel G protein-coupled receptor (GPCR) known as Mas-related GPCR X2 (MRGPRX2). Activation of this receptor by a diverse group of cationic ligands such as neuropeptides, host defense peptides, and Food and Drug Administration-approved drugs contributes to chronic inflammatory diseases and pseudoallergic drug reactions. For most GPCRs, the extracellular (ECL) domains and their associated transmembrane (TM) domains display the greatest structural diversity and are responsible for binding different ligands. The goal of the current study was to determine if naturally occurring missense variants within MRGPRX2's ECL/TM domains contribute to gain or loss of function phenotype for MC degranulation in response to neuropeptides (substance P and hemokinin-1), a host defense peptide (human β-defensin-3) and a Food and Drug Administration-approved cationic drug (bradykinin B2 receptor antagonist, icatibant). We have identified eight missense variants within MRGPRX2's ECL/TM domains from publicly available exome-sequencing databases. We investigated the ability of MRGPRX2 ligands to induce degranulation in rat basophilic leukemia-2H3 cells individually expressing these naturally occurring MRGPRX2 missense variants. Using stable and transient transfections, we found that all variants express in rat basophilic leukemia cells. However, four natural MRGPRX2 variants, G165E (rs141744602), D184H (rs372988289), W243R (rs150365137), and H259Y (rs140862085) failed to respond to any of the ligands tested. Thus, diverse MRGPRX2 ligands use common sites on the receptor to induce MC degranulation. These findings have important clinical implications for MRGPRX2 and MC-mediated pseudoallergy and chronic inflammatory diseases. Copyright © 2018 by The American Association of Immunologists, Inc.

  2. ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria

    Joanna Baricelli

    2015-02-01

    Full Text Available OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA. Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n = 61 than in mature milk samples (n = 39, as follows: median and range, 8.52 (2.6-16.3 µg/ml versus 0.97 (0.22-3.78, p < 0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients.

  3. Sampling methods for recovery of human enteric viruses from environmental surfaces.

    Turnage, Nicole L; Gibson, Kristen E

    2017-10-01

    Acute gastroenteritis causes the second highest infectious disease burden worldwide. Human enteric viruses have been identified as leading causative agents of acute gastroenteritis as well as foodborne illnesses in the U.S. and are generally transmitted by fecal-oral contamination. There is growing evidence of transmission occurring via contaminated fomite including food contact surfaces. Additionally, human enteric viruses have been shown to remain infectious on fomites over prolonged periods of time. To better understand viral persistence, there is a need for more studies to investigate this phenomenon. Therefore, optimization of surface sampling methods is essential to aid in understanding environmental contamination to ensure proper preventative measures are being applied. In general, surface sampling studies are limited and highly variable among recovery efficiencies and research parameters used (e.g., virus type/density, surface type, elution buffers, tools). This review aims to discuss the various factors impacting surface sampling of viruses from fomites and to explore how researchers could move towards a more sensitive and standard sampling method. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Gold Nanoparticles: An Efficient Antimicrobial Agent against Enteric Bacterial Human Pathogen

    Shahzadi Shamaila

    2016-04-01

    Full Text Available Enteric bacterial human pathogens, i.e., Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Klebsiella pneumoniae, are the major cause of diarrheal infections in children and adults. Their structure badly affects the human immune system. It is important to explore new antibacterial agents instead of antibiotics for treatment. This project is an attempt to explain how gold nanoparticles affect these bacteria. We investigated the important role of the mean particle size, and the inhibition of a bacterium is dose-dependent. Ultra Violet (UV-visible spectroscopy revealed the size of chemically synthesized gold nanoparticle as 6–40 nm. Atomic force microscopy (AFM analysis confirmed the size and X-ray diffractometry (XRD analysis determined the polycrystalline nature of gold nanoparticles. The present findings explained how gold nanoparticles lyse Gram-negative and Gram-positive bacteria.

  5. Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

    Bai, Xiaoxia; Tian, Ting; Wang, Peng; Yang, Xiaofu; Wang, Zhengping; Dong, Minyue

    2015-03-01

    Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV. © 2014 Wiley Periodicals, Inc.

  6. Antifungal defensins and their role in plant defense.

    Lacerda, Ariane F; Vasconcelos, Erico A R; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term "plant defensin," after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins.

  7. Antifungal defensins and their role in plant defense

    Ariane eLacerda

    2014-04-01

    Full Text Available Since the beginning of the 90’s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP have been studied. However, Broekaert only coined the term plant defensin in 1995, after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity towards microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM. Its low effective concentration towards fungi, ranging from 0.1 to 10 µM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90’s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i the most studied plant defensins and their fungal targets; (ii the molecular features of plant defensins and their relation with antifungal activity; (iii the possibility of using plant defensin(s genes to generate fungi resistant GM crops and biofungicides; and (iv a brief discussion about the absence of products in the market containing plant antifungal defensins.

  8. Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

    Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

    2017-12-05

    Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

  9. Human enteric bacteria and viruses in five wastewater treatment plants in the Eastern Cape, South Africa

    Olayinka Osuolale

    2017-09-01

    Full Text Available Monitoring effluents from wastewater treatment plants is important to preventing both environmental contamination and the spread of disease. We evaluated the occurrence of human enteric bacteria (faecal coliforms and Escherichia coli and viruses (rotavirus and enterovirus in the final effluents of five wastewater treatment plants (WWTPs in the Eastern Cape of South Africa. Human viruses were recovered from the effluent samples with the adsorption–elution method and detected with singleplex real-time RT–PCR assays. Rotavirus was detected in several effluents samples, but no enterovirus was detected. At WWTP-C, rotavirus titre up to 105 genome copies/L was observed and present in 41.7% of the samples. At WWTP-B, the virus was detected in 41.7% of samples, with viral titres up to 103 genome copies/L. The virus was detected once at WWTP-E, in 9% of the samples analysed. The viral titres at WWTP-A were below the detection limit in all 25% of the 1.25 L samples in which the virus was detected. Rotavirus was not observed at WWTP-D. Faecal coliform bacteria and E. coli were detected in all the WWTPs, but no correlation was established between the enteric bacteria and viruses studied. The occurrence of rotavirus in effluent samples discharged into surface waters highlights the importance of assessing viral contamination in the water sources used for domestic water use. Keywords: Rotavirus, Enterovirus, Wastewater, Eastern Cape, Effluent, Faecal coliforms and Escherichia coli

  10. Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

    Radka Gromnicova

    Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

  11. A Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureus.

    Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Conery, Annie L; Fuchs, Beth Burgwyn; Kim, Wooseong; Johnston, Tatiana; Vilcinskas, Andreas; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    The red flour beetle Tribolium castaneum is a common insect pest and has been established as a model beetle to study insect development and immunity. This study demonstrates that defensin 1 from T. castaneum displays in vitro and in vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) of defensin 1 against 11 reference and clinical staphylococcal isolates was between 16-64 μg/ml. The putative mode of action of the defensin peptide is disruption of the bacterial cell membrane. The antibacterial activity of defensin 1 was attenuated by salt concentrations of 1.56 mM and 25 mM for NaCl and CaCl2 respectively. Treatment of defensin 1 with the reducing agent dithiothreitol (DTT) at concentrations 1.56 to 3.13 mM abolished the antimicrobial activity of the peptide. In the presence of subinhibitory concentrations of antibiotics that also target the bacterial cell envelope such as telavancin and daptomycin, the MIC of the peptide was as low as 1 μg/ml. Moreover, when tested against an S. aureus strain that was defective in D-alanylation of the cell wall, the MIC of the peptide was 0.5 μg/ml. Defensin 1 exhibited no toxicity against human erythrocytes even at 400 μg/ml. The in vivo activity of the peptide was validated in a Caenorhabditis elegans-MRSA liquid infection assay. These results suggest that defensin 1 behaves similarly to other cationic AMPs in its mode of action against S. aureus and that the activity of the peptide can be enhanced in combination with other antibiotics with similar modes of action or with compounds that have the ability to decrease D-alanylation of the bacterial cell wall.

  12. A Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureus.

    Rajmohan Rajamuthiah

    Full Text Available The red flour beetle Tribolium castaneum is a common insect pest and has been established as a model beetle to study insect development and immunity. This study demonstrates that defensin 1 from T. castaneum displays in vitro and in vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. The minimum inhibitory concentration (MIC of defensin 1 against 11 reference and clinical staphylococcal isolates was between 16-64 μg/ml. The putative mode of action of the defensin peptide is disruption of the bacterial cell membrane. The antibacterial activity of defensin 1 was attenuated by salt concentrations of 1.56 mM and 25 mM for NaCl and CaCl2 respectively. Treatment of defensin 1 with the reducing agent dithiothreitol (DTT at concentrations 1.56 to 3.13 mM abolished the antimicrobial activity of the peptide. In the presence of subinhibitory concentrations of antibiotics that also target the bacterial cell envelope such as telavancin and daptomycin, the MIC of the peptide was as low as 1 μg/ml. Moreover, when tested against an S. aureus strain that was defective in D-alanylation of the cell wall, the MIC of the peptide was 0.5 μg/ml. Defensin 1 exhibited no toxicity against human erythrocytes even at 400 μg/ml. The in vivo activity of the peptide was validated in a Caenorhabditis elegans-MRSA liquid infection assay. These results suggest that defensin 1 behaves similarly to other cationic AMPs in its mode of action against S. aureus and that the activity of the peptide can be enhanced in combination with other antibiotics with similar modes of action or with compounds that have the ability to decrease D-alanylation of the bacterial cell wall.

  13. β-Defensin genomic copy number does not influence the age of onset in Huntington's Disease.

    Vittori, Angelica; Orth, Michael; Roos, Raymund A C; Outeiro, Tiago F; Giorgini, Flaviano; Hollox, Edward J

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

  14. Novel aspects of defensins' involvement in virus-induced autoimmunity in the central nervous system.

    Kazakos, Evangelos I; Kountouras, Jannis; Polyzos, Stergios A; Deretzi, Georgia

    2017-05-01

    Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes. Therefore, in this review we describe current contributions in this field and we propose novel hypotheses regarding the potential impact of defensin-related pathways on virus-driven autoimmune neurodegeneration. In this regard, we have previously proposed that abnormal expression of defensins by penetrating the blood-brain barrier (BBB) may contribute to the pathophysiology of Helicobacter pylori-related brain neurodegenerative disorders through variable modulations of innate and adaptive immune responses. We hereby propose that impaired expression of defensins by structural components of the BBB may impede glymphatic circulation and disrupt receptor signalling in pericytes that is essential for microvascular stability, thereby retaining blood-derived toxins and bystander activated T-cells in the brain and further impairing BBB integrity and hampering viral clearance. Autoreactive T-cell infiltrates in neuronaxonal lesions characteristic of chronic central nervous system diseases, such as multiple sclerosis, are directed against both, myelin and non-myelin, antigens the precise nature of which remains enigmatic. Inadequate expression of the autoimmune regulator (AIRE), a gene expressed in medullary thymic epithelial cells, induces the recruitment of defensin-specific T-cells. These cells may access the brain, thereby causing a decrease in defensin expression and subsequent down-regulation of CD91/LRP1-mediated clearance of amyloid-β that

  15. Human enteric viruses in groundwater indicate offshore transport of human sewage to coral reefs of the Upper Florida Keys

    Futch, J. Carrie; Griffin, Dale W.; Lipp, Erin K.

    2010-01-01

    To address the issue of human sewage reaching corals along the main reef of the Florida Keys, samples were collected from surface water, groundwater and coral [surface mucopolysaccharide layers (SML)] along a 10 km transect near Key Largo, FL. Samples were collected semi-annually between July 2003 and September 2005 and processed for faecal indicator bacteria (faecal coliform bacteria, enterococci and Clostridium perfringens) and human-specific enteric viruses (enterovirus RNA and adenovirus DNA) by (RT)-nested polymerase chain reaction. Faecal indicator bacteria concentrations were generally higher nearshore and in the coral SML. Enteric viruses were evenly distributed across the transect stations. Adenoviruses were detected in 37 of 75 samples collected (49.3%) whereas enteroviruses were only found in 8 of 75 samples (10.7%). Both viruses were detected twice as frequently in coral compared with surface water or groundwater. Offshore, viruses were most likely to be found in groundwater, especially during the wet summer season. These data suggest that polluted groundwater may be moving to the outer reef environment in the Florida Keys.

  16. Assessment and impact of microbial fecal pollution and human enteric pathogens in a coastal community.

    Lipp, E K; Farrah, S A; Rose, J B

    2001-04-01

    The goals of this study were to assess watersheds impacted by high densities of OSDS (onsite sewage disposal systems) for evidence of fecal contamination and evaluate the occurrence of human pathogens in coastal waters off west Florida. Eleven stations (representing six watersheds) were intensively sampled for microbial indicators of fecal pollution (fecal coliform bacteria, enterococci, Clostridium perfringens and coliphage) and the human enteric pathogens, Cryptosporidium, Giardia, and enteroviruses during the summer rainy season (May-September 1996). Levels of all indicators ranged between 4000 CFU/100 ml. Cryptosporidium and Giardia were detected infrequently (6.8% and 2.3% of samples tested positive, respectively). Conversely, infectious enteroviruses were detected at low levels in 5 of the 6 watersheds sampled. Using cluster analysis, sites were grouped into two categories, high and low risks, based on combined levels of indicators. These results suggest that stations of highest pollution risk were located within areas of high OSDS densities. Furthermore, data indicate a subsurface transport of contaminated water to surface waters. The high prevalence of enteroviruses throughout the study area suggests a chronic pollution problem and potential risk to recreational swimmers in and around Sarasota Bay.

  17. Biodetection of potential genotoxic pollutants entering the human food chain through ashes used in livestock diets.

    Sanchez-Vicente, Laura; Herraez, Elisa; Briz, Oscar; Nogales, Rogelio; Molina-Alcaide, Eduarda; Marin, Jose J G

    2016-08-15

    Ash derived from energy generation is used as a source of minerals in livestock feeds. The microbial biosensor recApr-Luc2 was built to detect genotoxic hazard in recycled ash. Escherichia coli SOS gene (recA, lexA, dinI and umuC) expression in response to cisplatin-induced DNA damage led to the selection of the recA promoter. The biosensor required functional RecA expression to respond to genotoxic heavy metals (Cr>Cd≈Pb), and polluted ash induced a strong recApr-Luc2 response. In human liver and intestinal cells, heavy metals induced acute toxicity (Cr>Cd>Pb) at concentrations sufficient to activate recApr-Luc2. Cytostatic effects, including genotoxicity, were cell- and metal-dependent, apart from Cr. In agreement with the recApr-Luc2 bioassay, Cr had the strongest effect in all cells. In conclusion, recApr-Luc2 could be useful for evaluating the genotoxic risk of pollutants present in ash that might be concentrated in animal products and, thus, entering the human food chain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Interaction of Defensins with Model Cell Membranes

    Sanders, Lori K.; Schmidt, Nathan W.; Yang, Lihua; Mishra, Abhijit; Gordon, Vernita D.; Selsted, Michael E.; Wong, Gerard C. L.

    2009-03-01

    Antimicrobial peptides (AMPs) comprise a key component of innate immunity for a wide range of multicellular organisms. For many AMPs, activity comes from their ability to selectively disrupt and lyse bacterial cell membranes. There are a number of proposed models for this action, but the detailed molecular mechanism of selective membrane permeation remains unclear. Theta defensins are circularized peptides with a high degree of selectivity. We investigate the interaction of model bacterial and eukaryotic cell membranes with theta defensins RTD-1, BTD-7, and compare them to protegrin PG-1, a prototypical AMP, using synchrotron small angle x-ray scattering (SAXS). The relationship between membrane composition and peptide induced changes in membrane curvature and topology is examined. By comparing the membrane phase behavior induced by these different peptides we will discuss the importance of amino acid composition and placement on membrane rearrangement.

  19. Differential Susceptibility of Bacteria to Mouse Paneth Cell a-Defensins under Anaerobic Conditions

    Jennifer R. Mastroianni

    2014-10-01

    Full Text Available Small intestinal Paneth cells secrete a-defensin peptides, termed cryptdins (Crps in mice, into the intestinal lumen, where they confer immunity to oral infections and define the composition of the ileal microbiota. In these studies, facultative bacteria maintained under aerobic or anaerobic conditions displayed differential sensitivities to mouse a-defensins under in vitro assay conditions. Regardless of oxygenation, Crps 2 and 3 had robust and similar bactericidal activities against S. typhimurium and S. flexneri, but Crp4 activity against S. flexneri was attenuated in the absence of oxygen. Anaerobic bacteria varied in their susceptibility to Crps 2-4, with Crp4 showing less activity than Crps 2 and 3 against Enterococcus faecalis, and Bacteroides fragilis in anaerobic assays, but Fusobacterium necrophorum was killed only by Crp4 and not by Crps 2 and 3. The influence of anaerobiosis in modulating Crp bactericidal activities in vitro suggests that a-defensin effects on the enteric microbiota may be subject to regulation by local oxygen tension.

  20. Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

    Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

    2016-09-01

    Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

  1. Prevalence of human pathogenic enteric viruses in bivalve molluscan shellfish and cultured shrimp in south west coast of India.

    Umesha, Kanasinakatte R; Bhavani, Naniah C; Venugopal, Moleyur N; Karunasagar, Indrani; Krohne, Georg; Karunasagar, Iddya

    2008-03-20

    The prevalence of human enteric viruses in bivalve molluscan shellfish and shrimp collected off the south west coast of India was studied to assess the extent of fecal pollution of coastal environment. Out of 194 samples analyzed, 37% of oyster, 46% of clam and 15% of shrimp samples were positive for enteroviruses (EV). Adenoviruses (ADV) were detected in 17% of oyster and 27% of clam samples. However, other enteric viruses such as noroviruses (NoV) and hepatitis A virus (HAV) were not detected in any of the samples. High prevalence of EV and ADV was noticed between May to December. Thirty four percent of oyster and 49% of clam samples showed fecal coliform values higher than the limit. MS-2 phage was detected in 57% of oyster and 73% of clam samples. The presence of MS-2 phage and human enteric viruses showed association while fecal coliforms and enteric viruses showed no association. However, 17 samples, which were positive for enteric viruses (EV and ADV), were negative for MS-2 phage.

  2. Partial characterization of three β-defensin gene transcripts in river ...

    In this study, the tracheal tissues from Egyptian river buffalo and cattle were screened for the presence of three bovine β-defensin gene transcripts. Three primer pairs were designed on the basis of published Bos taurus sequences for partial amplification of β-defensin 4, β-defensin 10 and β-defensin 11 complementary DNA ...

  3. The effect of cranberry juice and cranberry proanthocyanidins on the infectivity of human enteric viral surrogates.

    Su, Xiaowei; Howell, Amy B; D'Souza, Doris H

    2010-06-01

    The effect of cranberry juice (CJ) and cranberry proanthocyanidins (PAC) on the infectivity of human enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), MS2(ssRNA) bacteriophage, and phiX-174(ssDNA) bacteriophage was studied. Viruses at high (approximately 7 log(10) PFU/ml) or low (approximately 5 log(10) PFU/ml) titers were mixed with equal volumes of CJ, 0.30, 0.60, and 1.20 mg/ml final PAC concentration, or water and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. At low viral titers, FCV-F9 was undetectable after exposure to CJ or the three tested PAC solutions. MNV-1 was reduced by 2.06 log(10) PFU/ml with CJ, and 2.63, 2.75, and 2.95 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. MS2 titers were reduced by 1.14 log(10) PFU/ml with CJ, and 0.55, 0.80, and 0.96 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. phi-X174 titers were reduced by 1.79 log(10) PFU/ml with CJ, and 1.95, 3.67, and 4.98 log(10) PFU/ml with PAC at 0.15, 0.30, and 0.60 mg/ml, respectively. Experiments using high titers showed similar trends but with decreased effects. CJ and PAC show promise as natural antivirals that could potentially be exploited for foodborne viral illness treatment and prevention. 2010 Elsevier Ltd. All rights reserved.

  4. Accelerated modern human-induced species losses: Entering the sixth mass extinction.

    Ceballos, Gerardo; Ehrlich, Paul R; Barnosky, Anthony D; García, Andrés; Pringle, Robert M; Palmer, Todd M

    2015-06-01

    The oft-repeated claim that Earth's biota is entering a sixth "mass extinction" depends on clearly demonstrating that current extinction rates are far above the "background" rates prevailing between the five previous mass extinctions. Earlier estimates of extinction rates have been criticized for using assumptions that might overestimate the severity of the extinction crisis. We assess, using extremely conservative assumptions, whether human activities are causing a mass extinction. First, we use a recent estimate of a background rate of 2 mammal extinctions per 10,000 species per 100 years (that is, 2 E/MSY), which is twice as high as widely used previous estimates. We then compare this rate with the current rate of mammal and vertebrate extinctions. The latter is conservatively low because listing a species as extinct requires meeting stringent criteria. Even under our assumptions, which would tend to minimize evidence of an incipient mass extinction, the average rate of vertebrate species loss over the last century is up to 100 times higher than the background rate. Under the 2 E/MSY background rate, the number of species that have gone extinct in the last century would have taken, depending on the vertebrate taxon, between 800 and 10,000 years to disappear. These estimates reveal an exceptionally rapid loss of biodiversity over the last few centuries, indicating that a sixth mass extinction is already under way. Averting a dramatic decay of biodiversity and the subsequent loss of ecosystem services is still possible through intensified conservation efforts, but that window of opportunity is rapidly closing.

  5. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

    Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

    2017-01-01

    The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine. PMID:28069942

  6. Removal properties of human enteric viruses in a pilot-scale membrane bioreactor (MBR) process.

    Miura, Takayuki; Okabe, Satoshi; Nakahara, Yoshihito; Sano, Daisuke

    2015-05-15

    In order to evaluate removal properties of human enteric viruses from wastewater by a membrane bioreactor (MBR), influent, anoxic and oxic mixed liquor, and membrane effluent samples were collected in a pilot-scale anoxic-oxic MBR process for 16 months, and concentrations of enteroviruses, norovirus GII, and sapoviruses were determined by real-time PCR using murine norovirus as a process control. Mixed liquor samples were separated into liquid and solid phases by centrifugation, and viruses in the bulk solution and those associated with mixed liquor suspended solids (MLSS) were quantified. Enteroviruses, norovirus GII, and sapoviruses were detected in the influent throughout the sampling period (geometrical mean, 4.0, 3.1, and 4.4 log copies/mL, respectively). Enterovirus concentrations in the solid phase of mixed liquor were generally lower than those in the liquid phase, and the mean log reduction value between influent and anoxic mixed liquor was 0.40 log units. In contrast, norovirus GII and sapovirus concentrations in the solid phase were equal to or higher than those in the liquid phase, and higher log reduction values (1.3 and 1.1 log units, respectively) were observed between influent and anoxic mixed liquor. This suggested that enteroviruses were less associated with MLSS than norovirus GII and sapoviruses, resulting in lower enterovirus removal in the activated sludge process. Enteroviruses and norovirus GII were detected in the MBR effluent but sapoviruses were not in any effluent samples. When MLSS concentration was reduced to 50-60% of a normal operation level, passages of enteroviruses and norovirus GII through a PVDF microfiltration membrane were observed. Since rejection of viruses by the membrane was not related to trans-membrane pressure which was monitored as a parameter of membrane fouling, the results indicated that adsorption to MLSS plays an important role in virus removal by an MBR, and removal properties vary by viruses reflecting different

  7. The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets.

    Elahi, Shokrollah; Buchanan, Rachelle M; Attah-Poku, Sam; Townsend, Hugh G G; Babiuk, Lorne A; Gerdts, Volker

    2006-04-01

    Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 mug pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.

  8. Permeabilization of fungal hyphae by the plant defensin NaD1 occurs through a cell wall-dependent process.

    van der Weerden, Nicole L; Hancock, Robert E W; Anderson, Marilyn A

    2010-11-26

    The antifungal activity of the plant defensin NaD1 involves specific interaction with the fungal cell wall, followed by permeabilization of the plasma membrane and entry of NaD1 into the cytoplasm. Prior to this study, the role of membrane permeabilization in the activity of NaD1, as well as the relevance of cell wall binding, had not been investigated. To address this, the permeabilization of Fusarium oxysporum f. sp. vasinfectum hyphae by NaD1 was investigated and compared with that by other antimicrobial peptides, including the cecropin-melittin hybrid peptide CP-29, the bovine peptide BMAP-28, and the human peptide LL-37, which are believed to act largely through membrane disruption. NaD1 appeared to permeabilize cells via a novel mechanism that required the presence of the fungal cell wall. NaD1 and Bac2A, a linear variant of the bovine peptide bactenecin, were able to enter the cytoplasm of treated hyphae, indicating that cell death is accelerated by interaction with intracellular targets.

  9. Impacts of sanitation improvement on reduction of nitrogen discharges entering the environment from human excreta in China.

    Tong, Yindong; Bu, Xiaoge; Chen, Cen; Yang, Xi; Lu, Yiren; Liang, Huijiao; Liu, Maodian; Lin, Huiming; Zhang, Haoran; Lin, Yan; Zhou, Feng; Zhao, Shen; Wu, Tianyu; Mao, Guozhu; Zhang, Wei; Wang, Xuejun

    2017-09-01

    Identifying the sanitation efficacy in reducing contaminations entering the environment is an important step for water pollution controls and developing management strategies to further improve sanitation conditions. With continuous efforts in sanitation improvement during the past decade, reductions in discharges of aquatic nutrients are expected in China. In this study, we estimated the aquatic nitrogen discharges from human excreta in 31 provinces in China during 2006-2014. The results indicated that the nitrogen discharges entering the environment from human excreta are largely determined by both local population and sanitation conditions. In 2014, the nitrogen discharges from human excreta in the rural areas (2118(1219-3140) Gg per year) (median and 95% confidence interval) are higher than those in the urban areas (1485(626-2495) Gg per year). The significant relationship (R 2 =0.38, n=29) between the total nitrogen concentrations in lakes and corresponding local nitrogen discharges indicated that, the lakes might be potentially affected by the contaminant inputs from human excreta. The further calculations under two policy scenarios showed that through sanitation improvement, further reduction of nitrogen discharges from human excreta in the developed regions might be limited. The sanitation improvement in the less-developed regions, such as Tibet, Qinghai, and Ningxia, should be considered a priority due to the larger reduction potentials. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Porphyromonas gingivalis Outer Membrane Vesicles Enter Human Epithelial Cells via an Endocytic Pathway and Are Sorted to Lysosomal Compartments ▿

    Furuta, Nobumichi; Tsuda, Kayoko; Omori, Hiroko; Yoshimori, Tamotsu; Yoshimura, Fuminobu; Amano, Atsuo

    2009-01-01

    Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including major fimbriae and proteases termed gingipains, although it is not confirmed whether MVs enter host cells. In this study, we analyzed the mechanisms involved in the interactions of P. gingivalis MVs with human epithelial cells. Our results showed that MVs swiftly adhered to HeLa and immortalized human gingival epithelial cells in a fimbria-dependent manner and then entered via a lipid raft-dependent endocytic pathway. The intracellular MVs were subsequently routed to early endosome antigen 1-associated compartments and then were sorted to lysosomal compartments within 90 min, suggesting that intracellular MVs were ultimately degraded by the cellular digestive machinery. However, P. gingivalis MVs remained there for over 24 h and significantly induced acidified compartment formation after being taken up by the cellular digestive machinery. In addition, MV entry was shown to be mediated by a novel pathway for transmission of bacterial products into host cells, a Rac1-regulated pinocytic pathway that is independent of caveolin, dynamin, and clathrin. Our findings indicate that P. gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis. PMID:19651865

  11. Rabbit defensin (NP-1) genetic engineering of plant

    Jane

    2011-08-22

    Aug 22, 2011 ... rabbit defensin has a significant toxic effect on mouse tumor cells .... Disease is one of the important factors which lead to decrease of .... Transgenic Nitrate Reductase Deficient Mutant of Chlorella ellipsoide. J. Agric.

  12. Enteric glia.

    Rühl, A; Nasser, Y; Sharkey, K A

    2004-04-01

    The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.

  13. Growth and Development Symposium: promoting healthier humans through healthier livestock: animal agriculture enters the metagenomics era.

    Frank, D N

    2011-03-01

    The priorities of public health and agricultural sciences intersect through a shared objective to foster better human health. Enhancements in food quality and reductions in the environmental effects of modern agriculture represent 2 distinct paths through which animal sciences can contribute to the cause of public health. Recent developments in the study of human-associated microbial communities (microbiotas), notably in association with disease, indicate that better understanding of the microbial ecology of livestock can contribute to achieving the goals of better foods and a cleaner environment. Culture-independent microbiological technologies now permit comprehensive study of complex microbial communities in their natural environments. Microbiotas associated with both humans and animals provide myriad beneficial services to their hosts that, if lost or diminished, could compromise host health. Dysfunctional microbial communities have been noted in several human conditions, including inflammatory bowel disease, obesity, and antibiotic-associated diarrhea. Examination of the mechanisms by which the human microbiota influences health and disease susceptibility can inform similar studies of host-microbe function in the animal sciences. Insights gained from human studies indicate strategies to raise not only healthier livestock, through selective manipulation of microbial communities, but also healthier humans.

  14. Plasma alpha-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients

    Joseph, G.; Tarnow, L.; Astrup, A.S.

    2008-01-01

    CONTEXT: alpha-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that alpha-defensins are proatherogenic. OBJECTIVE: The objective of the study was to examine the predictive value of plasma alpha-defensin as a clinical marker of cardiova...... to the development of CVD or an innocent bystander Udgivelsesdato: 2008/4...

  15. Antiplasmodial activity is an ancient and conserved feature of tick defensins

    Alejandro Cabezas-Cruz

    2016-10-01

    Full Text Available Ancestral sequence reconstruction has been widely used to test evolution-based hypotheses. The genome of the European tick vector, Ixodes ricinus, encodes for defensin peptides with diverse antimicrobial activities against distantly related pathogens. These pathogens include fungi, Gram-negative and Gram-positive bacteria, i.e., a wide antimicrobial spectrum. Ticks do not transmit these pathogens, suggesting that these defensins may act against a wide range of microbes encountered by ticks during blood feeding or off-host periods. As demonstrated here, these I. ricinus defensins are also effective against the apicomplexan parasite Plasmodium falciparum. To study the general evolution of antimicrobial activity in tick defensins, the ancestral amino acid sequence of chelicerate defensins, which existed approximately 444 million years ago, was reconstructed using publicly available scorpion and tick defensin sequences (named Scorpions-Ticks Defensins Ancestor, STiDA. The activity of STiDA was tested against P. falciparum and the same Gram-negative and Gram-positive bacteria that were used for the I. ricinus defensins. While some extant tick defensins exhibit a wide antimicrobial spectrum, the ancestral defensin showed moderate activity against one of the tested microbes, P. falciparum. This study suggests that amino acid variability and defensin family expansion increased the antimicrobial spectrum of ancestral tick defensins.

  16. Survival of enteric bacteria in source-separated human urine used ...

    MAKAYA

    Urine in Pumpkin (Cucurbita maxima) Cultivation. Agric. Food Sci. 18:57-68. Pronk W, Koné D (2010). Options for urine treatment in developing countries. Desalination 251:360-368. Schönning C, Leeming R, Stenström TA (2002). Faecal contamination of source-separated human urine based on the content of faecal sterols ...

  17. ATHEANA: open-quotes a technique for human error analysisclose quotes entering the implementation phase

    Taylor, J.; O'Hara, J.; Luckas, W.

    1997-01-01

    Probabilistic Risk Assessment (PRA) has become an increasingly important tool in the nuclear power industry, both for the Nuclear Regulatory Commission (NRC) and the operating utilities. The NRC recently published a final policy statement, SECY-95-126, encouraging the use of PRA in regulatory activities. Human reliability analysis (HRA), while a critical element of PRA, has limitations in the analysis of human actions in PRAs that have long been recognized as a constraint when using PRA. In fact, better integration of HRA into the PRA process has long been a NRC issue. Of particular concern, has been the omission of errors of commission - those errors that are associated with inappropriate interventions by operators with operating systems. To address these concerns, the NRC identified the need to develop an improved HRA method, so that human reliability can be better represented and integrated into PRA modeling and quantification. The purpose of the Brookhaven National Laboratory (BNL) project, entitled 'Improved HRA Method Based on Operating Experience' is to develop a new method for HRA which is supported by the analysis of risk-significant operating experience. This approach will allow a more realistic assessment and representation of the human contribution to plant risk, and thereby increase the utility of PRA. The project's completed, ongoing, and future efforts fall into four phases: (1) Assessment phase (FY 92/93); (2) Analysis and Characterization phase (FY 93/94); (3) Development phase (FY 95/96); and (4) Implementation phase (FY 96/97 ongoing)

  18. Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways

    Lewis D. Evans

    2018-03-01

    Full Text Available Summary: In Alzheimer’s disease, neurofibrillary tangle pathology appears to spread along neuronal connections, proposed to be mediated by the release and uptake of abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is currently unclear whether transfer of tau between neurons is a toxic gain-of-function process in dementia or reflects a constitutive biological process. We report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin-dependent phase typical of endocytosis and a second, slower actin-dependent phase of macropinocytosis. Aggregated tau entry is independent of actin polymerization and largely dynamin dependent, consistent with endocytosis and distinct from macropinocytosis, the major route for aggregated tau entry reported for non-neuronal cells. Anti-tau antibodies abrogate monomeric tau entry into neurons, but less efficiently in the case of aggregated tau, where internalized tau carries antibody with it into neurons. These data suggest that tau entry to human neurons is a physiological process and not a disease-specific phenomenon. : In contrast with predictions that transfer of the microtubule-associated protein tau between neurons is a toxic gain-of-function process in dementia, Evans et al. show that healthy human neurons efficiently take up both normal and aggregated tau, by distinct but overlapping uptake mechanisms. Keywords: Alzheimer’s disease, frontotemporal dementia, Tau, MAPT, iPSC, endocytosis, human neurons, intracellular transport

  19. Yersinia enterocolitica, a Neglected Cause of Human Enteric Infections in Côte d’Ivoire

    Saraka, Daniel; Savin, Cyril; Kouassi, Stephane; Cissé, Bakary; Koffi, Eugène; Cabanel, Nicolas; Brémont, Sylvie; Faye-Kette, Hortense; Dosso, Mireille; Carniel, Elisabeth

    2017-01-01

    Background Enteropathogenic Yersinia circulate in the pig reservoir and are the third bacterial cause of human gastrointestinal infections in Europe. In West Africa, reports of human yersiniosis are rare. This study was conducted to determine whether pathogenic Yersinia are circulating in pig farms and are responsible for human infections in the Abidjan District. Methodology/Principal findings From June 2012 to December 2013, pig feces were collected monthly in 41 swine farms of the Abidjan district. Of the 781 samples collected, 19 Yersinia strains were isolated in 3 farms: 7 non-pathogenic Yersinia intermedia and 12 pathogenic Yersinia enterocolitica bioserotype 4/O:3. Farm animals other than pigs and wild animals were not found infected. Furthermore, 2 Y. enterocolitica 4/O:3 strains were isolated from 426 fecal samples of patients with digestive disorders. All 14 Y. enterocolitica strains shared the same PFGE and MLVA profile, indicating their close genetic relationship. However, while 6 of them displayed the usual phage type VIII, the other 8 had the highly infrequent phage type XI. Whole genome sequencing and SNP analysis of individual colonies revealed that phage type XI strains had unusually high rates of mutations. These strains displayed a hypermutator phenotype that was attributable to a large deletion in the mutS gene involved in DNA mismatch repair. Conclusions/Significance This study demonstrates that pathogenic Y. enterocolitica circulate in the pig reservoir in Côte d'Ivoire and cause human infections with a prevalence comparable to that of many developed countries. The paucity of reports of yersiniosis in West Africa is most likely attributable to a lack of active detection rather than to an absence of the microorganism. The identification of hypermutator strains in pigs and humans is of concern as these strains can rapidly acquire selective advantages that may increase their fitness, pathogenicity or resistance to commonly used treatments. PMID

  20. Yersinia enterocolitica, a Neglected Cause of Human Enteric Infections in Côte d'Ivoire.

    Saraka, Daniel; Savin, Cyril; Kouassi, Stephane; Cissé, Bakary; Koffi, Eugène; Cabanel, Nicolas; Brémont, Sylvie; Faye-Kette, Hortense; Dosso, Mireille; Carniel, Elisabeth

    2017-01-01

    Enteropathogenic Yersinia circulate in the pig reservoir and are the third bacterial cause of human gastrointestinal infections in Europe. In West Africa, reports of human yersiniosis are rare. This study was conducted to determine whether pathogenic Yersinia are circulating in pig farms and are responsible for human infections in the Abidjan District. From June 2012 to December 2013, pig feces were collected monthly in 41 swine farms of the Abidjan district. Of the 781 samples collected, 19 Yersinia strains were isolated in 3 farms: 7 non-pathogenic Yersinia intermedia and 12 pathogenic Yersinia enterocolitica bioserotype 4/O:3. Farm animals other than pigs and wild animals were not found infected. Furthermore, 2 Y. enterocolitica 4/O:3 strains were isolated from 426 fecal samples of patients with digestive disorders. All 14 Y. enterocolitica strains shared the same PFGE and MLVA profile, indicating their close genetic relationship. However, while 6 of them displayed the usual phage type VIII, the other 8 had the highly infrequent phage type XI. Whole genome sequencing and SNP analysis of individual colonies revealed that phage type XI strains had unusually high rates of mutations. These strains displayed a hypermutator phenotype that was attributable to a large deletion in the mutS gene involved in DNA mismatch repair. This study demonstrates that pathogenic Y. enterocolitica circulate in the pig reservoir in Côte d'Ivoire and cause human infections with a prevalence comparable to that of many developed countries. The paucity of reports of yersiniosis in West Africa is most likely attributable to a lack of active detection rather than to an absence of the microorganism. The identification of hypermutator strains in pigs and humans is of concern as these strains can rapidly acquire selective advantages that may increase their fitness, pathogenicity or resistance to commonly used treatments.

  1. Radiation enteritis

    Ochsner, S.F.; Head, L.H.

    1973-01-01

    A comprehensive review of radiation enteritis is presented. Experience in clinical radiation therapy has indicated that the small bowel is the segment of the alimentary tract that is most susceptible to radiation damage. (U.S.)

  2. Physicochemical Factors Influence the Abundance and Culturability of Human Enteric Pathogens and Fecal Indicator Organisms in Estuarine Water and Sediment

    Francis Hassard

    2017-10-01

    Full Text Available To assess fecal pollution in coastal waters, current monitoring is reliant on culture-based enumeration of bacterial indicators, which does not account for the presence of viable but non-culturable or sediment-associated micro-organisms, preventing effective quantitative microbial risk assessment (QMRA. Seasonal variability in viable but non-culturable or sediment-associated bacteria challenge the use of fecal indicator organisms (FIOs for water monitoring. We evaluated seasonal changes in FIOs and human enteric pathogen abundance in water and sediments from the Ribble and Conwy estuaries in the UK. Sediments possessed greater bacterial abundance than the overlying water column, however, key pathogenic species (Shigella spp., Campylobacter jejuni, Salmonella spp., hepatitis A virus, hepatitis E virus and norovirus GI and GII were not detected in sediments. Salmonella was detected in low levels in the Conwy water in spring/summer and norovirus GII was detected in the Ribble water in winter. The abundance of E. coli and Enterococcus spp. quantified by culture-based methods, rarely matched the abundance of these species when measured by qPCR. The discrepancy between these methods was greatest in winter at both estuaries, due to low CFU's, coupled with higher gene copies (GC. Temperature accounted for 60% the variability in bacterial abundance in water in autumn, whilst in winter salinity explained 15% of the variance. Relationships between bacterial indicators/pathogens and physicochemical variables were inconsistent in sediments, no single indicator adequately described occurrence of all bacterial indicators/pathogens. However, important variables included grain size, porosity, clay content and concentrations of Zn, K, and Al. Sediments with greater organic matter content and lower porosity harbored a greater proportion of non-culturable bacteria (including dead cells and extracellular DNA in winter. Here, we show the link between physicochemical

  3. Beta-Defensin-2 and Beta-Defensin-3 Reduce Intestinal Damage Caused by Salmonella typhimurium Modulating the Expression of Cytokines and Enhancing the Probiotic Activity of Enterococcus faecium

    Alessandra Fusco

    2017-01-01

    Full Text Available The intestinal microbiota is a major factor in human health and disease. This microbial community includes autochthonous (permanent inhabitants and allochthonous (transient inhabitants microorganisms that contribute to maintaining the integrity of the intestinal wall, modulating responses to pathogenic noxae and representing a key factor in the maturation of the immune system. If this healthy microbiota is disrupted by antibiotics, chemotherapy, or a change in diet, intestinal colonization by pathogenic bacteria or viruses may occur, leading to disease. To manage substantial microbial exposure, epithelial surfaces of the intestinal tract produce a diverse arsenal of antimicrobial peptides (AMPs, including, of considerable importance, the β-defensins, which directly kill or inhibit the growth of microorganisms. Based on the literature data, the purpose of this work was to create a line of intestinal epithelial cells able to stably express gene encoding human β-defensin-2 (hBD-2 and human β-defensin-3 (hBD-3, in order to test their role in S. typhimurium infections and their interaction with the bacteria of the gut microbiota.

  4. Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes.

    Dorin, Julia R

    2015-01-01

    β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.

  5. Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

    Julia R Dorin

    2015-01-01

    Full Text Available β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.

  6. Combined enteral infusion of glutamine, carbohydrates, and antioxidants modulates gut protein metabolism in humans.

    Coëffier, Moïse; Claeyssens, Sophie; Lecleire, Stéphane; Leblond, Jonathan; Coquard, Aude; Bôle-Feysot, Christine; Lavoinne, Alain; Ducrotté, Philippe; Déchelotte, Pierre

    2008-11-01

    Available data suggest that nutrients can affect intestinal protein metabolism, which contributes to the regulation of gut barrier function. We aimed to assess whether an oral nutritional supplement (ONS) containing glutamine (as the dipeptide Ala-Gln), carbohydrates, and antioxidants would modulate duodenal protein metabolism in healthy humans. Thirty healthy control subjects were included and, over a period of 5 h, received by nasogastric tube either saline or ONS providing 11.7 kcal/kg as 0.877 g Ala-Gln/kg, 3.9 g carbohydrates/kg, and antioxidants (29.25 mg vitamin C/kg, 9.75 mg vitamin E/kg, 195 microg beta-carotene/kg, 5.85 mg Se/kg, and 390 microg Zn/kg) or glutamine (0.585 g/kg, 2.34 kcal/kg). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]-leucine was done until endoscopy. Leucine enrichment was assessed by using gas chromatography-mass spectrometric analysis, and mucosal fractional synthesis rate was calculated by using intracellular amino acid enrichment as precursor. Mucosal proteolytic pathways were also evaluated. ONS infusion resulted in a doubling increase (P < 0.01) of duodenal fractional synthesis rate and a significant (P < 0.05) decrease in cathepsin D-mediated proteolysis compared with saline, whereas proteasome and Ca(2+)-dependent activities were unaffected. ONS infusion significantly (P < 0.01) decreased duodenal glutathione but not glutathione disulfide concentrations or the ratio of glutathione to glutathione disulfide. Insulinemia increased after ONS infusion, whereas plasma essential amino acids decreased. Infusion of glutamine alone did not reproduce ONS effects. ONS infusion improves duodenal protein balance in healthy humans. Further investigations are needed to study the origin of these effects and to evaluate ONS supply in stressed persons.

  7. Endocytic Pathways Used by Andes Virus to Enter Primary Human Lung Endothelial Cells.

    Cheng-Feng Chiang

    Full Text Available Andes virus (ANDV is the major cause of hantavirus pulmonary syndrome (HPS in South America. Despite a high fatality rate (up to 40%, no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection. These genes control the major endocytic pathways, endosomal transport, cell signaling, and cytoskeleton rearrangement. We then used infectious ANDV and retroviral pseudovirions to further characterize the possible involvement of 9 of these genes in the early steps of ANDV entry. In addition, we used markers of cellular endocytosis along with chemical inhibitors of known endocytic pathways to show that ANDV uses multiple routes of entry to infect target cells. These entry mechanisms are mainly clathrin-, dynamin-, and cholesterol-dependent, but can also occur via a clathrin-independent manner.

  8. Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants.

    Stepans, Mary Beth Flanders; Wilhelm, Susan L; Hertzog, Melody; Rodehorst, T Kim Callahan; Blaney, Susan; Clemens, Beth; Polak, Josef J; Newburg, David S

    2006-01-01

    A pilot study tested the relationship between human milk oligosaccharide consumption, oligosaccharide content of feces, and subsequent disease in breastfed infants. Forty-nine (49) mother-infant pairs provided milk and fecal samples 2 weeks postpartum; infant health was assessed through 2, 6, 12, and 24 weeks. LNF-II (lacto-N-fucopentaose II), a major human milk oligosaccharide, was measured to represent levels of total oligosaccharides consumed in milk and remaining in feces. LNF-II levels in milk at 2 weeks postpartum were associated with fewer infant respiratory problems by 6 weeks (p = 0.010), as were LNF-II levels in infant feces (p = 0.003). LNF-II levels in milk at 2 weeks were also associated with fewer respiratory problems by 12 weeks (p = 0.038), and fewer enteric problems by 6 weeks (p = 0.004) and 12 weeks (p = 0.045). Thus, consumption of human milk oligosaccharides through breastfeeding, represented by LNF-II, was associated with less reported respiratory and gastrointestinal illness in infants.

  9. Enteric Duplication.

    Jeziorczak, Paul M; Warner, Brad W

    2018-03-01

    Enteric duplications have been described throughout the entire gastrointestinal tract. The usual perinatal presentation is an abdominal mass. Duplications associated with the foregut have associated respiratory symptoms, whereas duplications in the midgut and hindgut can present with obstructive symptoms, perforation, nausea, emesis, hemorrhage, or be asymptomatic, and identified as an incidental finding. These are differentiated from other cystic lesions by the presence of a normal gastrointestinal mucosal epithelium. Enteric duplications are located on the mesenteric side of the native structures and are often singular with tubular or cystic characteristics. Management of enteric duplications often requires operative intervention with preservation of the native blood supply and intestine. These procedures are usually very well tolerated with low morbidity.

  10. Inactivation of human enteric virus surrogates by high-intensity ultrasound.

    Su, Xiaowei; Zivanovic, Svetlana; D'Souza, Doris H

    2010-09-01

    Foodborne viruses, especially human noroviruses, are recognized as leading causes of nonbacterial gastroenteritis worldwide. Development of effective inactivation methods is of great importance to control their spread. In this study, the effect of high-intensity ultrasound (HIUS) on the infectivity of three foodborne virus surrogates was investigated. The three surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), and MS2 bacteriophage, were diluted in phosphate-buffered saline (PBS) or orange juice to a titer of approximately 6 log(10) PFU/mL or approximately 4 log(10) PFU/mL. The ultrasound treatment was performed in duplicate by immersing the HIUS probe in virus-containing solution that was cooled in ice-water and sonicated at 20 kHz for 2, 5, 10, 15, 20, and 30 min with 30 sec on and 30 sec off. The infectivity of the recovered viruses after each ultrasound treatment was evaluated in duplicate using standardized plaque assays and compared to untreated controls. The results show that HIUS effectiveness depended on the virus type, the initial titer of the viruses, and the virus suspension solution. At titers of approximately 4 log(10) PFU/mL in PBS, feline calicivirus (FCV)-F9, MS2, and murine norovirus (MNV)-1 required 5-, 10-, and 30-min treatment, respectively, for complete inactivation. At initial titers of approximately 4 log(10) PFU/mL in orange juice, FCV-F9 required a 15-min treatment for complete inactivation and only a 1.55 log(10) PFU/mL reduction was achieved for MNV-1 in orange juice after 30-min treatment. Thus, inactivation by HIUS in orange juice was much lower than in PBS. Experiments using titers of approximately 6 log(10) PFU/mL showed decreased effects compared to those using titers of approximately 4 log(10) PFU/mL. These results indicate that HIUS alone is not sufficient to inactivate virus in food. Hurdle technologies that combine HIUS with antimicrobials, heat, or pressure should be explored for viral inactivation.

  11. One-year Surveillance of Human Enteric Viruses in Raw and Treated Wastewaters, Downstream River Waters, and Drinking Waters.

    Iaconelli, M; Muscillo, M; Della Libera, S; Fratini, M; Meucci, L; De Ceglia, M; Giacosa, D; La Rosa, G

    2017-03-01

    Human enteric viruses are a major cause of waterborne diseases, and can be transmitted by contaminated water of all kinds, including drinking and recreational water. The objectives of the present study were to assess the occurrence of enteric viruses (enterovirus, norovirus, adenovirus, hepatitis A and E virus) in raw and treated wastewaters, in rivers receiving wastewater discharges, and in drinking waters. Wastewater treatment plants' (WWTP) pathogen removal efficiencies by adenovirus quantitative real-time PCR and the presence of infectious enterovirus, by cell culture assays, in treated wastewaters and in surface waters were also evaluated. A total of 90 water samples were collected: raw and treated wastewaters (treated effluents and ultrafiltered water reused for industrial purposes), water from two rivers receiving treated discharges, and drinking water. Nested PCR assays were used for the identification of viral DNA/RNA, followed by direct amplicon sequencing. All raw sewage samples (21/21), 61.9 % of treated wastewater samples (13/21), and 25 % of ultrafiltered water samples (3/12) were contaminated with at least one viral family. Multiple virus families and genera were frequently detected. Mean positive PCRs per sample decreased significantly from raw to treated sewage and to ultrafiltered waters. Moreover, quantitative adenovirus data showed a reduction in excess of 99 % in viral genome copies following wastewater treatment. In surface waters, 78.6 % (22/28) of samples tested positive for one or more viruses by molecular methods, but enterovirus-specific infectivity assays did not reveal infectious particles in these samples. All drinking water samples tested negative for all viruses, demonstrating the effectiveness of treatment in removing viral pathogens from drinking water. Integrated strategies to manage water from all sources are crucial to ensure water quality.

  12. Epidemiology, Phylogeny, and Evolution of Emerging Enteric Picobirnaviruses of Animal Origin and Their Relationship to Human Strains

    Yashpal S. Malik

    2014-01-01

    Full Text Available Picobirnavirus (PBV which has been included in the list of viruses causing enteric infection in animals is highly versatile because of its broad host range and genetic diversity. PBVs are among the most recent and emerging small, nonenveloped viruses with a bisegmented double-stranded RNA genome, classified under a new family “Picobirnaviridae.” PBVs have also been detected from respiratory tract of pigs, but needs further close investigation for their inhabitant behavior. Though, accretion of genomic data of PBVs from different mammalian species resolved some of the ambiguity, quite a few questions and hypotheses regarding pathogenesis, persistence location, and evolution of PBVs remain unreciprocated. Evolutionary analysis reveals association of PBVs with partitiviruses especially fungi partitiviruses. Although, PBVs may have an ambiguous clinical implication, they do pose a potential public health concern in humans and control of PBVs mainly relies on nonvaccinal approach. Based upon the published data, from 1988 to date, generated from animal PBVs across the globe, this review provides information and discussion with respect to genetic analysis as well as evolution of PBVs of animal origin in relation to human strains.

  13. α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol.

    Abu-Fanne, Rami; Maraga, Emad; Abd-Elrahman, Ihab; Hankin, Aviel; Blum, Galia; Abdeen, Suhair; Hijazi, Nuha; Cines, Douglas B; Higazi, Abd Al-Roof

    2016-02-05

    Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def(+/+)). Accelerated Def(+/+) mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def(+/+) to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def(+/+) mice prevented these outcomes. The same outcome was obtained by treating Def(+/+) mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Mode of action of plant defensins suggests therapeutic potential

    Thomma, B.P.H.J.; Cammue, B.P.A.; Thevissen, K.

    2003-01-01

    Higher vertebrates can rely both on an innate as well as an adaptive immune system for defense against invading pathogens. In contrast, plants can only employ an innate immune system that largely depends on the production of antimicrobial compounds such as plant defensins and other

  15. Isolation and Properties of Floral Defensins from Ornamental Tobacco and Petunia1

    Lay, Fung T.; Brugliera, Filippa; Anderson, Marilyn A.

    2003-01-01

    The flowers of the solanaceous plants ornamental tobacco (Nicotiana alata) and petunia (Petunia hybrida) produce high levels of defensins during the early stages of development. In contrast to the well-described seed defensins, these floral defensins are produced as precursors with C-terminal prodomains of 27 to 33 amino acids in addition to a typical secretion signal peptide and central defensin domain of 47 or 49 amino acids. Defensins isolated from N. alata and petunia flowers lack the C-terminal domain, suggesting that it is removed during or after transit through the secretory pathway. Immunogold electron microscopy has been used to demonstrate that the N. alata defensin is deposited in the vacuole. In addition to the eight canonical cysteine residues that define the plant defensin family, the two petunia defensins have an extra pair of cysteines that form a fifth disulfide bond and hence define a new subclass of this family of proteins. Expression of the N. alata defensin NaD1 is predominantly flower specific and is most active during the early stages of flower development. NaD1 transcripts accumulate in the outermost cell layers of petals, sepals, anthers, and styles, consistent with a role in protection of the reproductive organs against potential pathogens. The floral defensins inhibit the growth of Botrytis cinerea and Fusarium oxysporum in vitro, providing further support for a role in protection of floral tissues against pathogen invasion. PMID:12644678

  16. Bacterial feeding, Leishmania infection and distinct infection routes induce differential defensin expression in Lutzomyia longipalpis.

    Telleria, Erich L; Sant'Anna, Maurício R Viana; Alkurbi, Mohammad O; Pitaluga, André N; Dillon, Rod J; Traub-Csekö, Yara M

    2013-01-11

    Phlebotomine insects harbor bacterial, viral and parasitic pathogens that can cause diseases of public health importance. Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the New World. Insects can mount a powerful innate immune response to pathogens. Defensin peptides take part in this response and are known to be active against Gram-positive and Gram-negative bacteria, and some parasites. We studied the expression of a defensin gene from Lutzomyia longipalpis to understand its role in sand fly immune response. We identified, sequenced and evaluated the expression of a L. longipalpis defensin gene by semi-quantitative RT-PCR. The gene sequence was compared to other vectors defensins and expression was determined along developmental stages and after exposure of adult female L. longipalpis to bacteria and Leishmania. Phylogenetic analysis showed that the L. longipalpis defensin is closely related to a defensin from the Old World sand fly Phlebotomus duboscqi. Expression was high in late L4 larvae and pupae in comparison to early larval stages and newly emerged flies. Defensin expression was modulated by oral infection with bacteria. The Gram-positive Micrococcus luteus induced early high defensin expression, whilst the Gram-negative entomopathogenic Serratia marcescens induced a later response. Bacterial injection also induced defensin expression in adult insects. Female sand flies infected orally with Leishmania mexicana showed no significant difference in defensin expression compared to blood fed insects apart from a lower defensin expression 5 days post Leishmania infection. When Leishmania was introduced into the hemolymph by injection there was no induction of defensin expression until 72 h later. Our results suggest that L. longipalpis modulates defensin expression upon bacterial and Leishmania infection, with patterns of expression that are distinct among bacterial species and routes of infection.

  17. Human cytochrome c enters murine J774 cells and causes G1 and G2/M cell cycle arrest and induction of apoptosis

    Hiraoka, Yoshinori; Granja, Ana Teresa; Fialho, Arsenio M.; Schlarb-Ridley, Beatrix G.; Das Gupta, Tapas K.; Chakrabarty, Ananda M.; Yamada, Tohru

    2005-01-01

    Cytochrome c is well known as a carrier of electrons during respiration. Current evidence indicates that cytochrome c also functions as a major component of apoptosomes to induce apoptosis in eukaryotic cells as well as an antioxidant. More recently, a prokaryotic cytochrome c, cytochrome c 551 from Pseudomonas aeruginosa, has been shown to enter in mammalian cells such as the murine macrophage-like J774 cells and causes inhibition of cell cycle progression. Much less is known about such functions by mammalian cytochromes c, particularly the human cytochrome c. We now report that similar to P. aeruginosa cytochrome c 551 , the purified human cytochrome c protein can enter J774 cells and induce cell cycle arrest at the G 1 to S phase, as well as at the G 2 /M phase at higher concentrations. Unlike P. aeruginosa cytochrome c 551 which had no effect on the induction of apoptosis, human cytochrome c induces significant apoptosis and cell death in J774 cells, presumably through inhibition of the cell cycle at the G 2 /M phase. When incubated with human breast cancer MCF-7 and normal mammary epithelial cell line MCF-10A1 cells, human cytochrome c entered in both types of cells but induced cell death only in the normal MCF-10A1 cells. The ability of human cytochrome c to enter J774 cells was greatly reduced at 4 deg. C, suggesting energy requirement in the entry process

  18. PaDef defensin from avocado (Persea americana var. drymifolia) is cytotoxic to K562 chronic myeloid leukemia cells through extrinsic apoptosis.

    Flores-Alvarez, Luis José; Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo; Salgado-Garciglia, Rafael; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

    2018-06-01

    Plant defensins, a group of antimicrobial peptides, show selective cytotoxicity toward cancer cells. However, their mechanisms of action remain poorly understood. Here, we evaluated the cytotoxicity of PaDef defensin from avocado (Persea americana var. drymifolia) on K562 chronic myeloid leukemia cells and analyzed the pathway involved in the induction of cell death. The defensin PaDef was not cytotoxic against human PBMCs; however, it was cytotoxic for K562 cell line (IC 50  = 97.3 μg/ml) activating apoptosis at 12 h. PaDef did not affect the mitochondrial membrane potential (ΔΨm), neither the transmembranal potential or the release of intracellular calcium. Also, PaDef induced gene expression of caspase 8 (∼2 fold), TNF-α (∼4 fold) and TNFR1 (∼10 fold). In addition, the activation of caspase 8 was detected at 24 h, whereas caspase 9 activity was not modified, suggesting that the extrinsic apoptosis pathway could be activated. In conclusion, PaDef induces apoptosis on K562 cells, which is related to the activation of caspase 8 and involves the participation of TNF-α, which is a novel property for a plant defensin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Harmonised investigation of the occurrence of human enteric viruses in the leafy green vegetable supply chain in three European countries.

    Kokkinos, P; Kozyra, I; Lazic, S; Bouwknegt, M; Rutjes, S; Willems, K; Moloney, R; de Roda Husman, A M; Kaupke, A; Legaki, E; D'Agostino, M; Cook, N; Rzeżutka, A; Petrovic, T; Vantarakis, A

    2012-12-01

    Numerous outbreaks have been attributed to the consumption of raw or minimally processed leafy green vegetables contaminated with enteric viral pathogens. The aim of the present study was an integrated virological monitoring of the salad vegetables supply chain in Europe, from production, processing and point-of-sale. Samples were collected and analysed in Greece, Serbia and Poland, from 'general' and 'ad hoc' sampling points, which were perceived as critical points for virus contamination. General sampling points were identified through the analysis of background information questionnaires based on HACCP audit principles, and they were sampled during each sampling occasion where as-ad hoc sampling points were identified during food safety fact-finding visits and samples were only collected during the fact-finding visits. Human (hAdV) and porcine (pAdV) adenovirus, hepatitis A (HAV) and E (HEV) virus, norovirus GI and GII (NoV) and bovine polyomavirus (bPyV) were detected by means of real-time (RT-) PCR-based protocols. General samples were positive for hAdV, pAdV, HAV, HEV, NoV GI, NoV GII and bPyV at 20.09 % (134/667), 5.53 % (13/235), 1.32 % (4/304), 3.42 % (5/146), 2 % (6/299), 2.95 % (8/271) and 0.82 % (2/245), respectively. Ad hoc samples were positive for hAdV, pAdV, bPyV and NoV GI at 9 % (3/33), 9 % (2/22), 4.54 % (1/22) and 7.14 % (1/14), respectively. These results demonstrate the existence of viral contamination routes from human and animal sources to the salad vegetable supply chain and more specifically indicate the potential for public health risks due to the virus contamination of leafy green vegetables at primary production.

  20. Radiation enteritis

    Sato, Makoto; Sano, Masanori; Minakuchi, Naoki; Narisawa, Tomio; Takahashi, Toshio

    1981-01-01

    Radiation enteritis with severe complications including intestinal bleeding, fistula, and stenosis were treated surgically in 9 cases. These 9 cases included 7 cases of cancer of the uterine cervix and 2 single cases of seminoma and melanoma. The patients received 60 Co or Linac x-ray external irradiation with or without intracavitary irradiation by a radium needle. Radiation injury began with melena, vaginorectal fistula, and intestinal obstruction 3 to 18 months after irradiation. One patient with melena underwent colostomy and survived 2 years. One of the three patients with vaginorectal fistula who had colostomy survived 1.5 years. In intestinal obstruction, one patients had bypass operation and three patients had resection of the intestine and the other had both. Leakage was noted in one patient, but the others had favorable prognosis. (Ueda, J.)

  1. Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin.

    Patrick A M Jansen

    Full Text Available BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2 is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.

  2. Ixodes ricinus defensins attack distantly-related pathogens

    Tonk, M.; Cabezas-Cruz, A.; Valdés, James J.; Rego, Ryan O. M.; Grubhoffer, Libor; Estrada--Pena, A.; Vilcinskas, A.; Kotsyfakis, Michalis; Rahnamaeian, M.

    2015-01-01

    Roč. 53, č. 2 (2015), s. 358-365 ISSN 0145-305X R&D Projects: GA MŠk(CZ) EE2.3.30.0032; GA ČR GAP502/12/2409 EU Projects: European Commission(XE) 278976 Institutional support: RVO:60077344 Keywords : Antimicrobial peptide * Defensin * Ixodes ricinus * Listeria monocytogenes * Staphylococcus aureus * Staphylococcus epidermidis * Escherichia coli * Pseudomonas aeruginosa * Fusarium spp Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.620, year: 2015

  3. Structural and functional characterization of the conserved salt bridge in mammalian paneth cell alpha-defensins

    Rosengren, K Johan; Daly, Norelle L; Fornander, Liselotte M

    2006-01-01

    alpha-Defensins are mediators of mammalian innate immunity, and knowledge of their structure-function relationships is essential for understanding their mechanisms of action. We report here the NMR solution structures of the mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) and a mutant (E15D)-C...

  4. Characterization of defensin gene from abalone Haliotis discus hannai and its deduced protein

    Hong, Xuguang; Sun, Xiuqin; Zheng, Minggang; Qu, Lingyun; Zan, Jindong; Zhang, Jinxing

    2008-11-01

    Defensin is one of preserved ancient host defensive materials formed in biological evolution. As a regulator and effector molecule, it is very important in animals’ acquired immune system. This paper reports the defensin gene from the mixed liver and kidney cDNA library of abalone Haliotis discus hannai Ino. Sequence analysis shows that the gene sequence of full-length cDNA encodes 42 mature peptides (including six Cys), molecular weight of 4 323 Da, and pI of 8.02. Amino acid sequence homology analysis shows that the peptides are highly similar (70% in common) to other insects defensin. Because of a typical insect-defensin structural character of mature peptide in the secondary structure, the polypeptide named Haliotis discus defensin (hd-def), a novel of antimicrobial peptides, belongs to insects defensin subfamily. The RT-PCR result of Haliotis discus defensin shows that the gene can be expressed only in the hepatopancreas by Gram-negative and positive bacteria stimulation, which is ascribed to inducible expression. Therefore, it is revealed that the Haliotis discus defensin gene expression was related to the antibacterial infection of Haliotis discus hannai Ino.

  5. Expression and antimicrobial function of beta-defensin 1 in the lower urinary tract.

    Brian Becknell

    Full Text Available Beta defensins (BDs are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1 expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1(-/- mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1(-/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

  6. Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract

    Becknell, Brian; Spencer, John David; Carpenter, Ashley R.; Chen, Xi; Singh, Aspinder; Ploeger, Suzanne; Kline, Jennifer; Ellsworth, Patrick; Li, Birong; Proksch, Ehrhardt; Schwaderer, Andrew L.; Hains, David S.; Justice, Sheryl S.; McHugh, Kirk M.

    2013-01-01

    Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1 -/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1 -/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract. PMID:24204930

  7. Cross-Comparison of Human Wastewater-Associated Molecular Markers in Relation to Fecal Indicator Bacteria and Enteric Viruses in Recreational Beach Waters.

    Hughes, B; Beale, D J; Dennis, P G; Cook, S; Ahmed, W

    2017-04-15

    Detection of human wastewater contamination in recreational waters is of critical importance to regulators due to the risks posed to public health. To identify such risks, human wastewater-associated microbial source tracking (MST) markers have been developed. At present, however, a greater understanding of the suitability of these markers for the detection of diluted human wastewater in environmental waters is necessary to predict risk. Here, we compared the process limit of detection (PLOD) and process limit of quantification (PLOQ) of six human wastewater-associated MST markers ( Bacteroides HF183 [HF183], Escherichia coli H8 [EC H8], Methanobrevibacter smithii nifH , human adenovirus [HAdV], human polyomavirus [HPyV], and pepper mild mottle virus [PMMoV]) in relation to a fecal indicator bacterium (FIB), Enterococcus sp. 23S rRNA (ENT 23S), and three enteric viruses (human adenovirus serotypes 40/41 [HAdV 40/41], human norovirus [HNoV], and human enterovirus [EV]) in beach water samples seeded with raw and secondary-treated wastewater. Among the six MST markers tested, HF183 was the most sensitive measure of human fecal pollution and was quantifiable up to dilutions of 10 -6 and 10 -4 for beach water samples seeded with raw and secondary-treated wastewater, respectively. Other markers and enteric viruses were detected at various dilutions (10 -1 to 10 -5 ). These MST markers, FIB, and enteric viruses were then quantified in beach water ( n = 12) and sand samples ( n = 12) from South East Queensland (SEQ), Australia, to estimate the levels of human fecal pollution. Of the 12 sites examined, beach water and sand samples from several sites had quantifiable concentrations of HF183 and PMMoV markers. Overall, our results indicate that while HF183 is the most sensitive measure of human fecal pollution, it should be used in conjunction with a conferring viral marker to avoid overestimating the risk of gastrointestinal illness. IMPORTANCE MST is an effective tool to

  8. C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins.

    Simpson-Abelson, Michelle R; Childs, Erin E; Ferreira, M Carolina; Bishu, Shrinivas; Conti, Heather R; Gaffen, Sarah L

    2015-01-01

    Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream events that control immunity to this fungus are poorly understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBPβ is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBPβ in vivo is poorly understood, in part because C/EBPβ-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBPβ in the context of an IL-17-dependent immune response, using C. albicans infection as a model system. Confirming prior findings, we found that C/EBPβ is required for immunity to systemic candidiasis. In contrast, C/EBPβ(-/-) mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBPβ(-/-) mice experienced more severe OPC than WT mice in the context of cortisone-induced immunosuppression. Expression of the antimicrobial peptide β-defensin (BD)-3 correlated strongly with susceptibility in C/EBPβ(-/-) mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBPβ contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to β-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response.

  9. Comparison of the effects of enteral feeding with continuous and intermittent parenteral nutrition on hepatic triglyceride secretion in human beings

    Isabel-Martinez, L.; Skinner, C.; Parkin, A.; Hall, R.I.

    1989-01-01

    Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained by deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion

  10. Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

    Jespersgaard, Cathrine; Fode, Peder; Dybdahl, Marianne

    2011-01-01

    BACKGROUND AND PURPOSE OF STUDY: Extensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1-3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn's disease (CD) patients and the possible genetic association...... of DEFA1A3 with CD. METHODS: Two-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy...

  11. First molecular characterization of enteric protozoa and the human pathogenic microsporidian, Enterocytozoon bieneusi, in captive snakes in China.

    Karim, Md Robiul; Yu, Fuchang; Li, Jian; Li, Junqiang; Zhang, Longxian; Wang, Rongjun; Rume, Farzana Islam; Jian, Fuchun; Zhang, Sumei; Ning, Changshen

    2014-08-01

    Enteric protozoa are frequently found in snakes. Nevertheless, few studies regarding genetic characterization of these parasites have been carried out. We describe here the first molecular survey of protozoan pathogens from snakes in China and the first report on Enterocytozoon bieneusi genotyping in snakes in the world. Here, 240 fecal specimens were collected from two species of captive snakes, Naja naja (Indian cobra) and Ptyas mucosus (Oriental rat snake), in Guangxi Province, China, and examined by PCR amplification of the small subunit-ribosomal RNA of enteric protozoa and the internal transcribed spacer of ribosomal RNA of E. bieneusi. Cryptosporidium serpentis was identified in three specimens (2.1%) of Oriental rat snakes. Caryospora was found in 5.4% specimens, including eight from cobras (8.1%) and five from rat snakes (3.6%), and represented six new species-Caryospora sp. SKC-2014a to Caryospora sp. SKC-2014 f. Three new Eimeria species, Eimeria sp. SKE-2014a to Eimeria sp. SKE-2014c, were detected in three specimens (2.1%) from rat snakes. Additionally, Sarcocystis sp. SKS-2014 was detected in one specimen from a cobra. The infection rates of E. bieneusi were 3.0% in cobras and 5.7% in rat snakes. Sequence analysis of 11 PCR products revealed the presence of six E. bieneusi genotypes-two known genotypes (type IV and Henan V) and four new genotypes (CRep-1 to CRep-4). All six E. bieneusi genotypes belonged to the zoonotic group (group 1). This result raised the possibility that E. bieneusi could be present in animals consumed by snakes. This should be taken into consideration to better understand the diversity of the parasite, its transmission through the predator-prey relationship, and public health implications.

  12. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease

    Aldhous, Marian C.; Abu Bakar, Suhaili; Prescott, Natalie J.; Palla, Raquel; Soo, Kimberley; Mansfield, John C.; Mathew, Christopher G.; Satsangi, Jack; Armour, John A.L.

    2010-01-01

    The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case–control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case–control studies. PMID:20858604

  13. Association studies of the copy-number variable ß-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis

    Taudien Stefan

    2012-11-01

    Full Text Available Abstract Background Human ß-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV and copy-number variants (CNV of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case–control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF cluster copy number (CN, and pancreatic ductal adenocarcinoma (PDAC and chronic pancreatitis (CP. Results Two groups of PDAC (N=70 and CP (N=60 patients were compared to matched healthy control groups CARLA1 (N=232 and CARLA2 (N=160, respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification. Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively. The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher’s exact test P=0.027, but not between CP and CARLA2 (P=0.867. Conclusion Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.

  14. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease.

    Aldhous, Marian C; Abu Bakar, Suhaili; Prescott, Natalie J; Palla, Raquel; Soo, Kimberley; Mansfield, John C; Mathew, Christopher G; Satsangi, Jack; Armour, John A L

    2010-12-15

    The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies.

  15. Successful in vitro expansion and Characterization of Human Enteric Neuronal cells- A step towards Cell based therapies for Hirschsprung’s disease

    Balamurugan M

    2010-01-01

    Full Text Available BACKGROUND: The Enteric Nervous system (ENS is a part of the Peripheral nervous system (PNS that controls the peristaltic activity of the gut wall which is essential for propulsion of food in the digestive tract. It is composed of a large number of neurons and glial cells, distributed throughout the length of the gut. These ganglion cells develop from the neural crest in the embryo. Failure of complete colonization of the gut by these enteric neural crest cells during early development of life results in absence of ganglia or neurons in a portion of the gut, usually the colon which leads to aperistaltis and severe intestinal obstruction. This is known as Hirschsprung’s disease (HSCR also known as congenital megacolon. HSCR affects 1 in 4500 newborns (1, 2. It appears either sporadically or has a familial basis and is often associated with other developmental defects. The main forms of treatment of HSCR are surgical resection of the aganglionic segment and pull through of the normal bowel. At present research is aimed at developing Cell based therapies for replacement of ganglion cells or enteric neuronal cells in the aganglionic portion of the gut thus aiming at restoring the function of the gut (1, 3, 5. In this study we have isolated, in vitro expanded and characterized the Enteric Neuronal cells derived from human gut full thickness biopsy samplesMATERIALS AND METHODS: The postnatal gut full thickness biopsy samples of size 2-4 mm were obtained using from 13 patients undergoing gut resection surgery after informed consent. The samples were washed in Phosphate Buffer saline and using forceps, the outer smooth muscle layers along with the myenteric plexus were peeled off from the underlying tissue as strips. The strips were washed in Phosphate Buffer saline (PBS and treated with 1mg/ml Collagenase/Dispase mixture in PBS for 30-45 min at 37°C. The digested cells were filtered with 70µm filter and the cell suspensions were centrifuged at 1800

  16. ANTIMICROBIAL RESISTANCE AMONG ENTERIC BACTERIA ISOLATED FROM HUMAN AND ANIMAL WASTES AND IMPACTED SURFACE WATERS: COMPARISON WITH NARMS FINDINGS

    Human infection with bacteria exhibiting mono or multiple antimicrobial resistance (MAR) has been a growing problem in the US, and studies have implicated livestock as a source of MAR bacteria primarily through foodborne transmission routes. However, waterborne transmission of...

  17. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  18. Antibacterial and antiviral roles of a fish β-defensin expressed both in pituitary and testis.

    Jun-Yan Jin

    Full Text Available Defensins are a group of cationic peptides that exhibit broad-spectrum antimicrobial activity. In this study, we cloned and characterized a β-defensin from pituitary cDNA library of a protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides. Interestingly, the β-defensin was shown to be dominantly expressed in pituitary and testis by RT-PCR and Western blot analysis, and its transcript level is significantly upregulated in reproduction organs from intersexual gonad to testis during the natural and artificial sex reversal. Promoter sequence and the responsible activity region analyses revealed the pituitary-specific POU1F1a transcription binding site and testis-specific SRY responsible site, and demonstrated that the pituitary-specific POU1F1a transcription binding site that locates between -180 and -208 bp is the major responsible region of grouper β-defensin promoter activity. Immunofluorescence localization observed its pituicyte expression in pituitary and spermatogonic cell expression in testis. Moreover, both in vitro antibacterial activity assay of the recombinant β-defensin and in vivo embryo microinjection of the β-defensin mRNA were shown to be effective in killing gram-negative bacteria. And, its antiviral role was also demonstrated in EPC cells transfected with the β-defensin construct. Additionally, the antibacterial activity was sensitive to concentrations of Na(+, K(+, Ca(2+ and Mg(2+. The above intriguing findings strongly suggest that the fish β-defensin might play significant roles in both innate immunity defense and reproduction endocrine regulation.

  19. Antibacterial and antiviral roles of a fish β-defensin expressed both in pituitary and testis.

    Jin, Jun-Yan; Zhou, Li; Wang, Yang; Li, Zhi; Zhao, Jiu-Gang; Zhang, Qi-Ya; Gui, Jian-Fang

    2010-12-20

    Defensins are a group of cationic peptides that exhibit broad-spectrum antimicrobial activity. In this study, we cloned and characterized a β-defensin from pituitary cDNA library of a protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides). Interestingly, the β-defensin was shown to be dominantly expressed in pituitary and testis by RT-PCR and Western blot analysis, and its transcript level is significantly upregulated in reproduction organs from intersexual gonad to testis during the natural and artificial sex reversal. Promoter sequence and the responsible activity region analyses revealed the pituitary-specific POU1F1a transcription binding site and testis-specific SRY responsible site, and demonstrated that the pituitary-specific POU1F1a transcription binding site that locates between -180 and -208 bp is the major responsible region of grouper β-defensin promoter activity. Immunofluorescence localization observed its pituicyte expression in pituitary and spermatogonic cell expression in testis. Moreover, both in vitro antibacterial activity assay of the recombinant β-defensin and in vivo embryo microinjection of the β-defensin mRNA were shown to be effective in killing gram-negative bacteria. And, its antiviral role was also demonstrated in EPC cells transfected with the β-defensin construct. Additionally, the antibacterial activity was sensitive to concentrations of Na(+), K(+), Ca(2+) and Mg(2+). The above intriguing findings strongly suggest that the fish β-defensin might play significant roles in both innate immunity defense and reproduction endocrine regulation.

  20. Inflammatory disorders mimicking periprosthetic joint infections may result in false positive α-defensin.

    Plate, Andreas; Stadler, Laura; Sutter, Reto; Anagnostopoulos, Alexia; Frustaci, Dario; Zbinden, Reinhard; Fucentese, Sandro F; Zinkernagel, Annelies S; Zingg, Patrick O; Achermann, Yvonne

    2018-02-26

    The antimicrobial peptide α-defensin has recently been introduced as potential "single" biomarker with a high sensitivity and specificity for the preoperative diagnosis of periprosthetic joint infections (PJIs). However, most studies assessed the benefits of the test with exclusion of patients with rheumatic diseases. We aimed to evaluate the α-defensin test in a cohort study without exclusion of cases with inflammatory diseases. Between June 2016 and June 2017, we prospectively included cases with a suspected PJI and an available lateral flow test α-defensin (Synovasure®) in synovial fluid. We compared the test result to the diagnostic criteria for PJIs published by an International Consensus Group in 2013. We included 109 cases (49 hips, 60 knees) in which preoperative α-defensin tests had been performed. Thereof, 20 PJIs (16 hips, 4 knees) were diagnosed. Preoperative α-defensin tests were positive in 25 cases (22.9%) with a test sensitivity and specificity of 90% and 92.1% (95% confidence interval [CI], 68.3 - 98.8% and 84.5 - 96.8%, respectively), and a high negative predictive value of 97.6% (95% CI, 91.7 - 99.4%). We interpreted seven α-defensin tests as false positive, mainly in cases with inflammatory rheumatic diseases, including crystal deposition diseases. A negative synovial α-defensin test can reliably rule out a PJI. However, the test can be false positive in conjunction with an underlying non-infectious inflammatory disease. We therefore propose to use the α-defensin test only in addition to MSIS criteria and assessment for crystals in synovial aspirates. Copyright © 2018. Published by Elsevier Ltd.

  1. Differential expression of human beta defensins in placenta and detection of allelic variants in the DEFB1 gene from HIV-1 positive mothers Expresión diferencial en placenta de beta-defensinas humanas y detección de variantes alélicas en el gen DEFB1 de madres positivas para VIH-1

    María Teresa Rugeles

    2011-04-01

    Full Text Available Introduction. Low infection rates in neonates born to HIV-1-seropositive mothers highlight the existence of natural defense mechanisms in the maternal-fetal interface. Human beta defensins (HBDs inhibit HIV-1 replication in vitro and their variants are associated with HIV-1 resistance/susceptibility.
    Objective. Levels of HBD mRNA expression in placentas were obtained from seropositive and healthy mothers to determine whether HIV-1 infection induces anti-viral factors.
    Materials and methods. HBD-1, -2 and -3 transcripts were quantified by real time RT-PCR, and A692G/G1654A/A1836G variants in the DEFB1 gene were evaluated by sequencing.
    Results. Transcript levels of HBD-1 were significantly higher, and those of HBD-3 were lower in placenta from seropositive mothers compared to controls. Additionally, simultaneous presence of the A692G A/G and A1836G G/G genotypes was associated with high expression of HBD-1 in all populations and the A692G variant in babies born to seropositive mothers was in Hardy-Weinberg disequilibrium.
    Conclusion. Contrasting results in levels of HBDs were probably due to viral stimuli and suggest that HIV-1 induce a differential expression of HBDs in placenta and these proteins could be involved in protecting against HIV-1 at least early in pregnancy. However, it was not possible to associate these findings directly with protection against HIV-1 vertical transmission since none of the newborn infants became infected.
    Introducción. Las bajas tasas de infección en neonatos nacidos de madres seropositivas para el VIH-1 resaltan la existencia de mecanismos de defensa natural en la interfase materno-fetal. Las beta-defensinas humanas inhiben la replicación del VIH-1 in vitro y sus polimorfismos están asociados con la resistencia o susceptibilidad al VIH-1.
    Objetivo. Comparar los niveles de expresión de ARNm de beta-defensinas humanas en placentas de madres seropositivas y en seronegativas para

  2. Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study

    Anthonisen Nicholas R

    2006-05-01

    Full Text Available Abstract Background Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function. Methods Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile. Results There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection. Conclusion These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections.

  3. Enteral delivery of proteins stimulates protein synthesis in human duodenal mucosa in the fed state through a mammalian target of rapamycin-independent pathway.

    Coëffier, Moïse; Claeyssens, Sophie; Bôle-Feysot, Christine; Guérin, Charlène; Maurer, Brigitte; Lecleire, Stéphane; Lavoinne, Alain; Donnadieu, Nathalie; Cailleux, Anne-Françoise; Déchelotte, Pierre

    2013-02-01

    Glutamine modulates duodenal protein metabolism in fasted healthy humans, but its effects in a fed state remain unknown. We aimed to assess the effects of either glutamine or an isonitrogenous protein mixture on duodenal protein metabolism in humans in the fed state. Twenty-four healthy volunteers were randomly included in 2 groups. Each volunteer was studied on 2 occasions in a random order and received, during 5 h, either an enteral infusion of maltodextrins alone (0.25 g · kg⁻¹ · h⁻¹; both groups) that mimicked a carbohydrate fed state or maltodextrins with glutamine (group 1) or an isonitrogenous (22.4 mg N · kg⁻¹ · h⁻¹) protein powder (group 2). Simultaneously, a continuous intravenous infusion of ¹³C-leucine and ²H₅-phenylalanine (both 9 μmol · kg⁻¹ · h⁻¹) was performed. Endoscopic duodenal biopsies were taken. Leucine and phenylalanine enrichments were assessed by using gas chromatography-mass spectrometry in duodenal proteins and the intracellular free amino acids pool to calculate the mucosal fractional synthesis rate (FSR). Proteasome proteolytic activities and phosphokinase expression were assessed by using specific fluorogenic substrates and macroarrays, respectively. The FSR and proteasome activity were not different after the glutamine supply compared with after maltodextrins alone. In contrast, the FSR increased (1.7-fold increase; P protein-powder delivery without modification of total proteasome activity. The protein powder increased insulinemia, PI3 kinase, and erk phosphorylation but did not affect the mammalian target of rapamycin (mTOR) pathway and mitogen-activated protein kinase signal-integrating kinase 1 phosphorylation. A trend for an increase of eukaryotic translation initiation factor 4E phosphorylation was observed (P = 0.07). In the carbohydrate fed state, enteral proteins but not glutamine increased duodenal protein synthesis through an mTOR independent pathway in humans.

  4. In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study.

    Susan Hetz

    Full Text Available Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH. For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu and immunohistochemistry (PGP9.5, GFAP, SMA. In addition, we determined nitric oxide synthase (NOS-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be

  5. Molecular assays for targeting human and bovine enteric viruses in coastal waters and their application for library-independent source tracking

    Fong, T.-T.; Griffin, Dale W.; Lipp, E.K.

    2005-01-01

    Rapid population growth and urban development along waterways and coastal areas have led to decreasing water quality. To examine the effects of upstream anthropogenic activities on microbiological water quality, methods for source-specific testing are required. In this study, molecular assays targeting human enteroviruses (HEV), bovine enteroviruses (BEV), and human adenoviruses (HAdV) were developed and used to identify major sources of fecal contamination in the lower Altamaha River, Georgia. Two-liter grab samples were collected monthly from five tidally influenced stations between July and December 2002. Samples were analyzed by reverse transcription- and nested-PCR. PCR results were confirmed by dot blot hybridization. Eleven and 17 of the 30 surface water samples tested positive for HAdV and HEV, respectively. Two-thirds of the samples tested positive for either HEV or HAdV, and the viruses occurred simultaneously in 26% of samples. BEV were detected in 11 of 30 surface water samples. Binary logistic regression analysis showed that the presence of both human and bovine enteric viruses was not significantly related to either fecal coliform or total coliform levels. The presence of these viruses was directly related to dissolved oxygen and streamflow but inversely related to water temperature, rainfall in the 30 days preceding sampling, and chlorophyll-?? concentrations. The stringent host specificity of enteric viruses makes them good library-independent indicators for identification of water pollution sources. Viral pathogen detection by PCR is a highly sensitive and easy-to-use tool for rapid assessment of water quality and fecal contamination when public health risk characterization is not necessary. Copyright ?? 2005, American Society for Microbiology. All Rights Reserved.

  6. Evaluation of the suitability of a plant virus, pepper mild mottle virus, as a surrogate of human enteric viruses for assessment of the efficacy of coagulation-rapid sand filtration to remove those viruses.

    Shirasaki, N; Matsushita, T; Matsui, Y; Yamashita, R

    2018-02-01

    Here, we evaluated the removal of three representative human enteric viruses - adenovirus (AdV) type 40, coxsackievirus (CV) B5, and hepatitis A virus (HAV) IB - and one surrogate of human caliciviruses - murine norovirus (MNV) type 1 - by coagulation-rapid sand filtration, using water samples from eight water sources for drinking water treatment plants in Japan. The removal ratios of a plant virus (pepper mild mottle virus; PMMoV) and two bacteriophages (MS2 and φX174) were compared with the removal ratios of human enteric viruses to assess the suitability of PMMoV, MS2, and φX174 as surrogates for human enteric viruses. The removal ratios of AdV, CV, HAV, and MNV, evaluated via the real-time polymerase chain reaction (PCR) method, were 0.8-2.5-log 10 when commercially available polyaluminum chloride (PACl, basicity 1.5) and virgin silica sand were used as the coagulant and filter medium, respectively. The type of coagulant affected the virus removal efficiency, but the age of silica sand used in the rapid sand filtration did not. Coagulation-rapid sand filtration with non-sulfated, high-basicity PACls (basicity 2.1 or 2.5) removed viruses more efficiently than the other aluminum-based coagulants. The removal ratios of MS2 were sometimes higher than those of the three human enteric viruses and MNV, whereas the removal ratios of φX174 tended to be smaller than those of the three human enteric viruses and MNV. In contrast, the removal ratios of PMMoV were similar to and strongly correlated with those of the three human enteric viruses and MNV. Thus, PMMoV appears to be a suitable surrogate for human enteric viruses for the assessment of the efficacy of coagulation-rapid sand filtration to remove viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. In vitro culture and characterization of enteric neural precursor cells from human gut biopsy specimens using polymer scaffold.

    Krishnamohan, Janardhanam; Senthilnathan, Venugopal S; Vaikundaraman, Tirunelveli Muthiah; Srinivasan, Thangavelu; Balamurugan, Madasamy; Iwasaki, Masaru; Preethy, Senthilkumar; Abraham, Samuel Jk

    2013-08-01

    In vitro expansion and characterization of neural precursor cells from human gut biopsy specimens with or without Hirschsprung's disease using a novel thermoreversible gelation polymer (TGP) is reported aiming at a possible future treatment. Gut biopsy samples were obtained from five patients undergoing gut resection for Hirschsprung's disease (n = 1) or gastrointestinal disorders (n = 4). Cells isolated from the smooth muscle layer and the myenteric plexus were cultured in two groups for 18 to 28 days; Group I: conventional culture as earlier reported and Group II: using TGP scaffold. Neurosphere like bodies (NLBs) were observed in the cultures between 8th to 12th day and H & E staining was positive for neural cells in both groups including aganglionic gut portion from the Hirschsprung's disease patient. Immunohistochemistry using S-100 and neuron specific enolase (NSE) was positive in both groups but the TGP group (Group II) showed more number of cells with intense cytoplasmic granular positivity for both NSE and S-100 compared to Group I. TGP supports the in vitro expansion of human gut derived neuronal cells with seemingly better quality NLBs. Animal Studies can be tried to validate their functional outcome by transplanting the NLBs with TGP scaffolds to see whether this can enhance the outcome of cell based therapies for Hirschsprung's disease.

  8. Ha-DEF1, a sunflower defensin, induces cell death in Orobanche parasitic plants.

    de Zélicourt, Axel; Letousey, Patricia; Thoiron, Séverine; Campion, Claire; Simoneau, Philippe; Elmorjani, Khalil; Marion, Didier; Simier, Philippe; Delavault, Philippe

    2007-08-01

    Plant defensins are small basic peptides of 5-10 kDa and most of them exhibit antifungal activity. In a sunflower resistant to broomrape, among the three defensin encoding cDNA identified, SF18, SD2 and HaDef1, only HaDef1 presented a preferential root expression pattern and was induced upon infection by the root parasitic plant Orobanche cumana. The amino acid sequence deduced from HaDef1 coding sequence was composed of an endoplasmic reticulum signal sequence of 28 amino acids, a standard defensin domain of 50 amino-acid residues and an unusual C-terminal domain of 30 amino acids with a net positive charge. A 5.8 kDa recombinant mature Ha-DEF1 corresponding to the defensin domain was produced in Escherichia coli and was purified by means of a two-step chromatography procedure, Immobilized Metal Affinity Chromatography (IMAC) and Ion Exchange Chromatography. Investigation of in vitro antifungal activity of Ha-DEF1 showed a strong inhibition on Saccharomyces cerevisiae growth linked to a membrane permeabilization, and a morphogenetic activity on Alternaria brassicicola germ tube development, as already reported for some other plant defensins. Bioassays also revealed that Ha-DEF1 rapidly induced browning symptoms at the radicle apex of Orobanche seedlings but not of another parasitic plant, Striga hermonthica, nor of Arabidopsis thaliana. FDA vital staining showed that these browning areas corresponded to dead cells. These results demonstrate for the first time a lethal effect of defensins on plant cells. The potent mode of action of defensin in Orobanche cell death and the possible involvement in sunflower resistance are discussed.

  9. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: identification of an RGFRRR motif governing fungal cell entry.

    Uma Shankar Sagaram

    Full Text Available MtDef4 is a 47-amino acid cysteine-rich evolutionary conserved defensin from a model legume Medicago truncatula. It is an apoplast-localized plant defense protein that inhibits the growth of the ascomycetous fungal pathogen Fusarium graminearum in vitro at micromolar concentrations. Little is known about the mechanisms by which MtDef4 mediates its antifungal activity. In this study, we show that MtDef4 rapidly permeabilizes fungal plasma membrane and is internalized by the fungal cells where it accumulates in the cytoplasm. Furthermore, analysis of the structure of MtDef4 reveals the presence of a positively charged γ-core motif composed of β2 and β3 strands connected by a positively charged RGFRRR loop. Replacement of the RGFRRR sequence with AAAARR or RGFRAA abolishes the ability of MtDef4 to enter fungal cells, suggesting that the RGFRRR loop is a translocation signal required for the internalization of the protein. MtDef4 binds to phosphatidic acid (PA, a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Amino acid substitutions in the RGFRRR sequence which abolish the ability of MtDef4 to enter fungal cells also impair its ability to bind PA. These findings suggest that MtDef4 is a novel antifungal plant defensin capable of entering into fungal cells and affecting intracellular targets and that these processes are mediated by the highly conserved cationic RGFRRR loop via its interaction with PA.

  10. Challenging metastatic breast cancer with the natural defensin PvD1.

    Figueira, Tiago N; Oliveira, Filipa D; Almeida, Inês; Mello, Érica O; Gomes, Valdirene M; Castanho, Miguel A R B; Gaspar, Diana

    2017-11-09

    Metastatic breast cancer is a very serious life threatening condition that poses many challenges for the pharmaceutical development of effective chemotherapeutics. As the therapeutics targeted to the localized masses in breast improve, metastatic lesions in the brain slowly increase in their incidence compromising successful treatment outcomes overall. The blood-brain-barrier (BBB) is one important obstacle for the management of breast cancer brain metastases. New therapeutic approaches are in demand for overcoming the BBB's breaching by breast tumor cells. In this work we demonstrate the potential dual role of a natural antimicrobial plant defensin, PvD 1 : it interferes with the formation of solid tumors in the breast and concomitantly controls adhesion of breast cancer cells to human brain endothelial cells. We have used a combination of techniques that probe PvD 1 's effect at the single cell level and reveal that this peptide can effectively damage breast tumor cells, leaving healthy breast and brain cells unaffected. Results suggest that PvD1 quickly internalizes in cancer cells but remains located in the membrane of normal cells with no significant damage to its structure and biomechanical properties. These interactions in turn modulate cell adhesiveness between tumor and BBB cells. PvD 1 is a potential template for the design of innovative pharmacological approaches for metastatic breast cancer treatment: the manipulation of the biomechanical properties of tumor cells that ultimately prevent their attachment to the BBB.

  11. Induction of CTGF by TGF-β1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives

    Haydont, Valerie; Mathe, Denis; Bourgier, Celine; Abdelali, Jalil; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

    2005-01-01

    Background and purpose: Transforming Growth Factor β1 (TGF-β1) and its downstream effector Connective Tissue Growth Factor (CTGF/CCN2), are well known fibrogenic activators and we previously showed that the Rho/ROCK pathway controls CTGF expression in intestinal smooth muscle cells isolated from patients with delayed radiation enteritis. The aim of the present work was to investigate the balance between Smad and Rho signalling pathways in the TGF-β1 CTGF induction and modulation of radiation-induced fibrogenic differentiation after addition of pravastatin, an inhibitor of Rho isoprenylation. Patients and methods: Primary human smooth muscle cells isolated from normal (N-SMC) or radiation enteritis (RE-SMC) biopsies were incubated with TGF-β1 (10 ng/ml). Induction of CTGF, as well as nucleo-cytoplasmic distribution of phospho-Smad2/3, Smad2/3 and Smad4 were analysed by Western blot and immunocytochemistry. Smad DNA binding was assessed by EMSA and Rho activation was measured by pull-down assay. Results: After TGF-β1 addition, Smads were translocated to the nucleus in both cell types. Nuclear accumulation of Smad as well as their DNA-binding activity were higher in N-SMC than in RE-SMC, whereas the opposite was observed for Rho activation, suggesting a main involvement of Rho pathway in sustained fibrogenic differentiation. This hypothesis was further supported by the antifibrotic effect observed in vitro after cell treatment with pravastatin (i.e. decreased expression of CTGF, TGF-β1 and Collagen Iα2). Conclusions: Our results suggest that TGF-β1-induced CTGF transactivation mainly depends on the Smad pathway in N-SMC, whereas in RE-SMC, Smad and Rho pathways are involved. Inhibition of Rho activity by pravastatin alters fibrogenic differentiation in vitro which opens up new therapeutic perspectives

  12. α-Defensins and outcome in patients with chronic heart failure

    Christensen, Heidi M; Frystyk, Jan; Faber, Jens

    2012-01-01

    Aim a-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of a-defensins in CHF patients and healthy controls and to examine......% confidence interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed a-defensin values. The combination of high a-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure...... in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. a-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III-IV than in patients in NYHA class I-II and healthy controls (P = 0.001). The absolute increase...

  13. Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell Responses.

    Valeria de Turris

    Full Text Available Several pathogens have been described to enter host cells via cholesterol-enriched membrane lipid raft microdomains. We found that disruption of lipid rafts by the cholesterol-extracting agent methyl-β-cyclodextrin or by the cholesterol-binding antifungal drug Amphotericin B strongly impairs the uptake of the fungal pathogen Candida albicans by human monocytes, suggesting a role of raft microdomains in the phagocytosis of the fungus. Time lapse confocal imaging indicated that Dectin-1, the C-type lectin receptor that recognizes Candida albicans cell wall-associated β-glucan, is recruited to lipid rafts upon Candida albicans uptake by monocytes, supporting the notion that lipid rafts act as an entry platform. Interestingly disruption of lipid raft integrity and interference with fungus uptake do not alter cytokine production by monocytes in response to Candida albicans but drastically dampen fungus specific T cell response. In conclusion, these data suggest that monocyte lipid rafts play a crucial role in the innate and adaptive immune responses to Candida albicans in humans and highlight a new and unexpected immunomodulatory function of the antifungal drug Amphotericin B.

  14. Enteral nutrition in surgery

    Sucha, R.; Lichvarova, I.; Duchon, R.; Dolnik, J.; Pindak, D.

    2011-01-01

    Enteral feeding provides physiologic, metabolic, safety, and cost benefits over parenteral nutrition. There are various ways enteral nutritional is administered and scheduled. The method of administration must be individualized to each patient's specific needs. Enteral nutrition is not only the supply of exogenous substrates and to prevent depletion of endogenous sources. Today the enteral nutrition becomes part of a therapeutic strategy to influence the severity of the disease to affect the function of GIT, and to modulate immune responses of the gut and the whole organism. Early enteral nutrition in the postoperative period reduces the risk of infectious complications. (author)

  15. Babesial vector tick defensin against Babesia sp. parasites.

    Tsuji, Naotoshi; Battsetseg, Badgar; Boldbaatar, Damdinsuren; Miyoshi, Takeharu; Xuan, Xuenan; Oliver, James H; Fujisaki, Kozo

    2007-07-01

    Antimicrobial peptides are major components of host innate immunity, a well-conserved, evolutionarily ancient defensive mechanism. Infectious disease-bearing vector ticks are thought to possess specific defense molecules against the transmitted pathogens that have been acquired during their evolution. We found in the tick Haemaphysalis longicornis a novel parasiticidal peptide named longicin that may have evolved from a common ancestral peptide resembling spider and scorpion toxins. H. longicornis is the primary vector for Babesia sp. parasites in Japan. Longicin also displayed bactericidal and fungicidal properties that resemble those of defensin homologues from invertebrates and vertebrates. Longicin showed a remarkable ability to inhibit the proliferation of merozoites, an erythrocyte blood stage of equine Babesia equi, by killing the parasites. Longicin was localized at the surface of the Babesia sp. parasites, as demonstrated by confocal microscopic analysis. In an in vivo experiment, longicin induced significant reduction of parasitemia in animals infected with the zoonotic and murine B. microti. Moreover, RNA interference data demonstrated that endogenous longicin is able to directly kill the canine B. gibsoni, thus indicating that it may play a role in regulating the vectorial capacity in the vector tick H. longicornis. Theoretically, longicin may serve as a model for the development of chemotherapeutic compounds against tick-borne disease organisms.

  16. Gene organization of a novel defensin of Ixodes ricinus: first annotation of an intron/exon structure in a hard tick defensin gene and first evidence of the occurrence of two isoforms of one member of the arthropod defensin family

    Rudenko, Natalia; Golovchenko, Maryna; Grubhoffer, Libor

    2007-01-01

    Roč. 16, č. 4 (2007), s. 501-507 ISSN 0962-1075 R&D Projects: GA MŠk(CZ) LC06009; GA ČR(CZ) GA524/06/1479 Institutional research plan: CEZ:AV0Z60220518 Keywords : defensin * Ixodes ricinus * intron/exon structure * immune response * antimicrobial activity Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.787, year: 2007

  17. Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

    Sperling Rhoda

    2011-08-01

    Full Text Available Abstract Background During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. Methods We compare culture-generated monocyte derived DCs (MDDCs with directly isolated myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy. Results We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients. Conclusions Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

  18. Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

    Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

    2010-12-01

    Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

  19. The Alpha-defensin Test for Periprosthetic Joint Infections Is Not Affected by Prior Antibiotic Administration.

    Shahi, Alisina; Parvizi, Javad; Kazarian, Gregory S; Higuera, Carlos; Frangiamore, Salvatore; Bingham, Joshua; Beauchamp, Christopher; Valle, Craig Della; Deirmengian, Carl

    2016-07-01

    Previous studies have demonstrated that the administration of antibiotics to patients before performing diagnostic testing for periprosthetic joint infection (PJI) can interfere with the accuracy of test results. Although a single-institution study has suggested that alpha-defensin maintains its concentration and sensitivity even after antibiotic treatment, this has not yet been demonstrated in a larger multiinstitutional study. (1) For the evaluation of PJI, is prior antibiotic administration associated with decreased alpha-defensin levels? (2) When prior antibiotics are given, is alpha-defensin a better screening test for PJI than the traditional tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fluid white blood cells, fluid polymorphonuclear cells [PMNs], and fluid culture)? This retrospective study included data from 106 hip and knee arthroplasties with Musculoskeletal Infection Society-defined PJI from four centers. Of the 106 patients in this study, 30 (28%) were treated with antibiotics for PJI before diagnostic workup (ABX group), and 76 (72%) were not treated before the diagnostic workup (NO-ABX group). There were no differences in age, sex, joint, culture-negative rate, or bacteriology between groups. The patients in the ABX group had antibiotics initiated by physicians who commenced care before assessment for PJI by the treating surgeon's service. We compared the alpha-defensin levels and sensitivity between the ABX and NO-ABX groups. Additionally, the sensitivity of the alpha-defensin test was compared to that of traditional tests for PJI among patients on antibiotics. The administration of antibiotics before performing the alpha-defensin test for PJI was not associated with a decreased median alpha-defensin level (ABX group, median 4.2 [range, 1.79-12.8 S/CO] versus NO-ABX, median 4.9 [range, 0.5-16.8 S/CO], difference of medians: 0.68 S/CO [95% confidence interval {CI}, -0.98 to 1.26], p = 0.451). Furthermore, the alpha-defensin

  20. Immediate preoperative enteral nutrition (preoperative enteral nutrition

    Lađević Nebojša

    2017-01-01

    Full Text Available Nutritional support of surgical patients is a necessary part of the treatment. It alone cannot cure the disease but it significantly affects the recovery of patients and supports surgical interventions. Patients in malnutrition have shown to have significantly more postoperative infectious and non-infectious complications. This significantly prolongs treatment time and increases costs. However, there is one fact that cannot be expressed in money, which is the patient's impression of the surgical intervention. Adequate preoperative patient support, based on the intake of liquid nutritive solutions, reduces preoperative stress and deflects the metabolic response. Now, it is recommended for adults and children older than one year to drink clear liquid up to 2 hours before induction in anesthesia. Appropriate enteral nutrition has a significant place in the postoperative recovery of patients. Enteral nutrition is reducing complications, mainly infectious complications because the function of the digestive system as one large immune system is preserved. Perioperative enteral nutrition is a necessary part of the modern treatment of surgical patients. In addition to the significant effect on the occurrence of postoperative complications, it is also important that this type of diet improves the psychological status of patients.

  1. Comprehensive assessment of sequence variation within the copy number variable defensin cluster on 8p23 by target enriched in-depth 454 sequencing

    Zhang Xinmin

    2011-05-01

    Full Text Available Abstract Background In highly copy number variable (CNV regions such as the human defensin gene locus, comprehensive assessment of sequence variations is challenging. PCR approaches are practically restricted to tiny fractions, and next-generation sequencing (NGS approaches of whole individual genomes e.g. by the 1000 Genomes Project is confined by an affordable sequence depth. Combining target enrichment with NGS may represent a feasible approach. Results As a proof of principle, we enriched a ~850 kb section comprising the CNV defensin gene cluster DEFB, the invariable DEFA part and 11 control regions from two genomes by sequence capture and sequenced it by 454 technology. 6,651 differences to the human reference genome were found. Comparison to HapMap genotypes revealed sensitivities and specificities in the range of 94% to 99% for the identification of variations. Using error probabilities for rigorous filtering revealed 2,886 unique single nucleotide variations (SNVs including 358 putative novel ones. DEFB CN determinations by haplotype ratios were in agreement with alternative methods. Conclusion Although currently labor extensive and having high costs, target enriched NGS provides a powerful tool for the comprehensive assessment of SNVs in highly polymorphic CNV regions of individual genomes. Furthermore, it reveals considerable amounts of putative novel variations and simultaneously allows CN estimation.

  2. Thermal inactivation of enteric viruses and bioaccumulation of enteric foodborne viruses in live oysters (Crassostrea virginica)

    Human enteric viruses are one of the main causative agents of shellfish associated outbreaks. In this study, the kinetics of viral bioaccumulation in live oysters and the heat stability of the most predominant enteric viruses were determined in both tissue culture and in oyster tissues. A human nor...

  3. Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis.

    Aceti, Arianna; Gori, Davide; Barone, Giovanni; Callegari, Maria Luisa; Fantini, Maria Pia; Indrio, Flavia; Maggio, Luca; Meneghin, Fabio; Morelli, Lorenzo; Zuccotti, Gianvincenzo; Corvaglia, Luigi

    2016-07-30

    Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD -3.15 days (95% CI -5.25/-1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.

  4. Association of beta-Defensin Copy Number and Psoriasis in Three Cohorts of European Origin

    Stuart, P.E.; Huffmeier, U.; Nair, R.P.; Palla, R.; Tejasvi, T.; Schalkwijk, J.; Elder, J.T.; Reis, A.; Armour, J.A.

    2012-01-01

    A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study, we attempted to replicate that finding in larger new cohorts from Erlangen (N=2,017) and

  5. Proteinase 3 carries small unusual carbohydrates and associates with αlpha-defensins

    Zoega, Morten; Ravnsborg, Tina; Højrup, Peter

    2012-01-01

    with carbohydrates at Asn 102 and 147 carrying unusual small moieties indicating heavy processing. Mass spectrometric analysis and immuno blotting revealed strong association of highly purified PR3 with α-defensins and oligomers hereof. Irreversible inhibition of PR3 by α1-antitrypsin did not affect its association...

  6. Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II

    Schneider, Tanja; Kruse, Thomas; Wimmer, Reinhard

    2010-01-01

    Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show th...

  7. Antiplasmodial Activity Is an Ancient and Conserved Feature of Tick Defensins

    Cabezas Cruz, Alejandro; Tonk, M.; Bouchut, A.; Pierrot, C.; Pierce, R.J.; Kotsyfakis, Michalis; Rahnamaeian, M.; Vilcinskas, A.; Khalife, J.; Valdés, James J.

    2016-01-01

    Roč. 7, 24 October (2016), č. článku 1682. ISSN 1664-302X R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : ticks * defensins * antimicrobial spectrum * ancestral sequence reconstruction * Plasmodium falciparum Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.076, year: 2016

  8. Lucifensins, the Insect Defensins of Biomedical Importance: The Story behind Maggot Therapy

    Čeřovský, Václav; Bém, R.

    2014-01-01

    Roč. 7, č. 3 (2014), s. 251-264 ISSN 1424-8247 R&D Projects: GA ČR GA203/08/0536 Institutional support: RVO:61388963 Keywords : antimicrobial peptide * insect defensin * lucifensin * maggot therapy * Lucilia sericata * Lucilia cuprina * peptide isolation * peptide identification Subject RIV: CC - Organic Chemistry http://www.mdpi.com/1424-8247/7/3/251

  9. Tribolium castaneum defensins are primarily active against Gram-positive bacteria

    Tonk, M.; Knorr, E.; Cabezas-Cruz, A.; Valdés, James J.; Kollewe, C.; Vilcinskas, A.

    2015-01-01

    Roč. 132, NOV 2015 (2015), s. 208-215 ISSN 0022-2011 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : Antimicrobial peptides * Defensin * Innate immunity * Insects * Tribolium castaneum * Gram-positive bacteria Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.198, year: 2015

  10. Determination of beta-defensin genomic copy number in different populations

    Fode, Peder; Jespersgaard, Cathrine; Hardwick, Robert J

    2011-01-01

    There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and ß-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with...

  11. 1,25-Dihydroxyvitamin-D3 Induces Avian β-Defensin Gene Expression in Chickens.

    Long Zhang

    Full Text Available Host defense peptides (HDPs play a critical role in innate immunity. Specific modulation of endogenous HDP synthesis by dietary compounds has been regarded as a novel approach to boost immunity and disease resistance in animal production. 1,25-dihydroxy vitamin D3 (1,25D3 is well known as a powerful HDP inducer in humans, but limited information about the effect of 1,25D3 on HDPs in poultry is available. Here, we sought to examine whether 1,25D3 could stimulate avian β-defensin (AvBD expression in chickens. We used chicken embryo intestinal epithelial cells (CEIEPCs and peripheral blood mononuclear cells (PBMCs to study the effect of 1,25D3 on the expression of AvBDs. We observed that 1,25D3 is able to up-regulate the expression of several AvBDs in CEIEPCs and PBMCs, whereas it increased the amounts of AvBD4 mRNA in CEIEPCs only in the presence of lipopolysaccharide (LPS. On the other hand, LPS treatment not only inhibited the expression of CYP24A1 but also altered the expression pattern of VDR in CEIEPCs. Furthermore, AvBDs were not directly regulated by 1,25D3, as cycloheximide completely blocked 1,25D3-induced expression of AvBDs. Our observations suggest that 1,25D3 is capable of inducing AvBD gene expression and is a potential antibiotic alternative through augmentation of host innate immunity as well as disease control in chickens.

  12. Human Antimicrobial Peptides and Proteins

    Guangshun Wang

    2014-05-01

    Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

  13. OCCURRENCE OF ENTERIC VIRUSES IN SURFACE WATERS

    Human enteric viruses cause a number of diseases when individuals are exposed to contaminated drinking & recreational waters. Vaccination against poliovirus has virtually eliminated poliomyelitis from the planet. Other members of enterovirus group cause numerous diseases. Hepatit...

  14. Genetics of enteric neuropathies

    Brosens, Erwin; Burns, Alan J.; Brooks, Alice S.; Matera, Ivana; Borrego, Salud; Ceccherini, Isabella; Tam, Paul K.; García-Barceló, Maria-Mercè; Thapar, Nikhil; Benninga, Marc A.; Hofstra, Robert M. W.; Alves, Maria M.

    2016-01-01

    Abnormal development or disturbed functioning of the enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is associated with the development of neuropathic gastrointestinal motility disorders. Here, we review the underlying molecular basis of these disorders and

  15. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    Brinkman, Adam S.; Murali, Sangita G.; Hitt, Stacy; Solverson, Patrick M.; Holst, Jens J.

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg−1·day−1), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel

  16. Expression of BrD1, a plant defensin from Brassica rapa, confers resistance against brown planthopper (Nilaparvata lugens) in transgenic rices.

    Choi, Man-Soo; Kim, Yul-Ho; Park, Hyang-Mi; Seo, Bo-Yoon; Jung, Jin-Kyo; Kim, Sun-Tae; Kim, Min-Chul; Shin, Dong-Bum; Yun, Hong-Tai; Choi, Im-Soo; Kim, Chung-Kon; Lee, Jang-Yong

    2009-08-31

    Plant defensins are small (5-10 kDa) basic peptides thought to be an important component of the defense pathway against fungal and/or bacterial pathogens. To understand the role of plant defensins in protecting plants against the brown planthopper, a type of insect herbivore, we isolated the Brassica rapa Defensin 1 (BrD1) gene and introduced it into rice (Oryza sativa L.) to produce stable transgenic plants. The BrD1 protein is homologous to other plant defensins and contains both an N-terminal endoplasmic reticulum signal sequence and a defensin domain, which are highly conserved in all plant defensins. Based on a phylogenetic analysis of the defensin domain of various plant defensins, we established that BrD1 belongs to a distinct subgroup of plant defensins. Relative to the wild type, transgenic rices expressing BrD1 exhibit strong resistance to brown planthopper nymphs and female adults. These results suggest that BrD1 exhibits insecticidal activity, and might be useful for developing cereal crop plants resistant to sap-sucking insects, such as the brown planthopper.

  17. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

  18. Plant defensins and their potential use as pest control in agriculture

    Rojas Arias, Adriana Carolina; Zamora Espitia, Humberto Miguel

    2010-01-01

    Plants, as all organisms in nature, have elaborate systems of defense against pathogens; which can be physical or chemical and produced in a constitutive and induced way. Among the induced chemical barriers, there is a group of low molecular weight proteins, known as antimicrobial peptides (AMPs). These peptides include defensins, which are peptides with a molecular weight about 5 to 7 KDa, isoelectric point of 9, and length of about 45 to 55 amino acids. Likewise, they have the ability to avoid the growth of phytopathogenic microorganisms, mainly funguses. Moreover, these peptides create resistance to abiotic conditions of stress in plants. This manuscript seeks to make a clear and current description about the recent characteristics and researches related to plant defensins and their most significant uses in pathogens management in crops of economical relevance. It also intends to go deep into the study of such proteins in order to use them as a control strategy, such as production of transgenic plants and microorganisms.

  19. Transfer and expression of the rabbit defensin NP-1 gene in lettuce (Lactuca sativa).

    Song, D; Xiong, X; Tu, W F; Yao, W; Liang, H W; Chen, F J; He, Z Q

    2017-01-23

    Lettuce (Lactuca sativa L.) is an annual plant of the daisy family, Asteraceae, with high food and medicinal value. However, the crop is susceptible to several viruses that are transmitted by aphids and is highly vulnerable to post-harvest diseases, as well as insect and mammal pests and fungal and bacterial diseases. Here, the rabbit defensin gene NP-1 was transferred into lettuce by Agrobacterium-mediated transformation to obtain a broad-spectrum disease-resistant lettuce. Transgenic lettuce plants were selected and regenerated on selective media. The presence of the NP-1 gene in these plants was confirmed by western blot analyses. Resistance tests revealed native defensin NP-1 expression conferred partial resistance to Bacillus subtilis and Pseudomonas aeruginosa, which suggests new possibilities for lettuce disease resistance.

  20. The DUB/USP17 deubiquitinating enzymes: A gene family within a tandemly repeated sequence, is also embedded within the copy number variable Beta-defensin cluster

    Scott Christopher J

    2010-04-01

    Full Text Available Abstract Background The DUB/USP17 subfamily of deubiquitinating enzymes were originally identified as immediate early genes induced in response to cytokine stimulation in mice (DUB-1, DUB-1A, DUB-2, DUB-2A. Subsequently we have identified a number of human family members and shown that one of these (DUB-3 is also cytokine inducible. We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the 'CAAX' box protease RCE1. Results Here we demonstrate that the human DUB/USP17 family members are found on both chromosome 4p16.1, within a block of tandem repeats, and on chromosome 8p23.1, embedded within the copy number variable beta-defensin cluster. In addition, we show that the multiple genes observed in humans and other distantly related mammals have arisen due to the independent expansion of an ancestral sequence within each species. However, it is also apparent when sequences from humans and the more closely related chimpanzee are compared, that duplication events have taken place prior to these species separating. Conclusions The observation that the DUB/USP17 genes, which can influence cell growth and survival, have evolved from an unstable ancestral sequence which has undergone multiple and varied duplications in the species examined marks this as a unique family. In addition, their presence within the beta-defensin repeat raises the question whether they may contribute to the influence of this repeat on immune related conditions.

  1. Defensin from the ornate sheep tick Dermacentor marginatus and its effect on Lyme borreliosis spirochetes

    Chrudimská, Tereza; Čeřovský, Václav; Slaninová, Jiřina; Rego, Ryan O. M.; Grubhoffer, Libor

    2014-01-01

    Roč. 46, č. 2 (2014), s. 165-170 ISSN 0145-305X R&D Projects: GA ČR(CZ) GAP302/11/1901 Institutional support: RVO:60077344 ; RVO:61388963 Keywords : Tick * Dermacentor marginatus * Defensin * Borrelia afzelii * Antimicrobial activity * Peptide synthesis Subject RIV: EE - Microbiology, Virology; EE - Microbiology, Virology (UOCHB-X) Impact factor: 2.815, year: 2014

  2. A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro

    Zhengyang Zeng

    2016-04-01

    Full Text Available Hepatitis B virus (HBV infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC. Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel–modulating activities in the future.

  3. Identification and partial characterisation of new members of the Ixodes ricinus defensin family

    Tonk, Miray; Cabezas Cruz, Alejandro; Valdés, James J.; Rego, Ryan O. M.; Rudenko, Natalia; Golovchenko, Maryna; Bell-Sakyi, L.; de la Fuente, J.; Grubhoffer, Libor

    2014-01-01

    Roč. 540, č. 2 (2014), s. 146-152 ISSN 0378-1119 R&D Projects: GA ČR(CZ) GAP302/11/1901; GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : antimicrobial peptide * defensin * Ixodes ricinus * tick * tick cell line Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.138, year: 2014

  4. Heterologous expression and solution structure of defensin from lentil Lens culinaris

    Shenkarev, Zakhar O. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow (Russian Federation); Gizatullina, Albina K. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow (Russian Federation); Moscow Institute of Physics and Technology (State University), Department of Physicochemical Biology and Biotechnology, Institutskii per., 9, 141700 Dolgoprudny, Moscow Region (Russian Federation); Finkina, Ekaterina I.; Alekseeva, Ekaterina A.; Balandin, Sergey V.; Mineev, Konstantin S. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow (Russian Federation); Arseniev, Alexander S. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow (Russian Federation); Moscow Institute of Physics and Technology (State University), Department of Physicochemical Biology and Biotechnology, Institutskii per., 9, 141700 Dolgoprudny, Moscow Region (Russian Federation); Ovchinnikova, Tatiana V., E-mail: ovch@ibch.ru [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow (Russian Federation); Moscow Institute of Physics and Technology (State University), Department of Physicochemical Biology and Biotechnology, Institutskii per., 9, 141700 Dolgoprudny, Moscow Region (Russian Federation)

    2014-08-22

    Highlights: • Lentil defensin Lc-def and its {sup 15}N-labeled analog were overexpressed in E. coli. • Lc-def is active against fungi, but does not inhibit growth of G+ and G− bacteria. • Lc-def spatial structure involves triple-stranded β-sheet and α-helix (CSαβ motif). • Lc-def is able to bind to anionic lipid vesicles under low-salt conditions. • NMR data revealed significant μs–ms mobility in the loops 1 and 3 of Lc-def. - Abstract: A new defensin Lc-def, isolated from germinated seeds of the lentil Lens culinaris, has molecular mass 5440.4 Da and consists of 47 amino acid residues. Lc-def and its {sup 15}N-labeled analog were overexpressed in Escherichia coli. Antimicrobial activity of the recombinant protein was examined, and its spatial structure, dynamics, and interaction with lipid vesicles were studied by NMR spectroscopy. It was shown that Lc-def is active against fungi, but does not inhibit the growth of Gram-positive and Gram-negative bacteria. The peptide is monomeric in aqueous solution and contains one α-helix and triple-stranded β-sheet, which form cysteine-stabilized αβ motif (CSαβ) previously found in other plant defensins. The sterically neighboring loop1 and loop3 protrude from the defensin core and demonstrate significant mobility on the μs–ms timescale. Lc-def does not bind to the zwitterionic lipid (POPC) vesicles but interacts with the partially anionic (POPC/DOPG, 7:3) membranes under low-salt conditions. The Lc-def antifungal activity might be mediated through electrostatic interaction with anionic lipid components of fungal membranes.

  5. Heterologous expression and solution structure of defensin from lentil Lens culinaris

    Shenkarev, Zakhar O.; Gizatullina, Albina K.; Finkina, Ekaterina I.; Alekseeva, Ekaterina A.; Balandin, Sergey V.; Mineev, Konstantin S.; Arseniev, Alexander S.; Ovchinnikova, Tatiana V.

    2014-01-01

    Highlights: • Lentil defensin Lc-def and its 15 N-labeled analog were overexpressed in E. coli. • Lc-def is active against fungi, but does not inhibit growth of G+ and G− bacteria. • Lc-def spatial structure involves triple-stranded β-sheet and α-helix (CSαβ motif). • Lc-def is able to bind to anionic lipid vesicles under low-salt conditions. • NMR data revealed significant μs–ms mobility in the loops 1 and 3 of Lc-def. - Abstract: A new defensin Lc-def, isolated from germinated seeds of the lentil Lens culinaris, has molecular mass 5440.4 Da and consists of 47 amino acid residues. Lc-def and its 15 N-labeled analog were overexpressed in Escherichia coli. Antimicrobial activity of the recombinant protein was examined, and its spatial structure, dynamics, and interaction with lipid vesicles were studied by NMR spectroscopy. It was shown that Lc-def is active against fungi, but does not inhibit the growth of Gram-positive and Gram-negative bacteria. The peptide is monomeric in aqueous solution and contains one α-helix and triple-stranded β-sheet, which form cysteine-stabilized αβ motif (CSαβ) previously found in other plant defensins. The sterically neighboring loop1 and loop3 protrude from the defensin core and demonstrate significant mobility on the μs–ms timescale. Lc-def does not bind to the zwitterionic lipid (POPC) vesicles but interacts with the partially anionic (POPC/DOPG, 7:3) membranes under low-salt conditions. The Lc-def antifungal activity might be mediated through electrostatic interaction with anionic lipid components of fungal membranes

  6. Two novel antimicrobial defensins from rice identified by gene coexpression network analyses.

    Tantong, Supaluk; Pringsulaka, Onanong; Weerawanich, Kamonwan; Meeprasert, Arthitaya; Rungrotmongkol, Thanyada; Sarnthima, Rakrudee; Roytrakul, Sittiruk; Sirikantaramas, Supaart

    2016-10-01

    Defensins form an antimicrobial peptides (AMP) family, and have been widely studied in various plants because of their considerable inhibitory functions. However, their roles in rice (Oryza sativa L.) have not been characterized, even though rice is one of the most important staple crops that is susceptible to damaging infections. Additionally, a previous study identified 598 rice genes encoding cysteine-rich peptides, suggesting there are several uncharacterized AMPs in rice. We performed in silico gene expression and coexpression network analyses of all genes encoding defensin and defensin-like peptides, and determined that OsDEF7 and OsDEF8 are coexpressed with pathogen-responsive genes. Recombinant OsDEF7 and OsDEF8 could form homodimers. They inhibited the growth of the bacteria Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, and Erwinia carotovora subsp. atroseptica with minimum inhibitory concentration (MIC) ranging from 0.6 to 63μg/mL. However, these OsDEFs are weakly active against the phytopathogenic fungi Helminthosporium oryzae and Fusarium oxysporum f.sp. cubense. This study describes a useful method for identifying potential plant AMPs with biological activities. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Oil Palm Defensin: A Thermal Stable Peptide that Restricts the Mycelial Growth of Ganoderma boninense.

    Tan, Yung-Chie; Ang, Cheng-Liang; Wong, Mui-Yun; Ho, Chai-Ling

    2016-01-01

    Plant defensins are plant defence peptides that have many different biological activities, including antifungal, antimicrobial, and insecticidal activities. A cDNA (EgDFS) encoding defensin was isolated from Elaeis guineensis. The open reading frame of EgDFS contained 231 nucleotides encoding a 71-amino acid protein with a predicted molecular weight at 8.69 kDa, and a potential signal peptide. The eight highly conserved cysteine sites in plant defensins were also conserved in EgDFS. The EgDFS sequence lacking 30 amino acid residues at its N-terminus (EgDFSm) was cloned into Escherichia coli BL21 (DE3) pLysS and successfully expressed as a soluble recombinant protein. The recombinant EgDFSm was found to be a thermal stable peptide which demonstrated inhibitory activity against the growth of G. boninense possibly by inhibiting starch assimilation. The role of EgDFSm in oil palm defence system against the infection of pathogen G. boninense was discussed.

  8. An anionic defensin from Plutella xylostella with potential activity against Bacillus thuringiensis.

    Xu, X-X; Zhang, Y-Q; Freed, S; Yu, J; Gao, Y-F; Wang, S; Ouyang, L-N; Ju, W-Y; Jin, F-L

    2016-12-01

    Insect defensins, are cationic peptides that play an important role in immunity against microbial infection. In the present study, an anionic defensin from Plutella xylostella, (designated as PxDef) was first cloned and characterized. Amino acid sequence analysis showed that the mature peptide owned characteristic six-cysteine motifs with predicted isoelectric point of 5.57, indicating an anionic defensin. Quantitative real-time polymerase chain reaction analysis showed that PxDef was significantly induced in epidermis, fat body, midgut and hemocytes after injection of heat-inactivated Bacillus thuringiensis, while such an induction was delayed by the injection of live B. thuringiensis in the 4th instar larvae of P. xylostella. Knocking down the expression of nuclear transcription factor Dorsal in P. xylostella by RNA interference significantly decreased the mRNA level of PxDef, and increased the sensitivity of P. xylostella larvae to the infection by live B. thuringiensis. The purified recombinant mature peptide (PxDef) showed higher activity against Gram-positive bacteria, with the minimum inhibition concentrations of 1.6 and 2.6 µM against B. thuringiensis and Bacillus subtilis, respectively. To our knowledge, this is the first report about an anionic PxDef, which may play an important role in the immune system of P. xylostella against B. thuringiensis.

  9. Antibacterial activity and phospholipid recognition of the recombinant defensin J1-1 from Capsicum genus.

    Guillén-Chable, Francisco; Arenas-Sosa, Iván; Islas-Flores, Ignacio; Corzo, Gerardo; Martinez-Liu, Cynthia; Estrada, Georgina

    2017-08-01

    The gene of the four disulfide-bridged defensin J1-1 from Capsicum was cloned into the expression vector pQE30 containing a 6His-tag as fusion protein. This construct was transfected into Origami strain of Escherichia coli and expressed after induction with isopropyl thiogalactoside (IPTG). The level of expression was 4 mg/L of culture medium, and the His-tagged recombinant defensin (HisXarJ1-1) was expressed exclusively into inclusion bodies. After solubilization, HisXarJ1-1 was purified by affinity and hydrophobic interaction chromatography. The reverse-phase HPLC profile of the HisXarJ1-1 product obtained from the affinity chromatography step showed single main peptide fraction of molecular masses of 7050.6 Da and after treatment with DTT a single fraction of 7, 042.6 Da corresponding to the reduced peptide was observed. An in vitro folding step of the HisXarJ1-1 generated a distinct profile of oxidized forms of the peptide this oxidized peptide was capable of binding phosphatidic acid in vitro. Possible dimer and oligomer of HisXarJ1-1 were visible in gel electrophoresis and immunodetected with anti-His antibodies. Pure recombinant defensin HisXarJ1-1 exhibited antibacterial activity against Pseudomonas aeruginosa. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Alteration of the mode of antibacterial action of a defensin by the amino-terminal loop substitution

    Gao, Bin; Zhu, Shunyi

    2012-01-01

    Highlights: ► Al-M is an engineered fungal defensin with the n-loop of an insect defensin. ► Al-M adopts a native defensin-like structure with high antibacterial potency. ► Al-M kills bacteria through a membrane disruptive mechanism. ► This work sheds light on the functional evolution of CSαβ-type defensins. -- Abstract: Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs) are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt a conserved cysteine-stabilized α-helical and β-sheet (CSαβ) fold with a different amino-terminal loop (n-loop) size and diverse modes of antibacterial action. Although they both are identified as inhibitors of cell wall biosynthesis, only CITDs evolved membrane disruptive ability by peptide oligomerization to form pores. To understand how this occurred, we modified micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by substituting its n-loop with that of an insect-derived CITDs. After air oxidization, the synthetic hybrid defensin (termed Al-M) was structurally identified by circular dichroism (CD) and functionally evaluated by antibacterial and membrane permeability assays and electronic microscopic observation. Results showed that Al-M folded into a native-like defensin structure, as determined by its CD spectrum that is similar to that of micasin. Al-M was highly efficacious against the Gram-positive bacterium Bacillus megaterium with a lethal concentration of 1.76 μM. As expected, in contrast to micasin, Al-M killed the bacteria through a membrane disruptive mechanism of action. The alteration in modes of action supports a key role of the n-loop extension in assembling functional surface of CITDs for membrane disruption. Our work provides mechanical evidence for evolutionary relationship between AITDs and CITDs.

  11. Alteration of the mode of antibacterial action of a defensin by the amino-terminal loop substitution

    Gao, Bin [Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing (China); Zhu, Shunyi, E-mail: Zhusy@ioz.ac.cn [Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing (China)

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer Al-M is an engineered fungal defensin with the n-loop of an insect defensin. Black-Right-Pointing-Pointer Al-M adopts a native defensin-like structure with high antibacterial potency. Black-Right-Pointing-Pointer Al-M kills bacteria through a membrane disruptive mechanism. Black-Right-Pointing-Pointer This work sheds light on the functional evolution of CS{alpha}{beta}-type defensins. -- Abstract: Ancient invertebrate-type and classical insect-type defensins (AITDs and CITDs) are two groups of evolutionarily related antimicrobial peptides (AMPs) that adopt a conserved cysteine-stabilized {alpha}-helical and {beta}-sheet (CS{alpha}{beta}) fold with a different amino-terminal loop (n-loop) size and diverse modes of antibacterial action. Although they both are identified as inhibitors of cell wall biosynthesis, only CITDs evolved membrane disruptive ability by peptide oligomerization to form pores. To understand how this occurred, we modified micasin, a fungus-derived AITDs with a non-membrane disruptive mechanism, by substituting its n-loop with that of an insect-derived CITDs. After air oxidization, the synthetic hybrid defensin (termed Al-M) was structurally identified by circular dichroism (CD) and functionally evaluated by antibacterial and membrane permeability assays and electronic microscopic observation. Results showed that Al-M folded into a native-like defensin structure, as determined by its CD spectrum that is similar to that of micasin. Al-M was highly efficacious against the Gram-positive bacterium Bacillus megaterium with a lethal concentration of 1.76 {mu}M. As expected, in contrast to micasin, Al-M killed the bacteria through a membrane disruptive mechanism of action. The alteration in modes of action supports a key role of the n-loop extension in assembling functional surface of CITDs for membrane disruption. Our work provides mechanical evidence for evolutionary relationship between AITDs and CITDs.

  12. Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease.

    Manko, Anna; Motta, Jean-Paul; Cotton, James A; Feener, Troy; Oyeyemi, Ayodele; Vallance, Bruce A; Wallace, John L; Buret, Andre G

    2017-01-01

    Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections.

  13. Petunia floral defensins with unique prodomains as novel candidates for development of fusarium wilt resistance in transgenic banana plants.

    Siddhesh B Ghag

    Full Text Available Antimicrobial peptides are a potent group of defense active molecules that have been utilized in developing resistance against a multitude of plant pathogens. Floral defensins constitute a group of cysteine-rich peptides showing potent growth inhibition of pathogenic filamentous fungi especially Fusarium oxysporum in vitro. Full length genes coding for two Petunia floral defensins, PhDef1 and PhDef2 having unique C-terminal 31 and 27 amino acid long predicted prodomains, were overexpressed in transgenic banana plants using embryogenic cells as explants for Agrobacterium-mediated genetic transformation. High level constitutive expression of these defensins in elite banana cv. Rasthali led to significant resistance against infection of Fusarium oxysporum f. sp. cubense as shown by in vitro and ex vivo bioassay studies. Transgenic banana lines expressing either of the two defensins were clearly less chlorotic and had significantly less infestation and discoloration in the vital corm region of the plant as compared to untransformed controls. Transgenic banana plants expressing high level of full-length PhDef1 and PhDef2 were phenotypically normal and no stunting was observed. In conclusion, our results suggest that high-level constitutive expression of floral defensins having distinctive prodomains is an efficient strategy for development of fungal resistance in economically important fruit crops like banana.

  14. Do enteric neurons make hypocretin? ☆

    Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

    2008-01-01

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin. PMID:18191238

  15. Enteral nutrition - child - managing problems

    ... page: //medlineplus.gov/ency/patientinstructions/000164.htm Enteral nutrition - child - managing problems To use the sharing features ... trouble breathing, call 911. References Mcclave SA. Enteral nutrition. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  16. Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines.

    Weichert, Stefan; Jennewein, Stefan; Hüfner, Eric; Weiss, Christel; Borkowski, Julia; Putze, Johannes; Schroten, Horst

    2013-10-01

    Human milk oligosaccharides help to prevent infectious diseases in breastfed infants. Larger scale testing, particularly in animal models and human clinical studies, is still limited due to shortened availability of more complex oligosaccharides. The purpose of this study was to evaluate 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) synthesized by whole-cell biocatalysis for their biological activity in vitro. Therefore, we have tested these oligosaccharides for their inhibitory potential of pathogen adhesion in two different human epithelial cell lines. 2'-FL could inhibit adhesion of Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella enterica serovar fyris, and Pseudomonas aeruginosa to the intestinal human cell line Caco-2 (reduction of 26%, 18%, 12%, and 17%, respectively), as could be shown for 3-FL (enteropathogenic E coli 29%, P aeruginosa 26%). Furthermore, adherence of P aeruginosa to the human respiratory epithelial cell line A549 was significantly inhibited by 2'-FL and 3-FL (reduction of 24% and 23%, respectively). These results confirm the biological and functional activity of biotechnologically synthesized human milk oligosaccharides. Mass-tailored human milk oligosaccharides could be used in the future to supplement infant formula ingredients or as preventatives to reduce the impact of infectious diseases. © 2013 Elsevier Inc. All rights reserved.

  17. Voltage-gated potassium channel (K(v) 1) autoantibodies in patients with chagasic gut dysmotility and distribution of K(v) 1 channels in human enteric neuromusculature (autoantibodies in GI dysmotility).

    Hubball, A W; Lang, B; Souza, M A N; Curran, O D; Martin, J E; Knowles, C H

    2012-08-01

    Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs) was also investigated. Seventy-three patients were included in the study with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas' disease. Sera were screened for specific antibodies to glutamic acid decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic acetylcholine receptors (nAChRs; α3 subtype), and voltage-gated potassium channels (VGKCs, K(V) 1 subtype) using validated immunoprecipitation assays. The distribution of six VGKC subunits (K(V) 1.1-1.6), including those known to be antigenic targets of anti-VGKC antibodies was immunohistochemically investigated in all main human GI tract regions. Three patients (14%) with chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No antibodies were detected in patients with idiopathic GINMD. The VGKCs were found in enteric neurons at every level of the gut in unique yet overlapping distributions. The VGKC expression in GI smooth muscle was found to be limited to the esophagus. A small proportion of patients with GI dysfunction secondary to Chagas' disease have antibodies against VGKCs. The presence of these channels in the human enteric nervous system may have pathological relevance to the growing number of GINMDs with which anti-VGKC antibodies have been associated. © 2012 Blackwell Publishing Ltd.

  18. Tracing enteric viruses in the European berry fruit supply chain

    Maunula, L.; Kaupke, A.; Vasickova, P.; Soderberg, K.; Kozyra, I.; Lazic, S.; Poel, van der W.H.M.; Bouwknegt, M.; Rutjes, S.; Willems, K.A.; Moloney, R.; Agostino, D' M.; Husman, A.M.D.; Bonsdorff, C.H.; Rzezutka, A.; Pavlik, I.; Petrovic, T.; Cook, N.

    2013-01-01

    In recent years, numerous foodborne outbreaks due to consumption of berry fruit contaminated by human enteric viruses have been reported. This European multinational study investigated possible contamination routes by monitoring the entire food chain for a panel of human and animal enteric viruses.

  19. Spatio-Temporal Expression Patterns of Arabidopsis thaliana and Medicago truncatula Defensin-Like Genes

    Nallu, Sumitha; Wang, Lin; Botanga, Christopher J.; Gomez, S. Karen; Costa, Liliana M.; Harrison, Maria J.; Samac, Deborah A.; Glazebrook, Jane; Katagiri, Fumiaki; Gutierrez-Marcos, Jose F.; VandenBosch, Kathryn A.

    2013-01-01

    Plant genomes contain several hundred defensin-like (DEFL) genes that encode short cysteine-rich proteins resembling defensins, which are well known antimicrobial polypeptides. Little is known about the expression patterns or functions of many DEFLs because most were discovered recently and hence are not well represented on standard microarrays. We designed a custom Affymetrix chip consisting of probe sets for 317 and 684 DEFLs from Arabidopsis thaliana and Medicago truncatula, respectively for cataloging DEFL expression in a variety of plant organs at different developmental stages and during symbiotic and pathogenic associations. The microarray analysis provided evidence for the transcription of 71% and 90% of the DEFLs identified in Arabidopsis and Medicago, respectively, including many of the recently annotated DEFL genes that previously lacked expression information. Both model plants contain a subset of DEFLs specifically expressed in seeds or fruits. A few DEFLs, including some plant defensins, were significantly up-regulated in Arabidopsis leaves inoculated with Alternaria brassicicola or Pseudomonas syringae pathogens. Among these, some were dependent on jasmonic acid signaling or were associated with specific types of immune responses. There were notable differences in DEFL gene expression patterns between Arabidopsis and Medicago, as the majority of Arabidopsis DEFLs were expressed in inflorescences, while only a few exhibited root-enhanced expression. By contrast, Medicago DEFLs were most prominently expressed in nitrogen-fixing root nodules. Thus, our data document salient differences in DEFL temporal and spatial expression between Arabidopsis and Medicago, suggesting distinct signaling routes and distinct roles for these proteins in the two plant species. PMID:23527067

  20. Spatio-temporal expression patterns of Arabidopsis thaliana and Medicago truncatula defensin-like genes.

    Mesfin Tesfaye

    Full Text Available Plant genomes contain several hundred defensin-like (DEFL genes that encode short cysteine-rich proteins resembling defensins, which are well known antimicrobial polypeptides. Little is known about the expression patterns or functions of many DEFLs because most were discovered recently and hence are not well represented on standard microarrays. We designed a custom Affymetrix chip consisting of probe sets for 317 and 684 DEFLs from Arabidopsis thaliana and Medicago truncatula, respectively for cataloging DEFL expression in a variety of plant organs at different developmental stages and during symbiotic and pathogenic associations. The microarray analysis provided evidence for the transcription of 71% and 90% of the DEFLs identified in Arabidopsis and Medicago, respectively, including many of the recently annotated DEFL genes that previously lacked expression information. Both model plants contain a subset of DEFLs specifically expressed in seeds or fruits. A few DEFLs, including some plant defensins, were significantly up-regulated in Arabidopsis leaves inoculated with Alternaria brassicicola or Pseudomonas syringae pathogens. Among these, some were dependent on jasmonic acid signaling or were associated with specific types of immune responses. There were notable differences in DEFL gene expression patterns between Arabidopsis and Medicago, as the majority of Arabidopsis DEFLs were expressed in inflorescences, while only a few exhibited root-enhanced expression. By contrast, Medicago DEFLs were most prominently expressed in nitrogen-fixing root nodules. Thus, our data document salient differences in DEFL temporal and spatial expression between Arabidopsis and Medicago, suggesting distinct signaling routes and distinct roles for these proteins in the two plant species.

  1. Functional characterization of two defensin isoforms of the hard tick Ixodes ricinus

    Chrudimská, Tereza; Slaninová, Jiřina; Rudenko, Natalia; Růžek, Daniel; Grubhoffer, Libor

    2011-01-01

    Roč. 4, č. 1 (2011), e63 ISSN 1756-3305 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA206/09/1782; GA ČR GD206/09/H026; GA ČR(CZ) GAP302/11/1901 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z40550506 Keywords : defensin * antimicrobial compounds * Ixodes ricinus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.937, year: 2011

  2. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    Brinkman, Adam S; Murali, Sangita G; Hitt, Stacy

    2012-01-01

    human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral...

  3. Energy enters guilty plea

    Makhijani, A.

    1994-01-01

    This article discusses the history leading up to the admission from Energy Secretary Hazel O'Leary that the Energy Department had conducted secret, dangerous, and immoral experiments on the American people. The article describes some of the experimentation on human subjects, attempts to identify the rationale behind exposing human subjects to radiation, and discusses the lack of ethics displayed by the Energy Department in both its experimentation and in its analysis of results. 16 refs

  4. Occurrence of water-borne enteric viruses in two settlements based in Eastern Chad: analysis of hepatitis E virus, hepatitis A virus and human adenovirus in water sources.

    Guerrero-Latorre, Laura; Carratala, Anna; Rodriguez-Manzano, Jesus; Calgua, Byron; Hundesa, Ayalkibet; Girones, Rosina

    2011-09-01

    Hepatitis E virus (HEV) is a common cause of water-borne acute hepatitis in areas with poor sanitation. In 2004 an outbreak of HEV infection affected around 2,000 people in Eastern Chad (Dar Sila). This paper describes the decrease in the incidence of acute jaundice syndrome (AJS) from 2004 until 2009 when a mean incidence of 0.48 cases/1,000 people/year was recorded in the region. Outbreaks of AJS were identified in some of the camps in 2007 and 2008. Moreover, water samples from drinking water sources were screened for human adenoviruses considered as viral indicators and for hepatitis A virus and HEV. Screening of faecal samples from donkeys for HEV gave negative results. Some of the samples were also analysed for faecal coliforms showing values before disinfection treatment between 3 and >50 colony forming units per 100 mL. All water samples tested were negative for HEV and HAV; however, the presence of low levels of human adenoviruses in 4 out of 16 samples analysed indicates possible human faecal contamination of groundwater. Consequently, breakdowns in the treatment of drinking water and/or increased excretion of hepatitis viruses, which could be related to the arrival of a new population, could spread future outbreaks through drinking water.

  5. [Modular enteral nutrition in pediatrics].

    Murillo Sanchís, S; Prenafeta Ferré, M T; Sempere Luque, M D

    1991-01-01

    Modular Enteral Nutrition may be a substitute for Parenteral Nutrition in children with different pathologies. Study of 4 children with different pathologies selected from a group of 40 admitted to the Maternal-Childrens Hospital "Valle de Hebrón" in Barcelona, who received modular enteral nutrition. They were monitored on a daily basis by the Dietician Service. Modular enteral nutrition consists of modules of proteins, peptides, lipids, glucids and mineral salts-vitamins. 1.--Craneo-encephalic traumatisms with loss of consciousness, Feeding with a combination of parenteral nutrition and modular enteral nutrition for 7 days. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended and modular enteral nutrition alone used up to a total of 43 days. 2.--55% burns with 36 days of hyperproteic modular enteral nutrition together with normal feeding. A more rapid recovery was achieved with an increase in total proteins and albumin. 3.--Persistent diarrhoea with 31 days of modular enteral nutrition, 5 days on parenteral nutrition alone and 8 days on combined parenteral nutrition and modular enteral nutrition. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended. 4.--Mucoviscidosis with a total of 19 days on modular enteral nutrition, 12 of which were exclusively on modular enteral nutrition and 7 as a night supplement to normal feeding. We administered proteic intakes of up to 20% of the total calorific intake and in concentrations of up to 1.2 calories/ml of the final preparation, always with a good tolerance. Modular enteral nutrition can and should be used as a substitute for parenteral nutrition in children with different pathologies, thus preventing the complications inherent in parenteral nutrition.

  6. Microscopic enteritis: Bucharest consensus.

    Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo

    2015-03-07

    Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

  7. Association of β-defensin copy number and psoriasis in three cohorts of European origin.

    Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John A L

    2012-10-01

    A single previous study has demonstrated significant association of psoriasis with copy number of β-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study, we attempted to replicate that finding in larger new cohorts from Erlangen (N=2,017) and Michigan (N=5,412), using improved methods for β-defensin copy number determination based on the paralog ratio test, and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (P=5.5 × 10(-4), odds ratio (OR)=1.25). We also find that the association is replicated in 2,616 cases and 2,526 controls from Michigan, although at reduced significance (P=0.014), but not in new samples from Erlangen (1,396 cases and 621 controls, P=0.38). Meta-analysis across all cohorts suggests a nominally significant association (P=6.6 × 10(-3)/2 × 10(-4)) with an effect size (OR=1.081) much lower than found in the discovery study (OR=1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association.

  8. Antiprotozoan and Antiviral Activities of Non-Cytotoxic Truncated and Variant Analogues of Mussel Defensin

    Philippe Roch

    2004-01-01

    Full Text Available We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P efficiently killed Trypanosoma brucei (ID50 4–12 μM and Leishmania major (ID50 12–45 μM in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 μM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs contained in marine invertebrates.

  9. Anti-Legionella dumoffii Activity of Galleria mellonella Defensin and Apolipophorin III

    Małgorzata Cytryńska

    2012-12-01

    Full Text Available The gram-negative bacterium Legionella dumoffii is, beside Legionella pneumophila, an etiological agent of Legionnaires’ disease, an atypical form of pneumonia. The aim of this study was to determine the antimicrobial activity of Galleria mellonella defense polypeptides against L. dumoffii. The extract of immune hemolymph, containing a mixture of defense peptides and proteins, exhibited a dose-dependent bactericidal effect on L. dumoffii. The bacterium appeared sensitive to a main component of the hemolymph extract, apolipophorin III, as well as to a defense peptide, Galleria defensin, used at the concentrations 0.4 mg/mL and 40 μg/mL, respectively. L. dumoffii cells cultured in the presence of choline were more susceptible to both defense factors analyzed. A transmission electron microscopy study of bacterial cells demonstrated that Galleria defensin and apolipophorin III induced irreversible cell wall damage and strong intracellular alterations, i.e., increased vacuolization, cytoplasm condensation and the appearance of electron-white spaces in electron micrographs. Our findings suggest that insects, such as G. mellonella, with their great diversity of antimicrobial factors, can serve as a rich source of compounds for the testing of Legionella susceptibility to defense-related peptides and proteins.

  10. Association of β-defensin copy number and psoriasis in three cohorts of European origin

    Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John AL

    2012-01-01

    A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study we attempted to replicate that finding in larger new cohorts from Erlangen (N = 2017) and Michigan (N = 5412), using improved methods for beta-defensin copy number determination based on the paralog ratio test (PRT), and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (p = 5.5 × 10−4, OR = 1.25). We also find that the association is replicated in 2616 cases and 2526 controls from Michigan, although at reduced significance (p = 0.014), but not in new samples from Erlangen (1396 cases and 621 controls, p = 0.38). Meta-analysis across all cohorts suggests a nominally significant association (p = 6.6 × 10−3/2 × 10−4) with an effect size (OR = 1.081) much lower than found in the discovery study (OR = 1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association. PMID:22739795

  11. Eosinophils from patients with type 1 diabetes mellitus express high level of myeloid alpha-defensins and myeloperoxidase

    Neuwirth, Aleš; Dobeš, Jan; Oujezdská, Jana; Ballek, Ondřej; Benešová, Martina; Sumnik, Z.; Včeláková, J.; Koloušková, S.; Obermannová, B.; Kolář, Michal; Štechová, K.; Filipp, Dominik

    2012-01-01

    Roč. 273, č. 2 (2012), s. 158-163 ISSN 0008-8749 R&D Projects: GA MŠk 2B08066 Institutional research plan: CEZ:AV0Z50520514 Keywords : type 1 diabetes * alpha-defensin * myeloperoxidase * granulocyte * eosinophil Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.743, year: 2012

  12. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi

    Peter M. Dracatos

    2016-09-01

    Full Text Available Nicotiana alata defensins 1 and 2 (NaD1 and NaD2 are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An O-mannosyltransferase (pmt knockout (KO mutants (An∆pmtA, An∆pmtB, and An∆pmtC. An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol signalling knockout mutants from the cell wall integrity (CWI and high osmolarity glycerol (HOG mitogen-activated protein kinase (MAPK pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2.

  13. Pan-European monitoring of susceptibility to human-use antimicrobial agents in enteric bacteria isolated from healthy food-producing animals.

    de Jong, Anno; Thomas, Valérie; Simjee, Shabbir; Godinho, Kevin; Schiessl, Brigitte; Klein, Ulrich; Butty, Pascal; Vallé, Michel; Marion, Hervé; Shryock, Thomas R

    2012-03-01

    To determine the antimicrobial susceptibility of Escherichia coli, Salmonella, Campylobacter and Enterococcus from cattle, pigs and chickens across the European Union (EU) using uniform methodology. Intestinal samples (1624) were taken at slaughter across five EU countries. Bacteria were isolated in national laboratories, whilst MICs were determined in a central laboratory for key antimicrobials used in human medicine. Clinical resistance was based on CLSI breakpoints and decreased susceptibility based on European Food Safety Authority (EFSA)/EUCAST epidemiological cut-off values. Isolation rates were high for E. coli (n=1540), low for Salmonella (n=201) and intermediate for Campylobacter (n=940) and Enterococcus (n=786). For E. coli and Salmonella, clinical resistance to newer compounds (cefepime, cefotaxime and ciprofloxacin) was absent or low, but decreased susceptibility was apparent, particularly in chicken strains. Resistance to older compounds (except gentamicin) was variable and higher. Colistin resistance was absent for E. coli, but apparent for Salmonella. For Campylobacter jejuni, ciprofloxacin resistance was markedly prevalent for chickens, whereas clinical resistance and decreased susceptibility to erythromycin was absent or very low. For Campylobacter coli, resistance was notably higher. None of the Enterococcus faecium strains was resistant to linezolid, but some were resistant to ampicillin or vancomycin. Resistance to quinupristin/dalfopristin was frequent. Resistance patterns varied widely depending on bacterial species, antibiotics, hosts and region. Resistance varied among countries, particularly for older antimicrobials, but clinical resistance to newer antibiotics used to treat foodborne disease in humans was generally very low. In the absence of resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored.

  14. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

    2008-01-01

    Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm

  15. Determination of antimicrobial resistance to extended-spectrum cephalosporin, quinolones, and vancomycin in selected human enteric pathogens from Prince Edward Island, Canada.

    Awosile, Babafela; German, Gregory; Rodriguez-Lecompte, Juan Carlos; Saab, Matthew E; Heider, Luke C; McClure, J Trenton

    2018-04-05

    The aim of this study was to determine the frequency of fecal carriage of vancomycin-resistant Enterococcus spp. and Escherichia coli with reduced susceptibilities to extended-spectrum cephalosporins (ESCs) and quinolones in humans on Prince Edward Island, Canada. Convenience fecal samples from individuals on Prince Edward Island were screened phenotypically using selective culture and genotypically using multiplex polymerase chain reactions to detect E. coli and Enterococcus spp. resistant to critically important antimicrobials. Twenty-six (5.3%) of 489 individuals had E. coli with reduced susceptibility to ESCs. Twenty-five (96.2%) of the 26 isolates harbored bla TEM , 18 (69.2%) harbored bla CMY-2 , 16 (61.5%) harbored bla CTX-M groups, 2 (7.7%) harbored bla SHV genes. None of the ESC-resistant E. coli was positive for carbapenem resistance. Twenty-one (8.3%) of 253 individuals had E. coli isolates with reduced quinolone susceptibility. All 21 isolates were positive for at least 1 qnr gene, with 3 (14.3%) isolates positive for qnrB, 5 (23.8%) positive for qnrS, and 13 (61.9%) positive for both qnrB and qnrS genes. All the enterococci isolates were vancomycin-susceptible. Higher susceptibility to the critically important antimicrobials was found in this study. This study can serve as a baseline for future antimicrobial resistance surveillance within this region.

  16. The E7 oncoprotein of high-risk human papillomavirus type 16 enters the nucleus via a nonclassical Ran-dependent pathway

    Angeline, Michael; Merle, Eric; Moroianu, Junona

    2003-01-01

    E7, the major transforming protein of high-risk human papillomavirus (HPV), type 16, binds and inactivates the retinoblastoma protein (pRb), and the Rb-related proteins p107 and p130. HPV16 E7 is a nuclear protein lacking a classical basic nuclear localization signal. In this study we investigated the nuclear import of HPV16 E7 oncoprotein in digitonin-permeabilized HeLa cells. HPV16 E7 nuclear import was independent of pRb, as an E7 ΔDLYC variant defective in pRb binding was imported into the nuclei of digitonin-permeabilized cells as efficiently as wild-type E7 in the presence of exogenous cytosol. Interestingly, we discovered that HPV16 E7 is imported into the nuclei via a novel pathway different from those mediated by Kap α2β1 heterodimers, Kap β1, or Kap β2. Nuclear accumulation of E7 required Ran and was not inhibited by the RanG19V-GTP variant, an inhibitor of Kap β mediated import pathways. Together the data suggest that HPV16 E7 translocates through the nuclear pores via a nonclassical Ran-dependent pathway, independent of the main cytosolic Kap β import receptors

  17. Enter the Gripping Beast

    Sindbæk, Søren Michael

    2012-01-01

    on innovations. Mostly, however, the time-resolution of archaeological data is too coarse-grained to allow us to grasp this potential to the full. In the period c. AD 790-850 a distinctly new artistic motif, the Gripping Beast, emerged in Scandinavia. A series of narrowly dated contexts provide anchor points......, which allows us to chart this innovation process and to point out some of the locations where this development took place; the reception of the mew motif is traced in grave finds across Scandinavia. This allows us to follow an early medieval innovation through the human-material interactions of an actor-network....

  18. Enteral feeding without pancreatic stimulation

    Kaushik, Neeraj; Pietraszewski, Marie; Holst, Jens Juul

    2005-01-01

    OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result...

  19. Enteric-coated mycophenolate sodium.

    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  20. Diversification of defensins and NLRs in Arabidopsis species by different evolutionary mechanisms.

    Mondragón-Palomino, Mariana; Stam, Remco; John-Arputharaj, Ajay; Dresselhaus, Thomas

    2017-12-15

    Genes encoding proteins underlying host-pathogen co-evolution and which are selected for new resistance specificities frequently are under positive selection, a process that maintains diversity. Here, we tested the contribution of natural selection, recombination and transcriptional divergence to the evolutionary diversification of the plant defensins superfamily in three Arabidopsis species. The intracellular NOD-like receptor (NLR) family was used for comparison because positive selection has been well documented in its members. Similar to defensins, NLRs are encoded by a large and polymorphic gene family and many of their members are involved in the immune response. Gene trees of Arabidopsis defensins (DEFLs) show a high prevalence of clades containing orthologs. This indicates that their diversity dates back to a common ancestor and species-specific duplications did not significantly contribute to gene family expansion. DEFLs are characterized by a pervasive pattern of neutral evolution with infrequent positive and negative selection as well as recombination. In comparison, most NLR alignment groups are characterized by frequent occurrence of positive selection and recombination in their leucine-rich repeat (LRR) domain as well negative selection in their nucleotide-binding (NB-ARC) domain. While major NLR subgroups are expressed in pistils and leaves both in presence or absence of pathogen infection, the members of DEFL alignment groups are predominantly transcribed in pistils. Furthermore, conserved groups of NLRs and DEFLs are differentially expressed in response to Fusarium graminearum regardless of whether these genes are under positive selection or not. The present analyses of NLRs expands previous studies in Arabidopsis thaliana and highlights contrasting patterns of purifying and diversifying selection affecting different gene regions. DEFL genes show a different evolutionary trend, with fewer recombination events and significantly fewer instances of

  1. Diarrhea in enterally fed patients: blame the diet?

    Chang, Sue-Joan; Huang, Hsiu-Hua

    2013-09-01

    Diarrhea has great impact on enteral nutrition. The purpose of this review is to identify the factors leading to diarrhea during enteral nutrition and to provide the published updates on diarrhea prevention through nutritional intervention. Diarrhea in enteral fed patients is attributed to multiple factors, including medications (major contributor), infections, bacterial contamination, underlying disease, and enteral feeding. Diet management can alleviate diarrhea in enteral feeding. High content of fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAPs) in enteral formula is postulated to induce diarrhea and lower FODMAPs formula may reduce the likelihood of diarrhea in enterally fed patients. Fiber-enriched formula can reduce the incidence of diarrhea and produce short-chain fatty acids for colonocytes. Ingesting prebiotics, nonviable probiotics or probiotic derivatives, and human lactoferrin may provide alternatives for reducing/preventing diarrhea. Enteral feeding is not generally considered the primary cause of diarrhea, which is frequently linked to prescribed medications. When diarrhea is apparent, healthcare members should evaluate the possible risk factors and systematically attempt to eliminate the underlying causes of diarrhea before reducing or suspending enteral feeding. Lower FODMAPs formula, prebiotics, probiotic derivatives, and lactoferrin may be used to manage enteral feeding-related diarrhea.

  2. Combined enteral and parenteral nutrition.

    Wernerman, Jan

    2012-03-01

    To review and discuss the evidence and arguments to combine enteral nutrition and parenteral nutrition in the ICU, in particular with reference to the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The EPaNIC study shows an advantage in terms of discharges alive from the ICU when parenteral nutrition is delayed to day 8 as compared with combining enteral nutrition and parenteral nutrition from day 3 of ICU stay. The difference between the guidelines from the European Society of Enteral and Parenteral Nutrition in Europe and American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine in North America concerning the combination of enteral nutrition and parenteral nutrition during the initial week of ICU stay was reviewed. The EPaNIC study clearly demonstrates that early parenteral nutrition in the ICU is not in the best interests of most patients. Exactly at what time point the combination of enteral nutrition and parenteral nutrition should be considered is still an open question.

  3. Beta-defensins-2 expressions in gingival epithelium cells after probiotic Lactobacillus reuteri induction

    Tuti Kusumaningsih

    2016-12-01

    Full Text Available Background: Beta-defensins (BD are antimicrobial peptides that play a role in defense against pathogens. Beta-defensins (BD are expressed by a variety of epithelial cells, including gingival epithelium, salivary glands, saliva and salivary duct. BD-1 is expressed constitutively, while BD-2 and BD-3 expressions can be induced by commensal bacteria. Probiotics are commensal bacteria, thus L. reuteri as probiotic bacteria may act as “inducer” for BD-2 in epithelial gingiva. S. mutans is the main bacteria causing dental caries and sensitive to BD-2. Purpose: This study was aimed to prove that the administration of probiotic L. reuteri may improve BD-2 expressions in the gingiva epithelium. Method: This study was conducted in vivo using twenty-four male Rattus norvegicus Wistar strains aged 10-12 weeks and weighed 120-150 g. Those rats were randomly divided into four groups, namely negative control group (not induced with L. reuteri or S. mutans, positive control group (induced with S. mutans for 14 days, treatment group 1 (induced with L. reuteri for 14 days and S. mutans for 7 days, and treatment group 2 (induced with L. reuteri and S. mutans for 14 days concurrently. The concentration of L. reuteri used was 4x108cfu/ml, while the concentration of S. mutans was 1x 1010cfu/ml. 0.1 ml of each was dropped in the region of the mandibular incisors. BD-2 expression was calculated using immunohistochemical method. The difference of BD-2 expressions in gingival epithelial cells in the respective groups was analyzed by Anova/SPSS. Results: There were significant differences in BD-2 expressions in gingival epithelial cells in each group based on the results of Anova test (p=0.001. Conclusion: The administration of probiotic L. reuteri is able to increase BD-2 expressions in gingival epithelial cells.

  4. The increasing of beta-defensin-2 level in saliva after probiotic Lactobacillus reuteri administration

    Tuti Kusumaningsih

    2015-03-01

    Full Text Available Background: Commesal bacteria is an excellent inducer for beta defensin-2 (BD-2. Probiotics bacteria Lactobacillus reuteri (L. reuteri as commensal bacteria may play the same role as an excellent inducer for BD-2. Beta defensin is natural antimicrobial peptides widely expressed in oral cavity, including in epithelium salivary gland. Streptococcus mutans (S. mutans as the main of bacteria causing caries are sensitive to BD-2. Purpose: This research was aimed to determine whether administration of probiotic L. reuteri can increase salivary BD-2 level in Wistar rats. Methods: This research can be considered as a laboratory experimental research with a randomized control group post test only design. Twenty-four male Rattus norvegicus Wistar strain rats aged 3 months were used. They were randomly divided into four groups, namely two control groups (negative control group that was not induced and positive control group induced with S. mutans, and two treatment groups (K1: induced with L. reuteri for 14 days and S. mutans for 7 days, and K2: induced with L. reuteri and S. mutans simultaneously for 14 days. L. reuteri culture at a concentration of 108 CFU/ml and S. mutans culture at a concentration of 1010CFU/ml were induced into the oral cavity of Wistar rats. An examination of BD-2 level was then conducted by using Elisa techniques. results: There was significant difference of salivary BD-2 level among those treatment groups (p=0.001. BD-2 level in saliva was increased after the administration of L. reuteri. Conclusion: L. reuteri probiotic can increase salivary BD-2 level in Wistar rats.

  5. Enteric Methane Emission from Pigs

    Jørgensen, Henry; Theil, Peter Kappel; Knudsen, Knud Erik Bach

    2011-01-01

    per kg meat produced is increased (Fernández et al. 1983; Lekule et al. 1990). The present chapter will summarise our current knowledge concerning dietary and enteric fermentation that may influence the methane (CH4) emission in pigs. Enteric fermentation is the digestive process by which.......3 % of the worlds pig population. The main number of pigs is in Asia (59.6 %) where the main pig population stay in China (47.8 % of the worlds pig population). The objective of the chapter is therefore: To obtain a general overview of the pigs’ contribution to methane emission. Where is the pigs’ enteric gas...... produced and how is it measured. The variation in methane emission and factors affecting the emission. Possibility for reducing the enteric methane emission and the consequences....

  6. EARLY ENTERAL FEEDING AND DELAYED ENTERAL FEEDING- A COMPARATIVE STUDY

    Alli Muthiah

    2017-03-01

    Full Text Available BACKGROUND Nutrients form the fuel for the body, which comes in the form of carbohydrates, proteins and lipids. The body is intended to burn fuels in order to perform work. Starvation with malnutrition affects the postoperative patients and patients with acute pancreatitis. There is an increased risk of nosocomial infections and a delay in the wound healing may be noted. They are more prone for respiratory tract infections. Enteral Nutrition (EN delivers nutrition to the body through gastrointestinal tract. This also includes the oral feeding. This study will review the administration, rationale and assess the pros and cons associated with the early initiation of enteral feeding. The aim of this study is to evaluate if early commencement of enteral nutrition compared to traditional management (delayed enteral feeding is associated with fewer complications and improved outcome-  In patients undergoing elective/emergency gastrointestinal surgery.  In patients with acute pancreatitis. It is also used to determine whether a period of starvation (nil by mouth after gastrointestinal surgery or in the early days of acute pancreatitis is beneficial in terms of specific outcomes. MATERIALS AND METHODS A prospective cohort interventional study was conducted using 100 patients from July 2012 to November 2012. Patients satisfying the inclusion and exclusion criteria were included in the study. Patients admitted in my unit for GIT surgeries or acute pancreatitis constituted the test group, while patients admitted in other units for similar disease processes constituted the control group. RESULTS Our study concluded that early enteral feeding resulted in reduced incidence of surgical site infections. When the decreased length of stay, shorter convalescent period and the lesser post-interventional fatigue were taken into account, early enteral feeding has a definite cost benefit.CONCLUSION Early enteral feeding was beneficial associated with fewer

  7. The cold-induced defensin TAD1 confers resistance against snow mold and Fusarium head blight in transgenic wheat.

    Sasaki, Kentaro; Kuwabara, Chikako; Umeki, Natsuki; Fujioka, Mari; Saburi, Wataru; Matsui, Hirokazu; Abe, Fumitaka; Imai, Ryozo

    2016-06-20

    TAD1 (Triticum aestivum defensin 1) is induced during cold acclimation in winter wheat and encodes a plant defensin with antimicrobial activity. In this study, we demonstrated that recombinant TAD1 protein inhibits hyphal growth of the snow mold fungus, Typhula ishikariensis in vitro. Transgenic wheat plants overexpressing TAD1 were created and tested for resistance against T. ishikariensis. Leaf inoculation assays revealed that overexpression of TAD1 confers resistance against the snow mold. In addition, the TAD1-overexpressors showed resistance against Fusarium graminearum, which causes Fusarium head blight, a devastating disease in wheat and barley. These results indicate that TAD1 is a candidate gene to improve resistance against multiple fungal diseases in cereal crops. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity.

    Bailleul, Geoffrey; Kravtzoff, Amanda; Joulin-Giet, Alix; Lecaille, Fabien; Labas, Valérie; Meudal, Hervé; Loth, Karine; Teixeira-Gomes, Ana-Paula; Gilbert, Florence B; Coquet, Laurent; Jouenne, Thierry; Brömme, Dieter; Schouler, Catherine; Landon, Céline; Lalmanach, Gilles; Lalmanach, Anne-Christine

    2016-01-01

    Defensins are frontline peptides of mucosal immunity in the animal kingdom, including birds. Their resistance to proteolysis and their ensuing ability to maintain antimicrobial potential remains questionable and was therefore investigated. We have shown by bottom-up mass spectrometry analysis of protein extracts that both avian beta-defensins AvBD2 and AvBD7 were ubiquitously distributed along the chicken gut. Cathepsin B was found by immunoblotting in jejunum, ileum, caecum, and caecal tonsils, while cathepsins K, L, and S were merely identified in caecal tonsils. Hydrolysis product of AvBD2 and AvBD7 incubated with a panel of proteases was analysed by RP-HPLC, mass spectrometry and antimicrobial assays. AvBD2 and AvBD7 were resistant to serine proteases and to cathepsins D and H. Conversely cysteine cathepsins B, K, L, and S degraded AvBD2 and abolished its antibacterial activity. Only cathepsin K cleaved AvBD7 and released Ile4-AvBD7, a N-terminal truncated natural peptidoform of AvBD7 that displayed antibacterial activity. Besides the 3-stranded antiparallel beta-sheet typical of beta-defensins, structural analysis of AvBD7 by two-dimensional NMR spectroscopy highlighted the restricted accessibility of the C-terminus embedded by the N-terminal region and gave a formal evidence of a salt bridge (Asp9-Arg12) that could account for proteolysis resistance. The differential susceptibility of avian defensins to proteolysis opens intriguing questions about a distinctive role in the mucosal immunity against pathogen invasion.

  9. Purification, cDNA cloning and modification of a defensin from the coconut rhinoceros beetle, Oryctes rhinoceros.

    Ishibashi, J; Saido-Sakanaka, H; Yang, J; Sagisaka, A; Yamakawa, M

    1999-12-01

    A novel member of the insect defensins, a family of antibacterial peptides, was purified from larvae of the coconut rhinoceros beetle, Oryctes rhinoceros, immunized with Escherichia coli. A full-size cDNA was cloned by combining reverse-transcription PCR (RT-PCR), and 5'- and 3'-rapid amplification of cDNA ends (RACE). Analysis of the O. rhinoceros defensin gene expression showed it to be expressed in the fat body and hemocyte, midgut and Malpighian tubules. O. rhinoceros defensin showed strong antibacterial activity against Staphylococcus aureus. A 9-mer peptide amidated at its C-terminus, AHCLAICRK-NH2 (Ala22-Lys30-NH2), was synthesized based on the deduced amino-acid sequence, assumed to be an active site sequence by analogy with the sequence of a defensin isolated from larvae of the beetle Allomyrina dichotoma. This peptide showed antibacterial activity against S. aureus, methicillin-resistant S. aureus, E. coli and Pseudomonas aeruginosa. We further modified this oligopeptide and synthesized five 9-mer peptides, ALRLAIRKR-NH2, ALLLAIRKR-NH2, AWLLAIRKR-NH2, ALYLAIRKR-NH2 and ALWLAIRKR-NH2. These oligopeptides showed strong antibacterial activity against Gram-negative and Gram-positive bacteria. The antibacterial effect of Ala22-Lys30-NH2 analogues was due to its interaction with bacterial membranes, judging from the leakage of liposome-entrapped glucose. These Ala22-Lys30-NH2 analogues did not show haemolytic activity and did not inhibit the growth of murine fibroblast cells or macrophages, except for AWLLAIRKR-NH2.

  10. The enter-educate approach.

    Piotrow, P T; Coleman, P L

    1992-03-01

    This article describes how the Population Communication Services (PCS) has seized on the "enter-educate" approach, the blending of popular entertainment with social messages, to change reproductive health behavior. The enter-educate approach spreads its message through songs, soap operas, variety shows, and other types of popular entertainment mediums. Because they entertain, enter-educate projects can capture the attention of an audience -- such as young people -- who would otherwise scorn social messages. And the use of population mediums makes it possible to reach a variety of audiences. Funded by USAID, PCS began its first enter-educate project in response to the increasing number of teenage pregnancies in Latin America. PCS developed 2 songs and videos, which featured popular teenage singers to serve as role models, to urge abstinence. The songs became instant hits. Since then, PCS has mounted more then 80 major projects in some 40 countries. Highlights of programs range from a successful multi-media family planning campaign in Turkey to humorous television ads in Brazil promoting vasectomy. Recently, PCS initiated projects to teach AIDS awareness. At the core of the enter-educate approach is the social learning theory which holds that much behavior is learned through the observation of role-models. Health professionals work alongside entertainers to produce works that have audience appeal and factual social messages. The enter-educate approach works because it is popular, pervasive, personal, persuasive, and profitable. PCS has found that enter-educate programs pay for themselves through cost sharing and cost recovery.

  11. Microwave processing of honey negatively affects honey antibacterial activity by inactivation of bee-derived glucose oxidase and defensin-1.

    Bucekova, Marcela; Juricova, Valeria; Monton, Enrique; Martinotti, Simona; Ranzato, Elia; Majtan, Juraj

    2018-02-01

    Microwave (MW) thermal heating has been proposed as an efficient method for honey liquefaction, while maintaining honey quality criteria. However, little is known about the effects of MW thermal heating on honey antibacterial activity. In this study, we aimed to determine the effects of MW heating on the antibacterial activity of raw rapeseed honeys against Pseudomonas aeruginosa and Staphylococcus aureus, with a particular focus on two major bee-derived antibacterial components, defensin-1 and hydrogen peroxide (H 2 O 2 ). Our results demonstrated that MW thermal heating completely abolished honey antibacterial activity whereas conventional thermal treatment at 45 and 55°C did not affect the antibacterial activity of honey samples. A significant decrease in both glucose oxidase activity and H 2 O 2 production as well as defensin-1 amount was observed in MW-treated samples. Given that defensin-1 and H 2 O 2 are regular antibacterial components of all honeys, MW heating may have similar negative effects on every type of crystallized/liquid honey. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Partial deletion of chromosome 8 β-defensin cluster confers sperm dysfunction and infertility in male mice.

    Yu S Zhou

    2013-10-01

    Full Text Available β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9 in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility.

  13. Meat-based enteral nutrition

    Derevitskay, O. K.; Dydykin, A. S.

    2017-09-01

    Enteral nutrition is widely used in hospitals as a means of nutritional support and therapy for different diseases. Enteral nutrition must fulfil the energy needs of the body, be balanced by the nutrient composition and meet patient’s nutritional needs. Meat is a source of full-value animal protein, vitamins and minerals. On the basis of this research, recipes and technology for a meat-based enteral nutrition product were developed. The product is a ready-to-eat sterilised mixture in the form of a liquid homogeneous mass, which is of full value in terms of composition and enriched with vitamins and minerals, consists of particles with a size of not more than 0.3 mm and has the modified fat composition and rheological characteristics that are necessary for passage through enteral feeding tubes. The study presents experimental data on the content of the main macro- and micro-nutrients in the developed product. The new product is characterised by a balanced fatty acid composition, which plays an important role in correction of lipid metabolism disorders and protein-energy deficiency, and it is capable of satisfying patients’ daily requirements for vitamins and the main macro- and microelements when consuming 1500-2000 ml. Meat-based enteral nutrition can be used in diets as a standard mixture for effective correction of the energy and anabolic requirements of the body and support of the nutritional status of patients, including those with operated stomach syndrome.

  14. Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and ß-Defensins in Filaggrin-Deficient Skin Equivalents.

    Hönzke, Stefan; Wallmeyer, Leonie; Ostrowski, Anja; Radbruch, Moritz; Mundhenk, Lars; Schäfer-Korting, Monika; Hedtrich, Sarah

    2016-03-01

    Atopic dermatitis is a chronic skin condition with complex etiology. It is characterized by skin barrier defects and T helper type 2 (Th2)-polarized inflammation. Although mutations in the filaggrin gene are known to be prominent genetic risk factors for the development of atopic dermatitis, the interdependency between these and an altered cytokine milieu is not fully understood. In this study, we evaluated the direct effects of filaggrin deficiency on the cornified envelope, tight junction proteins, and innate immune response, and report the effects of Th2 cytokines in normal and filaggrin-deficient skin equivalents. Supplementation with IL-4 and IL-13 led to distinct histologic changes and significantly increased skin surface pH, both of which were enhanced in filaggrin knockdown skin equivalents. We detected a compensatory up-regulation of involucrin and occludin in filaggrin-deficient skin that was dramatically disturbed when simultaneous inflammation occurred. Furthermore, we found that a lack of filaggrin triggered an up-regulation of human ?-defensin 2 via an unknown mechanism, which was abolished by Th2 cytokine supplementation. Taken together, these results indicate that defects in the epidermal barrier, skin permeability, and cutaneous innate immune response are not primarily linked to filaggrin deficiency but are rather secondarily induced by Th2 inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Big defensins, a diverse family of antimicrobial peptides that follows different patterns of expression in hemocytes of the oyster Crassostrea gigas.

    Rosa, Rafael D; Santini, Adrien; Fievet, Julie; Bulet, Philippe; Destoumieux-Garzón, Delphine; Bachère, Evelyne

    2011-01-01

    Big defensin is an antimicrobial peptide composed of a highly hydrophobic N-terminal region and a cationic C-terminal region containing six cysteine residues involved in three internal disulfide bridges. While big defensin sequences have been reported in various mollusk species, few studies have been devoted to their sequence diversity, gene organization and their expression in response to microbial infections. Using the high-throughput Digital Gene Expression approach, we have identified in Crassostrea gigas oysters several sequences coding for big defensins induced in response to a Vibrio infection. We showed that the oyster big defensin family is composed of three members (named Cg-BigDef1, Cg-BigDef2 and Cg-BigDef3) that are encoded by distinct genomic sequences. All Cg-BigDefs contain a hydrophobic N-terminal domain and a cationic C-terminal domain that resembles vertebrate β-defensins. Both domains are encoded by separate exons. We found that big defensins form a group predominantly present in mollusks and closer to vertebrate defensins than to invertebrate and fungi CSαβ-containing defensins. Moreover, we showed that Cg-BigDefs are expressed in oyster hemocytes only and follow different patterns of gene expression. While Cg-BigDef3 is non-regulated, both Cg-BigDef1 and Cg-BigDef2 transcripts are strongly induced in response to bacterial challenge. Induction was dependent on pathogen associated molecular patterns but not damage-dependent. The inducibility of Cg-BigDef1 was confirmed by HPLC and mass spectrometry, since ions with a molecular mass compatible with mature Cg-BigDef1 (10.7 kDa) were present in immune-challenged oysters only. From our biochemical data, native Cg-BigDef1 would result from the elimination of a prepropeptide sequence and the cyclization of the resulting N-terminal glutamine residue into a pyroglutamic acid. We provide here the first report showing that big defensins form a family of antimicrobial peptides diverse not only in terms

  16. Big Defensins, a Diverse Family of Antimicrobial Peptides That Follows Different Patterns of Expression in Hemocytes of the Oyster Crassostrea gigas

    Rosa, Rafael D.; Santini, Adrien; Fievet, Julie; Bulet, Philippe; Destoumieux-Garzón, Delphine; Bachère, Evelyne

    2011-01-01

    Background Big defensin is an antimicrobial peptide composed of a highly hydrophobic N-terminal region and a cationic C-terminal region containing six cysteine residues involved in three internal disulfide bridges. While big defensin sequences have been reported in various mollusk species, few studies have been devoted to their sequence diversity, gene organization and their expression in response to microbial infections. Findings Using the high-throughput Digital Gene Expression approach, we have identified in Crassostrea gigas oysters several sequences coding for big defensins induced in response to a Vibrio infection. We showed that the oyster big defensin family is composed of three members (named Cg-BigDef1, Cg-BigDef2 and Cg-BigDef3) that are encoded by distinct genomic sequences. All Cg-BigDefs contain a hydrophobic N-terminal domain and a cationic C-terminal domain that resembles vertebrate β-defensins. Both domains are encoded by separate exons. We found that big defensins form a group predominantly present in mollusks and closer to vertebrate defensins than to invertebrate and fungi CSαβ-containing defensins. Moreover, we showed that Cg-BigDefs are expressed in oyster hemocytes only and follow different patterns of gene expression. While Cg-BigDef3 is non-regulated, both Cg-BigDef1 and Cg-BigDef2 transcripts are strongly induced in response to bacterial challenge. Induction was dependent on pathogen associated molecular patterns but not damage-dependent. The inducibility of Cg-BigDef1 was confirmed by HPLC and mass spectrometry, since ions with a molecular mass compatible with mature Cg-BigDef1 (10.7 kDa) were present in immune-challenged oysters only. From our biochemical data, native Cg-BigDef1 would result from the elimination of a prepropeptide sequence and the cyclization of the resulting N-terminal glutamine residue into a pyroglutamic acid. Conclusions We provide here the first report showing that big defensins form a family of antimicrobial

  17. Big defensins, a diverse family of antimicrobial peptides that follows different patterns of expression in hemocytes of the oyster Crassostrea gigas.

    Rafael D Rosa

    Full Text Available BACKGROUND: Big defensin is an antimicrobial peptide composed of a highly hydrophobic N-terminal region and a cationic C-terminal region containing six cysteine residues involved in three internal disulfide bridges. While big defensin sequences have been reported in various mollusk species, few studies have been devoted to their sequence diversity, gene organization and their expression in response to microbial infections. FINDINGS: Using the high-throughput Digital Gene Expression approach, we have identified in Crassostrea gigas oysters several sequences coding for big defensins induced in response to a Vibrio infection. We showed that the oyster big defensin family is composed of three members (named Cg-BigDef1, Cg-BigDef2 and Cg-BigDef3 that are encoded by distinct genomic sequences. All Cg-BigDefs contain a hydrophobic N-terminal domain and a cationic C-terminal domain that resembles vertebrate β-defensins. Both domains are encoded by separate exons. We found that big defensins form a group predominantly present in mollusks and closer to vertebrate defensins than to invertebrate and fungi CSαβ-containing defensins. Moreover, we showed that Cg-BigDefs are expressed in oyster hemocytes only and follow different patterns of gene expression. While Cg-BigDef3 is non-regulated, both Cg-BigDef1 and Cg-BigDef2 transcripts are strongly induced in response to bacterial challenge. Induction was dependent on pathogen associated molecular patterns but not damage-dependent. The inducibility of Cg-BigDef1 was confirmed by HPLC and mass spectrometry, since ions with a molecular mass compatible with mature Cg-BigDef1 (10.7 kDa were present in immune-challenged oysters only. From our biochemical data, native Cg-BigDef1 would result from the elimination of a prepropeptide sequence and the cyclization of the resulting N-terminal glutamine residue into a pyroglutamic acid. CONCLUSIONS: We provide here the first report showing that big defensins form a family

  18. Expression of beta-defensins pBD-1 and pBD-2 along the small tract of the pig: Lack of upregulation in vivo upon Salmonella typhimurium infection

    Veldhuizen, E.J.; Dijk, van A.; Tersteeg, M.H.; Kalkhove, S.I.; Meulen, van der J.; Niewold, T.A.; Haagsman, H.P.

    2007-01-01

    Defensins are antimicrobial peptides that play an important role in the innate immune response in the intestine. Up to date, only one ß-defensin (pBD-1), has been described in pig, which was found to be expressed at low levels in the intestine. We set-up a quantitative PCR method to detect the gene

  19. Correlation of levels of alpha-defensins determined by HPLC-ESI-MS in bronchoalveolar lavage fluid with the diagnosis of pneumonia in premature neonates.

    Tirone, Chiara; Boccacci, Simona; Inzitari, Rosanna; Tana, Milena; Aurilia, Claudia; Fanali, Chiara; Cabras, Tiziana; Messana, Irene; Castagnola, Massimo; Romagnoli, Costantino; Vento, Giovanni

    2010-08-01

    The presence of alpha-defensins in bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm newborns with gestational age (GA) groups: pneumonia group of nine neonates suffering from pulmonary infection (GA: 26.1 +/- 2.1 wk; birth weight: 787.4 +/- 309.9 g), with or without associated bloodstream infection, and nonpneumonia group of 15 neonates (GA: 27.7 +/- 2.0 wk; birth weight: 1019.0 +/- 319.8 g). BALF culture was positive for CONS (n = 5), Staphylococcus aureus (n = 1), and Candida spp (n = 3). BALF samples were analyzed by HPLC-electrospray Ionization-mass spectrometer. The alpha-defensins 1-4 concentration, absolute and differential white cells count were measured. Relative amounts of alpha-defensins 1-4 and the absolute number of neutrophils were found significantly higher in the pneumonia group with respect to the nonpneumonia group (p < 0.05). Moreover, positive significant correlations between the number of neutrophils and the alpha-defensins 1-3 levels were observed. In conclusion, our data show that preterm newborns, also at the lower GA, are able to produce alpha-defensins, underlining that their innate defense system is already active before the at-term delivery date.

  20. Nutrición enteral

    Barrachina Bellés, Lidón; García Hernández, Misericordia; Oto Cavero, Isabel

    1984-01-01

    Este trabajo nos introduce en la administración de la nutrición enteral, haciendo una revisión de los aspectos a tener en cuenta tanto en sus indicaciones, vias, tipos, métodos, cuidados y complicaciones más importantes.

  1. [Enteral nutrition in burn patients].

    Pereira, J L; Garrido, M; Gómez-Cía, T; Serrera, J L; Franco, A; Pumar, A; Relimpio, F; Astorga, R; García-Luna, P P

    1992-01-01

    Nutritional support plays an important role in the treatment of patients with burns. Due to the severe hypercatabolism that develops in these patients, oral support is insufficient in most cases, and this makes it essential to initiate artificial nutritional support (either enteral or parenteral). Enteral nutrition is more physiological than parenteral, and data exist which show that in patients with burns, enteral nutrition exercises a protective effect on the intestine and may even reduce the hypermetabolic response in these patients. The purpose of the study was to evaluate the effectiveness and tolerance of enteral nutritional support with a hypercaloric, hyperproteic diet with a high content of branched amino acids in the nutritional support of patients suffering from burns. The study included 12 patients (8 males and 4 females), admitted to the Burns Unit. Average age was 35 +/- 17 years (range: 21-85 years). The percentage of body surface affected by the burns was 10% in two cases, between 10-30% in three cases, between 30-50% in five cases and over 50% in two cases. Initiation of the enteral nutrition was between twenty-four hours and seven days after the burn. The patients were kept in the unit until they were discharged, and the average time spent in the unit was 31.5 days (range: 17-63 days). Total energetic requirements were calculated based on Harris-Benedict, with a variable aggression factor depending on the body surface burned, which varied from 2,000 and 4,000 cal day. Nitrogenous balance was determined on a daily basis, and plasmatic levels of total proteins, albumin and prealbumin on a weekly basis. There was a significant difference between the prealbumin values at the initiation and finalization of the enteral nutrition (9.6 +/- 2.24 mg/dl compared with 19.75 +/- 5.48 mg/dl; p diet was very good, and only mild complications such as diarrhoea developed in two patients. Enteral nutrition is a suitable nutritional support method for patients with

  2. Epigenetic regulation of enteric neurotransmission by gut bacteria.

    Tor eSavidge

    2016-01-01

    Full Text Available The Human Microbiome Project defined microbial community interactions with the human host, and provided important molecular insight into how epigenetic factors can influence intestinal ecosystems. Given physiological context, changes in gut microbial community structure are increasingly found to associate with alterations in enteric neurotransmission and disease. At present, it is not known whether shifts in microbial community dynamics represent cause or consequence of disease pathogenesis. The discovery of bacterial-derived neurotransmitters suggests further studies are needed to establish their role in enteric neuropathy. This mini-review highlights recent advances in bacterial communications to the autonomic nervous system and discusses emerging epigenetic data showing that diet, probiotic and antibiotic use may regulate enteric neurotransmission through modulation of microbial communities. Because of its limited scope, a particular emphasis is placed on bacterial regulation of enteric nervous system function in the intestine.

  3. CERN openlab enters fifth phase

    Andrew Purcell

    2015-01-01

    CERN openlab is a unique public-private partnership between CERN and leading ICT companies. At the start of this year, openlab officially entered its fifth phase, which will run until the end of 2017. For the first time in its history, it has extended beyond the CERN community to include other major European and international research laboratories.   Founded in 2001 to develop the innovative ICT systems needed to cope with the unprecedented computing challenges of the LHC, CERN openlab unites science and industry at the cutting edge of research and innovation. In a white paper published last year, CERN openlab set out the main ICT challenges it will tackle during its fifth phase, namely data acquisition, computing platforms, data storage architectures, computer management and provisioning, networks and connectivity, and data analytics. As it enters its fifth phase, CERN openlab is expanding to include other research laboratories. "Today, research centres in other disciplines are also st...

  4. Surgical treatment of radiation enteritis

    Cross, M.J.; Frazee, R.C. (Department of General Surgery, Scott and White Memorial Hospital, Temple TX (United States))

    1992-02-01

    Radiation enteritis is a progressive, disease process that causes intestinal fibrosis and obliterative endarteritis, which results in significant morbidity and mortality. The authors' clinical experience involving 20 patients over a 22-year period from 1967 through 1989 who underwent various surgical procedures to alleviate chronic symptoms secondary to radiation enteritis is described. Eight men and 12 women with a mean age of 52 years (24 to 81 years) underwent a total of 27 procedures for complications of radiation enteritis. Radiation therapy was delivered for treatment of gynecologic malignancies (55%), colorectal cancer (20%), prostate malignancies (10%), and others (15%). The mean average dose of radiation delivered was 5,514 rads with a range of 2,613 to 7,000 rads. The interval from radiation treatment to time of surgery averaged 9 years. Operative procedures consisted of 12 resection and primary anastomosis procedures and 15 resections with stoma creation. Formation of a stoma was used in patients with more severe disease. The 30-day operative mortality was 0% and morbidity was 55%. There were no anastomotic leaks or intra-abdominal abscesses. The authors conclude that resection and primary anastomosis can safely be performed in selected patients but that judicious use of stoma formation can avoid major mortality and morbidity associated with surgery in this setting.

  5. Surgical treatment of radiation enteritis

    Cross, M.J.; Frazee, R.C.

    1992-01-01

    Radiation enteritis is a progressive, disease process that causes intestinal fibrosis and obliterative endarteritis, which results in significant morbidity and mortality. The authors' clinical experience involving 20 patients over a 22-year period from 1967 through 1989 who underwent various surgical procedures to alleviate chronic symptoms secondary to radiation enteritis is described. Eight men and 12 women with a mean age of 52 years (24 to 81 years) underwent a total of 27 procedures for complications of radiation enteritis. Radiation therapy was delivered for treatment of gynecologic malignancies (55%), colorectal cancer (20%), prostate malignancies (10%), and others (15%). The mean average dose of radiation delivered was 5,514 rads with a range of 2,613 to 7,000 rads. The interval from radiation treatment to time of surgery averaged 9 years. Operative procedures consisted of 12 resection and primary anastomosis procedures and 15 resections with stoma creation. Formation of a stoma was used in patients with more severe disease. The 30-day operative mortality was 0% and morbidity was 55%. There were no anastomotic leaks or intra-abdominal abscesses. The authors conclude that resection and primary anastomosis can safely be performed in selected patients but that judicious use of stoma formation can avoid major mortality and morbidity associated with surgery in this setting

  6. The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection

    Wyatt, M.C.; Beswick, A.D.; Kunutsor, S.K.; Wilson, M.J.; Whitehouse, M.R.; Blom, A.W.

    2016-01-01

    Background: Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria. Methods: We performed a systematic review to identify diagnostic technique studies evaluating the accuracy of alpha-defensin or leukocyte esterase in the diagnosis of PJI. MEDLINE and Embase on Ovid, ACM, ADS, arXiv, CERN DS (Conseil Européen pour la Recherche Nucléaire Document Server), CrossRef DOI (Digital Object Identifier), DBLP (Digital Bibliography & Library Project), Espacenet, Google Scholar, Gutenberg, HighWire, IEEE Xplore (Institute of Electrical and Electronics Engineers digital library), INSPIRE, JSTOR (Journal Storage), OAlster (Open Archives Initiative Protocol for Metadata Harvesting), Open Content, Pubget, PubMed, and Web of Science were searched for appropriate studies indexed from inception until May 30, 2015, along with unpublished or gray literature. The classification of studies and data extraction were performed independently by 2 reviewers. Data extraction permitted meta-analysis of sensitivity and specificity with construction of receiver operating characteristic curves for each test. Results: We included 11 eligible studies. The pooled diagnostic sensitivity and specificity of alpha-defensin (6 studies) for PJI were 1.00 (95% confidence interval [CI], 0.82 to 1.00) and 0.96 (95% CI, 0.89 to 0.99), respectively. The area under the curve (AUC) for alpha-defensin and PJI was 0.99 (95% CI, 0.98 to 1.00). The pooled diagnostic sensitivity and specificity of leukocyte esterase (5 studies) for PJI were 0.81 (95% CI, 0.49 to 0.95) and 0.97 (95% CI, 0.82 to 0.99), respectively. The AUC for leukocyte esterase and PJI

  7. Overexpression of a defensin enhances resistance to a fruit-specific anthracnose fungus in pepper.

    Hyo-Hyoun Seo

    Full Text Available Functional characterization of a defensin, J1-1, was conducted to evaluate its biotechnological potentiality in transgenic pepper plants against the causal agent of anthracnose disease, Colletotrichum gloeosporioides. To determine antifungal activity, J1-1 recombinant protein was generated and tested for the activity against C. gloeosporioides, resulting in 50% inhibition of fungal growth at a protein concentration of 0.1 mg·mL-1. To develop transgenic pepper plants resistant to anthracnose disease, J1-1 cDNA under the control of 35S promoter was introduced into pepper via Agrobacterium-mediated genetic transformation method. Southern and Northern blot analyses confirmed that a single copy of the transgene in selected transgenic plants was normally expressed and also stably transmitted to subsequent generations. The insertion of T-DNA was further analyzed in three independent homozygous lines using inverse PCR, and confirmed the integration of transgene in non-coding region of genomic DNA. Immunoblot results showed that the level of J1-1 proteins, which was not normally accumulated in unripe fruits, accumulated high in transgenic plants but appeared to differ among transgenic lines. Moreover, the expression of jasmonic acid-biosynthetic genes and pathogenesis-related genes were up-regulated in the transgenic lines, which is co-related with the resistance of J1-1 transgenic plants to anthracnose disease. Consequently, the constitutive expression of J1-1 in transgenic pepper plants provided strong resistance to the anthracnose fungus that was associated with highly reduced lesion formation and fungal colonization. These results implied the significance of the antifungal protein, J1-1, as a useful agronomic trait to control fungal disease.

  8. Overexpression of a defensin enhances resistance to a fruit-specific anthracnose fungus in pepper.

    Seo, Hyo-Hyoun; Park, Sangkyu; Park, Soomin; Oh, Byung-Jun; Back, Kyoungwhan; Han, Oksoo; Kim, Jeong-Il; Kim, Young Soon

    2014-01-01

    Functional characterization of a defensin, J1-1, was conducted to evaluate its biotechnological potentiality in transgenic pepper plants against the causal agent of anthracnose disease, Colletotrichum gloeosporioides. To determine antifungal activity, J1-1 recombinant protein was generated and tested for the activity against C. gloeosporioides, resulting in 50% inhibition of fungal growth at a protein concentration of 0.1 mg·mL-1. To develop transgenic pepper plants resistant to anthracnose disease, J1-1 cDNA under the control of 35S promoter was introduced into pepper via Agrobacterium-mediated genetic transformation method. Southern and Northern blot analyses confirmed that a single copy of the transgene in selected transgenic plants was normally expressed and also stably transmitted to subsequent generations. The insertion of T-DNA was further analyzed in three independent homozygous lines using inverse PCR, and confirmed the integration of transgene in non-coding region of genomic DNA. Immunoblot results showed that the level of J1-1 proteins, which was not normally accumulated in unripe fruits, accumulated high in transgenic plants but appeared to differ among transgenic lines. Moreover, the expression of jasmonic acid-biosynthetic genes and pathogenesis-related genes were up-regulated in the transgenic lines, which is co-related with the resistance of J1-1 transgenic plants to anthracnose disease. Consequently, the constitutive expression of J1-1 in transgenic pepper plants provided strong resistance to the anthracnose fungus that was associated with highly reduced lesion formation and fungal colonization. These results implied the significance of the antifungal protein, J1-1, as a useful agronomic trait to control fungal disease.

  9. Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

    Haorile Chagan-Yasutan

    2016-09-01

    Full Text Available Leptospirosis is a zoonotic disease whose severe forms are often accompanied by kidney dysfunction. In the present study, urinary markers were studied for potential prediction of disease severity. Urine samples from 135 patients with or without leptospirosis at San Lazaro Hospital, the Philippines, were analyzed. Urine levels of defensin α1 (uDA1 were compared with those of neutrophil gelatinase-associated lipocalin (uNGAL and N-acetyl-β-d-glucosidase (uNAG. Serum creatinine (Cr was used as a marker of kidney injury. The levels of uDA1/Cr, uNGAL/Cr, and uNAG/Cr were positive in 46%, 90%, and 80% of leptospirosis patients, and 69%, 70%, and 70% of non-leptospirosis patients, respectively. In leptospirosis patients, the correlation of uDA1/Cr, uNGAL/Cr and uNAG/Cr levels with serum Cr were r = 0.3 (p < 0.01, r = 0.29 (p < 0.01, and r = 0.02 (p = 0.81, respectively. uDA1/Cr levels were correlated with uNGAL/Cr levels (r = 0.49, p < 0.01 and uNAG/Cr levels (r = 0.47, p < 0.0001 in leptospirosis patients. These findings suggest that uDA1, uNGAL, and uNAG were elevated in leptospirosis patients and reflected various types of kidney damage. uDA1 and uNGAL can be used to track kidney injury in leptospirosis patients because of their correlation with the serum Cr level.

  10. Enteral Feeding Set Handling Techniques.

    Lyman, Beth; Williams, Maria; Sollazzo, Janet; Hayden, Ashley; Hensley, Pam; Dai, Hongying; Roberts, Cristine

    2017-04-01

    Enteral nutrition therapy is common practice in pediatric clinical settings. Often patients will receive a pump-assisted bolus feeding over 30 minutes several times per day using the same enteral feeding set (EFS). This study aims to determine the safest and most efficacious way to handle the EFS between feedings. Three EFS handling techniques were compared through simulation for bacterial growth, nursing time, and supply costs: (1) rinsing the EFS with sterile water after each feeding, (2) refrigerating the EFS between feedings, and (3) using a ready-to-hang (RTH) product maintained at room temperature. Cultures were obtained at baseline, hour 12, and hour 21 of the 24-hour cycle. A time-in-motion analysis was conducted and reported in average number of seconds to complete each procedure. Supply costs were inventoried for 1 month comparing the actual usage to our estimated usage. Of 1080 cultures obtained, the overall bacterial growth rate was 8.7%. The rinse and refrigeration techniques displayed similar bacterial growth (11.4% vs 10.3%, P = .63). The RTH technique displayed the least bacterial growth of any method (4.4%, P = .002). The time analysis in minutes showed the rinse method was the most time-consuming (44.8 ± 2.7) vs refrigeration (35.8 ± 2.6) and RTH (31.08 ± 0.6) ( P refrigerating the EFS between uses is the next most efficacious method for handling the EFS between bolus feeds.

  11. Enteric neurons show a primary cilium.

    Luesma, Ma José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia-Verdugo, José Manuel; Junquera, Concepción

    2013-01-01

    The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  12. Expression of a radish defensin in transgenic wheat confers increased resistance to Fusarium graminearum and Rhizoctonia cerealis.

    Li, Zhao; Zhou, Miaoping; Zhang, Zengyan; Ren, Lijuan; Du, Lipu; Zhang, Boqiao; Xu, Huijun; Xin, Zhiyong

    2011-03-01

    Fusarium head blight (scab), primarily caused by Fusarium graminearum, is a devastating disease of wheat (Triticum aestivum L.) worldwide. Wheat sharp eyespot, mainly caused by Rhizoctonia cerealis, is one of the major diseases of wheat in China. The defensin RsAFP2, a small cyteine-rich antifungal protein from radish (Raphanus sativus), was shown to inhibit growth in vitro of agronomically important fungal pathogens, such as F. graminearum and R. cerealis. The RsAFP2 gene was transformed into Chinese wheat variety Yangmai 12 via biolistic bombardment to assess the effectiveness of the defensin in protecting wheat from the fungal pathogens in multiple locations and years. The genomic PCR and Southern blot analyses indicated that RsAFP2 was integrated into the genomes of the transgenic wheat lines and heritable. RT-PCR and Western blot proved that the RsAFP2 was expressed in these transgenic wheat lines. Disease tests showed that four RsAFP2 transgenic lines (RA1-RA4) displayed enhanced resistance to F. graminearum compared to the untransformed Yangmai 12 and the null-segregated plants. Assays on Q-RT-PCR and disease severity showed that the express level of RsAFP2 was associated with the enhanced resistance degree. Two of these transgenic lines (RA1 and RA2) also exhibited enhanced resistance to R. cerealis. These results indicated that the expression of RsAFP2 conferred increased resistance to F. graminearum and R. cerealis in transgenic wheat.

  13. A study on β-defensin-2 and histatin-5 as a diagnostic marker of early childhood caries progression

    Anna Jurczak

    2015-01-01

    Full Text Available BACKGROUND: Recently, a continuous growth of interest has been observed in antimicrobial peptides (AMPs in the light of an alarming increase in resistance of bacteria and fungi against antibiotics. AMPs are used as biomarkers in diagnosis and monitoring of oral cavity pathologies. Therefore, the determination of specific protein profiles in children diagnosed with early childhood caries (ECC might be a basis for effective screening tests and specialized examinations which may enable progression of disease METHODS: The objective of the studies was to determine the role of histatin-5 and β-defensing-2 as a diagnostic marker of early childhood caries progression. In this work, results of concentration determination of two salivary proteins (histatin-5 and β-defensin-2 were presented. In addition, bacterial profiles from dental plaque in various stages of ECC and control were marked. The assessment of alteration in the concentration of these two proteins in a study group of children with various stages of ECC and a control group consisting of children with no symptoms was performed by enzyme-linked immunosorbent assays RESULTS: The statistical analysis showed a significant increase in the concentration of histatin-5 and β-defensin-2 in the study group compared to the control group and correlated with the progression of the disease CONCLUSIONS: The confirmation of concentration changes in these proteins during the progression of dental caries may discover valuable disease progression biomarkers

  14. The β-defensin gallinacin-6 is expressed in the chicken digestive tract and has antimicrobial activity against food-borne pathogens

    van Dijk, A.; Veldhuizen, E.J.A.; Kalkhove, S.I.C.; Tjeerdsma-van Bokhoven, J.L.M.; Romijn, R.A.; Haagsman, H.P.

    2007-01-01

    Food-borne pathogens are responsible for most cases of food poisoning in developed countries and are often associated with poultry products, including chicken. Little is known about the role of ß-defensins in the chicken digestive tract and their efficacy. In this study, the expression of chicken

  15. The Arabidopsis mutant iop1 exhibits induced over-expression of the plant defensin gene PDF1.2 and enhanced pathogen resistance

    Penninckx, I.A.M.A.; Eggermont, K.; Schenk, P.M.; Ackerveken, van den G.; Cammue, B.P.A.; Thomma, B.P.H.J.

    2003-01-01

    Jasmonate and ethylene are concomitantly involved in the induction of the Arabidopsis plant defensin gene PDF1.2. To define genes in the signal transduction pathway leading to the induction of PDF1.2, we screened for mutants with induced over-expression of a β-glucuronidase reporter, under the

  16. A Map Enters the Conversation

    Munk, Anders Kristian

    Over the past decade STS scholars have been engaged in a continuous dialogue about the performativity of their methods and the interventions of their research practices. A frequently posed question is how STS can make a difference to its fields of study, what John Law has called its different...... 'modes of mattering'. In this paper I explore what difference digital cartography can make to STS practice. I draw on three examples from my own work where digitally mediated maps have entered the conversation and made critical, often surprising, differences to the research process. In my first example...... the map is brought along as an ethnographic device on a piece of fieldwork, in my second example it serves as the central collaborative object in a participatory design project, and in my third example the map becomes the object of contestation as it finds itself centre stage in the controversy...

  17. Advantages of enteral nutrition over parenteral nutrition

    Seres, David S.; Valcarcel, Monika; Guillaume, Alexandra

    2013-01-01

    It is a strong and commonly held belief among nutrition clinicians that enteral nutrition is preferable to parenteral nutrition. We provide a narrative review of more recent studies and technical reviews comparing enteral nutrition with parenteral nutrition. Despite significant weaknesses in the existing data, current literature continues to support the use of enteral nutrition in patients requiring nutrition support, over parenteral nutrition.

  18. CERN openlab enters new phase

    Katarina Anthony

    2012-01-01

    The newest phase of CERN’s openlab framework was inaugurated this week during a meeting of the openlab partners. This phase will last three years and will bring together existing openlab partners and a new contributor: Huawei.   Group picture taken at the first CERN openlab IV annual Board of Sponsors meeting, in the presence of the CERN Director-General, the partners and the openlab team members. © Fons Rademakers (CERN Photo Club). Eleven years ago, the creation of the CERN openlab created a long-term link between industrial partners and the Organization. Its framework has allowed industry to carry out large-scale IT research and development in an open atmosphere – an “Open Lab”, if you will. For CERN, openlab has contributed to giving the computing centre and, more broadly, the LHC community, the opportunity to ensure that the next generation of services and products is suitable to their needs. Now entering its fourth phase, openlab will ...

  19. Regulation of gene expression for defensins and lipid transfer protein in Scots pine seedlings by necrotrophic pathogen Alternaria alternata (Fr.

    Hrunyk Nataliya

    2017-06-01

    Full Text Available Damping-off disease in pine seedling, caused by fungi and oomycetes (Fusarium, Alternaria, Botrytis, Phytophthora and other species, is one of the most dangerous diseases in conifer nurseries and greenhouses worldwide. Alternaria alternata is a necrotrophic pathogen, which causes early blight in higher plants and results in massive economic losses in agro-industry as well as in forestry. Pine seedlings that lack strong lignificated and suberized cell walls at early stages of their growth are vulnerable to damping-off disease. So, triggering the synthesis of antimicrobial compounds, such as phytoalexins, anticipins and pathogenesis-related (PR proteins, is the main defense strategy to confine pathogens at early stages of pine ontogenesis. Defensins and lipid transfer proteins are members of two PR-protein families (PR-12 and PR-14 respectively and possess antimicrobial activities in vitro through contact toxicity, and the involvement in defense signalling. In this work, we describe the changes in the expression levels of four defensin genes and lipid transfer protein in Scots pine seedlings infected with A. alternata. The expression levels of PsDef1 and PsDef2 increased at 48 h.p.i. (hours post inoculation. The levels of PsDef4 transcripts have increased after 6 and 24 hours. Notably, at 48 h.p.i., the level of PsDef4 transcripts was decreased by 1.2 times compared to control. The level of PsDef3 transcripts was reduced at all three time points. On the other hand, the level of PsLTP1 transcripts increased at 6 h and 48 h.p.i.; while at 24 h.p.i., it decreased by 20% when compared to the control sample. Our results suggest that defensins and lipid transfer protein are involved in the defense response of young Scots pine to necrotrophic pathogen. Thus, those genes can be used as the molecular markers in forestry selection and development of the ecologically friendly remedies for coniferous seedlings cultivation in greenhouses and nurseries.

  20. Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

    Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

    2016-03-04

    Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance.

  1. Innate immune defences in the human endometrium

    Kelly Rodney W

    2003-11-01

    Full Text Available Abstract The human endometrium is an important site of innate immune defence, giving protection against uterine infection. Such protection is critical to successful implantation and pregnancy. Infection is a major cause of preterm birth and can also cause infertility and ectopic pregnancy. Natural anti-microbial peptides are key mediators of the innate immune system. These peptides, between them, have anti-bacterial, anti-fungal and anti-viral activity and are expressed at epithelial surfaces throughout the female genital tract. Two families of natural anti-microbials, the defensins and the whey acidic protein (WAP motif proteins, appear to be prominent in endometrium. The human endometrial epithelium expresses beta-defensins 1–4 and the WAP motif protein, secretory leukocyte protease inhibitor. Each beta-defensin has a different expression profile in relation to the stage of the menstrual cycle, providing potential protection throughout the cycle. Secretory leukocyte protease inhibitor is expressed during the secretory phase of the cycle and has a range of possible roles including anti-protease and anti-microbial activity as well as having effects on epithelial cell growth. The leukocyte populations in the endometrium are also a source of anti-microbial production. Neutrophils are a particularly rich source of alpha-defensins, lactoferrin, lysozyme and the WAP motif protein, elafin. The presence of neutrophils during menstruation will enhance anti-microbial protection at a time when the epithelial barrier is disrupted. Several other anti-microbials including the natural killer cell product, granulysin, are likely to have a role in endometrium. The sequential production of natural anti-microbial peptides by the endometrium throughout the menstrual cycle and at other sites in the female genital tract will offer protection from many pathogens, including those that are sexually transmitted.

  2. The Antifungal Plant Defensin HsAFP1 Is a Phosphatidic Acid-Interacting Peptide Inducing Membrane Permeabilization

    Tanne L. Cools

    2017-11-01

    Full Text Available HsAFP1, a plant defensin isolated from coral bells (Heuchera sanguinea, is characterized by broad-spectrum antifungal activity. Previous studies indicated that HsAFP1 binds to specific fungal membrane components, which had hitherto not been identified, and induces mitochondrial dysfunction and cell membrane permeabilization. In this study, we show that HsAFP1 reversibly interacts with the membrane phospholipid phosphatidic acid (PA, which is a precursor for the biosynthesis of other phospholipids, and to a lesser extent with various phosphatidyl inositol phosphates (PtdInsP’s. Moreover, via reverse ELISA assays we identified two basic amino acids in HsAFP1, namely histidine at position 32 and arginine at position 52, as well as the phosphate group in PA as important features enabling this interaction. Using a HsAFP1 variant, lacking both amino acids (HsAFP1[H32A][R52A], we showed that, as compared to the native peptide, the ability of this variant to bind to PA and PtdInsP’s is reduced (≥74% and the antifungal activity of the variant is reduced (≥2-fold, highlighting the link between PA/PtdInsP binding and antifungal activity. Using fluorescently labelled HsAFP1 in confocal microscopy and flow cytometry assays, we showed that HsAFP1 accumulates at the cell surface of yeast cells with intact membranes, most notably at the buds and septa. The resulting HsAFP1-induced membrane permeabilization is likely to occur after HsAFP1’s internalization. These data provide novel mechanistic insights in the mode of action of the HsAFP1 plant defensin.

  3. Transcriptional profiling avian beta-defensins in chicken oviduct epithelial cells before and after infection with Salmonella enterica serovar Enteritidis

    Bailey R Hartford

    2009-07-01

    Full Text Available Abstract Background Salmonella enterica serovar Enteritidis (SE colonizes the ovary and oviduct of chickens without causing overt clinical signs which can lead to SE-contamination of the content and membrane of shell-eggs as well as hatchery eggs. The organism utilizes the Salmonella Pathogenicity Island-2 encoded type III secretion system (T3SS-2 to promote persistence in the oviduct of laying hens. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR was carried out to determine the expression profiles of 14 known avian beta defensins (AvBDs in primary chicken oviduct epithelial cells (COEC before and after infections with a wild type SE strain and T3SS mutant SE strains carrying an inactivated sipA or pipB gene. Results Based on the expression levels in uninfected COEC, AvBDs can be loosely grouped into three categories with AvBD4-5 and AvBD9-12 being constitutively expressed at high levels; AvBD1, AvBD3, and AvBD13-14 at moderate levels; and AvBD2 and AvBD6-8 at minimal levels. Infection with the wild type SE strain temporarily repressed certain highly expressed AvBDs and induced the expression of minimally expressed AvBDs. The pipB mutant, compared to the wild type strain, had reduced suppressive effect on the expression of highly expressed AvBDs. Moreover, the pipB mutant elicited significantly higher levels of the minimally expressed AvBDs than the wild type SE or the sipA mutant did. Conclusion Chicken oviduct epithelial cells express most of the known AvBD genes in response to SE infection. PipB, a T3SS-2 effector protein, plays a role in dampening the β-defensin arm of innate immunity during SE invasion of chicken oviduct epithelium.

  4. Transcriptional profiling avian beta-defensins in chicken oviduct epithelial cells before and after infection with Salmonella enterica serovar Enteritidis.

    Ebers, Katie L; Zhang, C Yan; Zhang, M Zhenyu; Bailey, R Hartford; Zhang, Shuping

    2009-07-30

    Salmonella enterica serovar Enteritidis (SE) colonizes the ovary and oviduct of chickens without causing overt clinical signs which can lead to SE-contamination of the content and membrane of shell-eggs as well as hatchery eggs. The organism utilizes the Salmonella Pathogenicity Island-2 encoded type III secretion system (T3SS-2) to promote persistence in the oviduct of laying hens. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to determine the expression profiles of 14 known avian beta defensins (AvBDs) in primary chicken oviduct epithelial cells (COEC) before and after infections with a wild type SE strain and T3SS mutant SE strains carrying an inactivated sipA or pipB gene. Based on the expression levels in uninfected COEC, AvBDs can be loosely grouped into three categories with AvBD4-5 and AvBD9-12 being constitutively expressed at high levels; AvBD1, AvBD3, and AvBD13-14 at moderate levels; and AvBD2 and AvBD6-8 at minimal levels. Infection with the wild type SE strain temporarily repressed certain highly expressed AvBDs and induced the expression of minimally expressed AvBDs. The pipB mutant, compared to the wild type strain, had reduced suppressive effect on the expression of highly expressed AvBDs. Moreover, the pipB mutant elicited significantly higher levels of the minimally expressed AvBDs than the wild type SE or the sipA mutant did. Chicken oviduct epithelial cells express most of the known AvBD genes in response to SE infection. PipB, a T3SS-2 effector protein, plays a role in dampening the beta-defensin arm of innate immunity during SE invasion of chicken oviduct epithelium.

  5. Enteric hyperoxaluria in chronic pancreatitis.

    Demoulin, Nathalie; Issa, Zaina; Crott, Ralph; Morelle, Johann; Danse, Etienne; Wallemacq, Pierre; Jadoul, Michel; Deprez, Pierre H

    2017-05-01

    Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid

  6. Enteral Nutrition and Acute Pancreatitis: A Review

    Spanier, B. W. M.; Bruno, M. J.; Mathus-Vliegen, E. M. H.

    2011-01-01

    Introduction. In patients with acute pancreatitis (AP), nutritional support is required if normal food cannot be tolerated within several days. Enteral nutrition is preferred over parenteral nutrition. We reviewed the literature about enteral nutrition in AP. Methods. A MEDLINE search of the English

  7. Understanding and controlling the enteric nervous system

    Boeckxstaens, G. E.

    2002-01-01

    The enteric nervous system or the `Little Brain' of the gut controls gastrointestinal motility and secretion, and is involved in visceral sensation. In this chapter, new developments in understanding the function of the enteric nervous system are described. In particular, the interaction of this

  8. Noncommunicating Isolated Enteric Duplication Cyst in the ...

    Noncommunicating isolated enteric duplications in the abdomen are an extremely rare variant of enteric duplications with their own blood supply. We report a case of a noncommunicating isolated ileal duplication in a 10-month-old boy. He was admitted because of severe abdominal distension and developed irritability ...

  9. The expression of cytokines and β -defensin 2, - 3, -4 in rabbit bone tissue after hydroxyapatite (HAp), α- Tricalcium phosphate (α-TCP) and polymethylmethacrylate (PMMA) implantation

    Vamze, J; Pilmane, M; Skagers, A

    2012-01-01

    Bone loss induced by inflammation is one of the complications after biomaterial implantation. There is no much data on expression of cytokines and defensins into the bone tissue around the implants in literature. The aim of this work was to investigate the distribution and appearance of interleukin (IL)-1, IL-6, IL-8, IL-10 and (β - defensin (BD)-2, BD-3, BD-4 after the implantation of different biomaterials. Bone developing zones, signs of bone-implant contact and low expression of pro-inflammatory cytokine IL-1, IL-6 and anti-inflammatory cytokine IL-10 in experimental tissue with pure HAp and unburned HAp implants indicate a potential advantage of this material in terms of its biocompatibility over the other materials used in our study.

  10. Enteric neurospheres are not specific to neural crest cultures : Implications for neural stem cell therapies

    Binder, E. (Ellen); D. Natarajan (Dipa); J.E. Cooper (Julie E.); Kronfli, R. (Rania); Cananzi, M. (Mara); J.-M. Delalande (Jean-Marie); C. Mccann; A.J. Burns (Alan); N. Thapar (Nikhil)

    2015-01-01

    textabstractObjectives Enteric neural stem cells provide hope of curative treatment for enteric neuropathies. Current protocols for their harvesting from humans focus on the generation of 'neurospheres' from cultures of dissociated gut tissue. The study aims to better understand the derivation,

  11. The mycorrhiza-dependent defensin MtDefMd1 of Medicago truncatula acts during the late restructuring stages of arbuscule-containing cells.

    Marian Uhe

    Full Text Available Different symbiotic and pathogenic plant-microbe interactions involve the production of cysteine-rich antimicrobial defensins. In Medicago truncatula, the expression of four MtDefMd genes, encoding arbuscular mycorrhiza-dependent defensins containing an N-terminal signal peptide and exhibiting some differences to non-symbiotic defensins, raised over the time of fungal colonization. Whereas the MtDefMd1 and MtDefMd2 promoters were inactive in cells containing young arbuscules, cells with fully developed arbuscules displayed different levels of promoter activities, indicating an up-regulation towards later stages of arbuscule formation. MtDefMd1 and MtDefMd2 expression was absent or strongly down-regulated in mycorrhized ram1-1 and pt4-2 mutants, known for defects in arbuscule branching or premature arbuscule degeneration, respectively. A ~97% knock-down of MtDefMd1/MtDefMd2 expression did not significantly affect arbuscule size. Although overexpression of MtDefMd1 in arbuscule-containing cells led to an up-regulation of MtRam1, encoding a key transcriptional regulator of arbuscule formation, no morphological changes were evident. Co-localization of an MtDefMd1-mGFP6 fusion with additional, subcellular markers revealed that this defensin is associated with arbuscules in later stages of their life-cycle. MtDefMd1-mGFP6 was detected in cells with older arbuscules about to collapse, and ultimately in vacuolar compartments. Comparisons with mycorrhized roots expressing a tonoplast marker indicated that MtDefMd1 acts during late restructuring processes of arbuscule-containing cells, upon their transition into a post-symbiotic state.

  12. Antibacterial activity of defensin PaDef from avocado fruit (Persea americana var. drymifolia) expressed in endothelial cells against Escherichia coli and Staphylococcus aureus.

    Guzmán-Rodríguez, Jaquelina Julia; López-Gómez, Rodolfo; Suárez-Rodríguez, Luis M; Salgado-Garciglia, Rafael; Rodríguez-Zapata, Luis C; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

    2013-01-01

    Antimicrobial therapy is a useful tool to control infectious diseases in general and rising antibiotic resistant microorganisms in particular. Alternative strategies are desirable, and antimicrobial peptides (AMP) represent attractive control agents. Mexican avocado (Persea americana var. drymifolia) is used in traditional medicine; however, the AMP production has not been reported in this plant. We obtained a cDNA library from avocado fruit and clone PaDef was identified, which has a cDNA (249 bp) encoding a protein (78 aa) homologous with plant defensins (>80%). We expressed the defensin PaDef cDNA (pBME3) in the bovine endothelial cell line BVE-E6E7. Polyclonal and clonal populations were obtained and their activity was evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans. E. coli viability was inhibited with 100 μg/mL of total protein from clones (>55%). Also, S. aureus viability was inhibited from 50 μg/mL total protein (27-38%) but was more evident at 100 μg/mL (52-65%). This inhibition was higher than the effect showed by polyclonal population (~23%). Finally, we did not detect activity against C. albicans. These results are the first report that shows antimicrobial activity of a defensin produced by avocado and suggest that this AMP could be used in the control of pathogens.

  13. Antibacterial Activity of Defensin PaDef from Avocado Fruit (Persea americana var. drymifolia Expressed in Endothelial Cells against Escherichia coli and Staphylococcus aureus

    Jaquelina Julia Guzmán-Rodríguez

    2013-01-01

    Full Text Available Antimicrobial therapy is a useful tool to control infectious diseases in general and rising antibiotic resistant microorganisms in particular. Alternative strategies are desirable, and antimicrobial peptides (AMP represent attractive control agents. Mexican avocado (Persea americana var. drymifolia is used in traditional medicine; however, the AMP production has not been reported in this plant. We obtained a cDNA library from avocado fruit and clone PaDef was identified, which has a cDNA (249 bp encoding a protein (78 aa homologous with plant defensins (>80%. We expressed the defensin PaDef cDNA (pBME3 in the bovine endothelial cell line BVE-E6E7. Polyclonal and clonal populations were obtained and their activity was evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans. E. coli viability was inhibited with 100 μg/mL of total protein from clones (>55%. Also, S. aureus viability was inhibited from 50 μg/mL total protein (27–38% but was more evident at 100 μg/mL (52–65%. This inhibition was higher than the effect showed by polyclonal population (~23%. Finally, we did not detect activity against C. albicans. These results are the first report that shows antimicrobial activity of a defensin produced by avocado and suggest that this AMP could be used in the control of pathogens.

  14. Comparison of the nodule vs. root transcriptome of the actinorhizal plant Datisca glomerata: actinorhizal nodules contain a specific class of defensins.

    Irina V Demina

    Full Text Available Actinorhizal root nodule symbioses are very diverse, and the symbiosis of Datisca glomerata has previously been shown to have many unusual aspects. In order to gain molecular information on the infection mechanism, nodule development and nodule metabolism, we compared the transcriptomes of D. glomerata roots and nodules. Root and nodule libraries representing the 3'-ends of cDNAs were subjected to high-throughput parallel 454 sequencing. To identify the corresponding genes and to improve the assembly, Illumina sequencing of the nodule transcriptome was performed as well. The evaluation revealed 406 differentially regulated genes, 295 of which (72.7% could be assigned a function based on homology. Analysis of the nodule transcriptome showed that genes encoding components of the common symbiosis signaling pathway were present in nodules of D. glomerata, which in combination with the previously established function of SymRK in D. glomerata nodulation suggests that this pathway is also active in actinorhizal Cucurbitales. Furthermore, comparison of the D. glomerata nodule transcriptome with nodule transcriptomes from actinorhizal Fagales revealed a new subgroup of nodule-specific defensins that might play a role specific to actinorhizal symbioses. The D. glomerata members of this defensin subgroup contain an acidic C-terminal domain that was never found in plant defensins before.

  15. Diagnosis of acute and chronic enteric fever using metabolomics

    Näsström, Elin

    2017-01-01

    Enteric (or typhoid) fever is a systemic infection mainly caused by Salmonella Typhi and Salmonella Paratyphi A. The disease is common in areas with poor water quality and insufficient sanitation. Humans are the only reservoir for transmission of the disease. The presence of asymptomatic chronic carriers is a complicating factor for the transmission. There are major limitations regarding the current diagnostic methods both for acute infection and chronic carriage. Metabolomics is a methodolog...

  16. Intestinal endocrine cells in radiation enteritis

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  17. Enteral nutrition in inflammatory bowel disease.

    Gassull, M A; Abad, A; Cabré, E; González-Huix, F; Giné, J J; Dolz, C

    1986-01-01

    To assess the effect of the addition of enteral tube feeding with polymeric diets to the standard treatment of acute attacks of inflammatory bowel disease a total of 43 patients admitted to hospital (23 with Crohn's disease and 20 with ulcerative colitis) were studied retrospectively. Total enteral nutrition was given to 26 as the sole nutritional supply and to 17 in conjunction with a normal ward diet, when appropriate, according to the severity of attack (control group). Nutritional state was assessed and classified in all patients at admission and at the end of the study, by measuring the triceps skinfold thickness, mid arm muscle circumference, and serum albumin concentration as representative of body fat, muscle protein, and visceral protein, respectively. At admission the three nutritional variables were not statistically different between the groups. There was a significantly positive effect on mid arm muscle circumference in patients on total enteral nutrition compared with the control group, but there was no effect on either triceps skinfold thickness or serum albumin concentration. The percentage of subjects requiring intravenous albumin infusion, however, was significantly less in the group fed enterally than in the control group. In addition, fewer patients in the group fed enterally required surgical treatment compared with the control group, despite the fact that one of the criteria for starting enteral nutritional support was the expectancy that surgery would be needed. Total enteral nutrition was well tolerated and no major side effects arose during its use in patients with acute exacerbations of inflammatory bowel disease. PMID:3098646

  18. Bacteriophages as indicators of faecal pollution and enteric virus removal.

    McMinn, B R; Ashbolt, N J; Korajkic, A

    2017-07-01

    Bacteriophages are an attractive alternative to faecal indicator bacteria (FIB), particularly as surrogates of enteric virus fate and transport, due to their closer morphological and biological properties. Based on a review of published data, we summarize densities of coliphages (F+ and somatic), Bacteroides spp. and enterococci bacteriophages (phages) in individual human waste, raw wastewater, ambient fresh and marine waters and removal through wastewater treatment processes utilizing traditional treatments. We also provide comparisons with FIB and enteric viruses whenever possible. Lastly, we examine fate and transport characteristics in the aquatic environment and provide an overview of the environmental factors affecting their survival. In summary, concentrations of bacteriophages in various sources were consistently lower than FIB, but more reflective of infectious enteric virus levels. Overall, our investigation indicates that bacteriophages may be adequate viral surrogates, especially in built systems, such as wastewater treatment plants. Bacteriophage are alternative fecal indicators that may be better surrogates for viral pathogens than fecal indicator bacteria (FIB). This report offers a summary of the existing literature concerning the utility of bacteriophage as indicators of viral presence (fecal sources and surface waters) and persistence (in built infrastructure and aquatic environments). Our findings indicate that bacteriophage levels in all matrices examined are consistently lower than FIB, but similar to viral pathogens. Furthermore, in built infrastructure (e.g. wastewater treatment systems) bacteriophage closely mimic viral pathogen persistence suggesting they may be adequate sentinels of enteric virus removal. © 2017 The Society for Applied Microbiology.

  19. Vitamin D Signaling Through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models

    Danmei Su

    2016-11-01

    Full Text Available Metabolic syndrome (MetS, characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD,is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR is highly expressed in the ileum of the small intestine,which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD is necessary but not sufficient, while additional vitamin D deficiency (VDD as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD, the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5, MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD, Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with

  20. American Society for Parenteral & Enteral Nutrition

    ... Center Advertising and Sponsorship Learn More ASPEN Enteral Nutrition by the Numbers: EN Data Across the Healthcare Continuum Learn More The ASPEN Adult Nutrition Support Core Curriculum, 3rd Edition Has Arrived! The ...

  1. effects of enteral glutamine supplementation on reduction

    Objective: To determine the effect of enteral glutamine in reducing the incidence of ... in use. These modalities include among others; topical antibacterial agents, early excision of eschar, and ... in the burns unit and plastic surgery ward 4D of.

  2. [Indications and practice of enteral nutrition].

    Hallay, Judit; Nagy, Dániel; Fülesdi, Béla

    2014-12-21

    Malnutrition in hospitalised patients has a significant and disadvantageous impact on treatment outcome. If possible, enteral nutrition with an energy/protein-balanced nutrient should be preferred depending on the patient's condition, type of illness and risk factors. The aim of the nutrition therapy is to increase the efficacy of treatment and shorten the length of hospital stay in order to ensure rapid rehabilitation. In the present review the authors summarize the most important clinical and practical aspects of enteral nutrition therapy.

  3. Do enteric neurons make hypocretin? ☆

    Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

    2007-01-01

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, s...

  4. Expression of beta-defensins pBD-1 and pBD-2 along the small intestinal tract of the pig: lack of upregulation in vivo upon Salmonella typhimurium infection.

    Veldhuizen, Edwin J A; van Dijk, Albert; Tersteeg, Monique H G; Kalkhove, Stefanie I C; van der Meulen, Jan; Niewold, Theo A; Haagsman, Henk P

    2007-01-01

    Defensins are antimicrobial peptides that play an important role in the innate immune response in the intestine. Up to date, only one beta-defensin (pBD-1), has been described in pig, which was found to be expressed at low levels in the intestine. We set-up a quantitative PCR method to detect the gene expression of pBD-1 and a newly discovered porcine beta-defensin, pBD-2. Expression of pBD-1 mRNA increased from the proximal to the distal part of the intestine whereas pBD-2 expression decreased. The main gene expression sites for pBD-2 were kidney and liver, whereas pBD-1 was mainly expressed in tongue. The porcine small intestinal segment perfusion (SISP) technique was used to investigate effects of Salmonella typhimurium DT104 on intestinal morphology and pBD-1 and pBD-2 mRNA levels in vivo. The early responses were studied 2, 4 and 8 h post-infection in four separate jejunal and ileal segments. Immunohistochemistry showed invasion of the mucosa by Salmonella and changes in intestinal morphology. However, no concomitant changes in expression of either pBD-1 or pBD-2 were observed. We conclude that at least two defensins are differentially expressed in the intestine of pigs, and that expression of both defensins is not altered by S. typhimurium under these conditions.

  5. Construction of rat beta defensin-2 eukaryotic expression vector and expression in the transfected rat corneal epithelial cell

    Jing Dan

    2017-03-01

    Full Text Available AIM: To construct a recombinant eukaryotic expression vector of rat beta defensin-2(rBD-2, transfect it into the rat corneal epithelial cells with lipofection, determine the expression of target gene in the transfected cells, and discuss the potentiality of recombinant plasmid expressed in corneal epithelial cells, hoping to provide an experimental foundation for further study on the antimicrobial activity of rBD-2 in vitro and in vivo and to assess the probability of defensins as a new application for infectious corneal diseases in the future. METHODS: The synthetic rBD-2 DNA fragment was inserted between the XhoI and BamHI restriction enzyme cutting sites of eukaryotic expression vector pIRES2-ZsGreen1 to construct the recombinant plasmid pIRES2-ZsGreen1-rBD-2, then transformed it into E.coli DH5α, positive clones were screened by kanamycin and identified with restriction endonucleases and sequencing analysis. Transfection into the rat corneal epithelial cells was performed by lipofection. Then the experiment was divided into three groups: rat corneal epithelial cell was transfected with the recombinant plasmid pIRES2- ZsGreen1-rBD-2, rat corneal epithelial cell was transfected with the empty plasmid pIRES2-ZsGreen1 and the non-transfected group. The inverted fluorescence microscope was used to observe the transfection process. At last, the level of rBD-2 mRNA expressed in the transfected cells and the control groups are compared by the real-time fluoresence relative quantitative PCR. RESULTS: The recombinant eukaryotic expression vector of pIRES2-ZsGreen1-rBD-2 was successfully constructed. The level of rBD-2 mRNA in transfected cells was significantly higher than that in control groups through the real-time fluorescence relative quantitative PCR. CONCLUSION: The recombinant eukaryotic expression vector pIRES2-ZsGreen1-rBD-2 could be transfected into rat corneal epithelial cells, and exogenous rBD-2 gene could be transcripted into mRNA in

  6. Laboratory Screening for Children Entering Foster Care.

    Greiner, Mary V; Beal, Sarah J; Nause, Katie; Staat, Mary Allen; Dexheimer, Judith W; Scribano, Philip V

    2017-12-01

    To determine the prevalence of medical illness detected by laboratory screening in children entering foster care in a single, urban county. All children entering foster care in a single county in Ohio were seen at a consultation foster care clinic and had laboratory screening, including testing for infectious diseases such as HIV, hepatitis B, hepatitis C, syphilis, and tuberculosis as well as for hemoglobin and lead levels. Over a 3-year period (2012-2015), laboratory screening was performed on 1977 subjects entering foster care in a consultative foster care clinic. The prevalence of hepatitis B, hepatitis C, syphilis, and tuberculosis were all found to be <1%. There were no cases of HIV. Seven percent of teenagers entering foster care tested positive for Chlamydia . A secondary finding was that 54% of subjects were hepatitis B surface antibody-negative, indicating an absence of detected immunity to the hepatitis B virus. Routine laboratory screening for children entering foster care resulted in a low yield. Targeted, rather than routine, laboratory screening may be a more clinically meaningful approach for children entering foster care. Copyright © 2017 by the American Academy of Pediatrics.

  7. Enteric Duplication Cysts in Children: A Clinicopathological Dilemma.

    Sharma, Sonam; Yadav, Amit K; Mandal, Ashish K; Zaheer, Sufian; Yadav, Devendra K; Samie, Amat

    2015-08-01

    Enteric duplication cysts are rare and uncommon congenital malformations formed during the embryonic period of the development of human digestive system and are mainly encountered during infancy or early childhood, but seldom in adults. The clinical presentation is extremely variable depending upon its size, location and type. We present six cases of enteric duplication cysts with diverse clinico-pathological features. This study was carried out in the Department of Pathology and Department of Paediatric Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India for a period of 2 years (January 2013 - December 2014). We retrospectively analyzed six patients of enteric duplication cysts based on data obtained, which consisted of patient's age, sex, clinical presentation, radiological features, operative findings and histopathology report. The data collected was analyzed by descriptive statistics. Six children between age range of 3 days to 10 years had enteric duplication cysts. Two had ileal and one each were of pyloroduodenal, colonic and rectal duplication cyst. In one patient a presumptive diagnosis of enteric duplication cyst was made. Radiology played an important contributory role in diagnosis of these cysts in all the patients but histopathology proved to be gold standard for its confirmation. All these patients were managed by surgical excision. The postoperative and follow up period in all the cases was uneventful. It is important to be aware and make a definitive diagnosis of this rare congenital anomaly as they can present in various clinical forms and can cause significant morbidity and even mortality if left untreated by causing life threatening complications.

  8. Enteric Protozoa in the Developed World: a Public Health Perspective

    Fletcher, Stephanie M.; Stark, Damien; Harkness, John

    2012-01-01

    Summary: Several enteric protozoa cause severe morbidity and mortality in both humans and animals worldwide. In developed settings, enteric protozoa are often ignored as a cause of diarrheal illness due to better hygiene conditions, and as such, very little effort is used toward laboratory diagnosis. Although these protozoa contribute to the high burden of infectious diseases, estimates of their true prevalence are sometimes affected by the lack of sensitive diagnostic techniques to detect them in clinical and environmental specimens. Despite recent advances in the epidemiology, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist, requiring further research. There is evidence that climate-related changes will contribute to their burden due to displacement of ecosystems and human and animal populations, increases in atmospheric temperature, flooding and other environmental conditions suitable for transmission, and the need for the reuse of alternative water sources to meet growing population needs. This review discusses the common enteric protozoa from a public health perspective, highlighting their epidemiology, modes of transmission, prevention, and control. It also discusses the potential impact of climate changes on their epidemiology and the issues surrounding waterborne transmission and suggests a multidisciplinary approach to their prevention and control. PMID:22763633

  9. Scheme for Entering Binary Data Into a Quantum Computer

    Williams, Colin

    2005-01-01

    A quantum algorithm provides for the encoding of an exponentially large number of classical data bits by use of a smaller (polynomially large) number of quantum bits (qubits). The development of this algorithm was prompted by the need, heretofore not satisfied, for a means of entering real-world binary data into a quantum computer. The data format provided by this algorithm is suitable for subsequent ultrafast quantum processing of the entered data. Potential applications lie in disciplines (e.g., genomics) in which one needs to search for matches between parts of very long sequences of data. For example, the algorithm could be used to encode the N-bit-long human genome in only log2N qubits. The resulting log2N-qubit state could then be used for subsequent quantum data processing - for example, to perform rapid comparisons of sequences.

  10. Regulatory patterns of a large family of defensin-like genes expressed in nodules of Medicago truncatula.

    Sumitha Nallu

    Full Text Available Root nodules are the symbiotic organ of legumes that house nitrogen-fixing bacteria. Many genes are specifically induced in nodules during the interactions between the host plant and symbiotic rhizobia. Information regarding the regulation of expression for most of these genes is lacking. One of the largest gene families expressed in the nodules of the model legume Medicago truncatula is the nodule cysteine-rich (NCR group of defensin-like (DEFL genes. We used a custom Affymetrix microarray to catalog the expression changes of 566 NCRs at different stages of nodule development. Additionally, bacterial mutants were used to understand the importance of the rhizobial partners in induction of NCRs. Expression of early NCRs was detected during the initial infection of rhizobia in nodules and expression continued as nodules became mature. Late NCRs were induced concomitantly with bacteroid development in the nodules. The induction of early and late NCRs was correlated with the number and morphology of rhizobia in the nodule. Conserved 41 to 50 bp motifs identified in the upstream 1,000 bp promoter regions of NCRs were required for promoter activity. These cis-element motifs were found to be unique to the NCR family among all annotated genes in the M. truncatula genome, although they contain sub-regions with clear similarity to known regulatory motifs involved in nodule-specific expression and temporal gene regulation.

  11. The spectrum of radiation enteritis: surgical considerations

    Haddad, G.K.; Grodsinsky, C.; Allen, H.

    1983-01-01

    Radiation therapy, often used to treat gynecologic and urologic pelvic malignancies, has varying, adverse effects on the bowel. Radiation enteritis may occur from one month to 20 years after irradiation, and disabling symptoms may require surgery in 10 to 20 per cent of patients. From our experience with 20 patients who required surgery for radiation enteritis and who were followed for up to 20 years, we were able to identify three clinical groups. Patients in the first group need only medical treatment for their symptoms, and observation, whereas patients in the second group may present with acute, debilitating, life-threatening symptoms that may require emergency surgery. Patients in the third group have a long-standing history of intermittent bowel obstruction and/or enteric fistulas that are best treated with adequate nutritional support followed by timely surgical intervention

  12. The radiological features of chronic radiation enteritis

    Mendelson, R.M.; Nolan, D.J.

    1985-01-01

    The radiological findings, using a single-contrast barium infusion technique, are described in a series of 13 patients with chronic radiation enteritis. The signs include evidence of submucosal thickening, single or multiple stenoses, adhesions and sinus or fistula formation. A combination of these signs characterises the condition. This technique is particularly suited to the investigation of radiation enteritis because of its ability to distend maximally the small intestine. A cause, stenosis and/or adhesions, was demonstrated in the eight of the 13 patients presenting with intermittent small-intestinal obstruction. Three patients had diarrhoea as their predominant complaint and a fistula was demonstrated in two. (author)

  13. Effect Of Oligomeric Enteral Nutrition On Symptoms Of Acute Radiation Enteritis

    Dubinsky, P.

    2008-01-01

    Radiotherapy of abdominal and pelvic tumours is frequently associated with acute radiation enteritis. Predominant symptoms include diarrhea, watery stools, abdominal pain, nausea and vomiting. There are very few effective interventions available for this condition. Enteral oligomeric nutrition has been used in bowel diseases with functional failure similar to radiation enteritis. The aim of presented work was to observe occurrence of symptoms of radiation enteritis in patients undergoing abdominal or pelvic radiotherapy. Apart from diet and pharmacological therapy, oral oligomeric enteral nutrition (Peptisorb Powder Nutricia) at the dose of 1000 - 2000 ml per day was administered for minimum of 4 days. Planned period of administration was 14 days and longer. Symptoms of radiation enteritis were evaluated at the beginning and in the end of administration. Prevalence of all evaluated symptoms of radiation enteritis was decreased and difference was statistically significant for diarrhea, watery stools, abdominal pain, nausea and vomiting. The use of evaluated oligomeric nutritional support might, in conjunction with pharmacotherapy and diet, alleviate symptoms of acute radiation enteritis and maintain nutritional status of patients. (author)

  14. The β-Defensin Gallinacin-6 Is Expressed in the Chicken Digestive Tract and Has Antimicrobial Activity against Food-Borne Pathogens▿

    van Dijk, Albert; Veldhuizen, Edwin J. A.; Kalkhove, Stefanie I. C.; Tjeerdsma-van Bokhoven, Johanna L. M.; Romijn, Roland A.; Haagsman, Henk P.

    2007-01-01

    Food-borne pathogens are responsible for most cases of food poisoning in developed countries and are often associated with poultry products, including chicken. Little is known about the role of β-defensins in the chicken digestive tract and their efficacy. In this study, the expression of chicken β-defensin gallinacin-6 (Gal-6) and its antimicrobial activity against food-borne pathogens were investigated. Reverse transcription-PCR analysis showed high expression of Gal-6 mRNA in the esophagus and crop, moderate expression in the glandular stomach, and low expression throughout the intestinal tract. Putative transcription factor binding sites for nuclear factor kappa beta, activator protein 1, and nuclear factor interleukin-6 were found in the Gal-6 gene upstream region, which suggests a possible inducible nature of the Gal-6 gene. In colony-counting assays, strong bactericidal and fungicidal activity was observed, including bactericidal activity against food-borne pathogens Campylobacter jejuni, Salmonella enterica serovar Typhimurium, Clostridium perfringens, and Escherichia coli. Treatment with 16 μg/ml synthetic Gal-6 resulted in a 3 log unit reduction in Clostridium perfringens survival within 60 min, indicating fast killing kinetics. Transmission electron microscopy examination of synthetic-Gal-6-treated Clostridium perfringens cells showed dose-dependent changes in morphology after 30 min, including intracellular granulation, cytoplasm retraction, irregular septum formation in dividing cells, and cell lysis. The high expression in the proximal digestive tract and broad antimicrobial activity suggest that chicken β-defensin gallinacin-6 plays an important role in chicken innate host defense. PMID:17194828

  15. Enteric coating of granules containing the probiotic Lactobacillus acidophilus

    Pyar Hassan

    2014-06-01

    Full Text Available In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

  16. Enteric and indicator virus removal by surface flow wetlands.

    Rachmadi, Andri T; Kitajima, Masaaki; Pepper, Ian L; Gerba, Charles P

    2016-01-15

    We investigated the occurrence and attenuation of several human enteric viruses (i.e., norovirus, adenovirus, Aichi virus 1, polyomaviruses, and enterovirus) as well as a plant virus, pepper mild mottle virus (PMMoV), at two surface flow wetlands in Arizona. The retention time in one of the wetlands was seven days, whereas in the other wetland it could not be defined. Water samples were collected at the inlet and outlet from the wetlands over nine months, and concentration of viral genomes was determined by quantitative polymerase chain reaction (qPCR). Of the human enteric viruses tested, adenovirus and Aichi virus 1 were found in the greatest prevalence in treated wastewater (i.e., inlet of the wetlands). Reduction efficiencies of enteric viruses by the wetlands ranged from 1 to 3 log10. Polyomaviruses were generally removed to below detection limit, indicating at least 2 to 4 log10 removal. PMMoV was detected in a greater concentration in the inlet of both wetlands for all the viruses tested (10(4) to 10(7) genome copies/L), but exhibited little or no removal (1 log10 or less). To determine the factors associated with virus genome attenuation (as determined by qPCR), the persistence of PMMoV and poliovirus type 1 (an enterovirus) was studied in autoclaved and natural wetland water, and deionized water incubated under three different temperatures for 21 days. A combination of elevated water temperature and biological activities reduced poliovirus by 1 to 4 log10, while PMMoV was not significantly reduced during this time period. Overall, PMMoV showed much greater persistence than human viruses in the wetland treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

    Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

    2017-12-01

    Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the

  18. Isolated Enteric Cyst in the Neck

    Amit Mahore

    2014-01-01

    Full Text Available We report an extremely rare case of isolated enteric cyst in the neck region which was diagnosed on the histopathological examination. It was suspected to be duplication cyst on radiology. We have also evaluated the differential diagnosis and management issues.

  19. Hypophosphatemia associated with enteral alimentation in cats.

    Justin, R B; Hohenhaus, A E

    1995-01-01

    Hypophosphatemia is uncommon in cats, but it has been reported in association with diabetes mellitus and hepatic lipidosis, where it can cause hemolysis, rhabdomyopathy, depression, seizures, and coma. The purpose of this article is to describe 9 cats that developed low serum phosphorus concentrations (alimentation. Serum biochemical analyses from more than 6,000 cats were reviewed. The medical records of all cats with hypophosphatemia were examined for history of enteral alimentation; diabetic cats were excluded from the study. Nine cats, ranging in age from 3 to 17 years, were identified. All cats had normal serum phosphorus concentrations before tube feeding began. Onset of hypophosphatemia occurred 12 to 72 hours after initiation of enteral alimentation, and the nadir for phosphorus concentrations ranged from 0.4 to 2.4 mg/dL. Hemolysis occurred in 6 of the 9 cats. Hypophosphatemia secondary to enteral alimentation is an uncommon clinical finding in cats. Cats with high alanine aminotransferase activity, hyperbilirubinemia, and weight loss should be closely monitored for hypophosphatemia during the first 72 hours of enteral alimentation.

  20. [Enteral alimentation at home: why PEG now?].

    Suzuki, Y; Hanyu, N; Kashiwagi, H; Kubo, T; Aoki, T

    1996-12-01

    The history of percutaneous endoscopic gastrostomy (PEG) is relatively short. In 1980, a report entitled "Gastrostomy without laparotomy: A percutaneous endoscopic technique" by Ponsky and Gaudere was first published in the Journal of Pediatric Surgery. Thereafter, PEG soon saw widespread use in Western countries because of its clinical efficacy and economy. It has been performed in about 170,000 cases annually in the US. In contrast, its spread in Japan has been extremely slow: only about 10,000 cases have undergone this procedure annually, and this number accounted for less than 5% of patients receiving enteral alimentation. The reason why PEG has not spread may be the medical insurance system in Japan and the local distaste for operation scarring. However, in consideration of the unprecedented ageing of society that is surely coming in the near future, the role of PEG in Japan must be reexamined. In this report, we presented the methodology of enteral alimentation at home by means of PEG, giving special consideration to: (1) "What points are improved by using enteral alimentation at home by means of PEG in various diseases; (2) dysphagia due to cerebral angiopathy; (3) terminal cancer; (4) otolaryngological diseases; and (5) Crohn disease. We also discussed "Why PEG is important now?" in performing enteral alimentation at home.

  1. Aspects of enteral nutrition in cancer chemotherapy

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients

  2. Entering a Crack: An Encounter with Gossip

    Henderson, Linda

    2014-01-01

    In this paper, I enter a crack to think otherwise about the concept "gossip". Drawing on previous scholarship engaging with Deleuzian concepts to inform research methodologies, this paper builds on this body of work. Following Deleuze and Guattari, the paper undertakes a mapping of gossip, subsequent to an encounter with a crack.…

  3. Kokainudløst iskaemisk enteritis

    Hobolth, Lise; Bendtsen, Flemming

    2009-01-01

    and a pill cam capsule endoscopy were normal. In all cases the condition normalized spontaneously. A thorough interview revealed a recreational use of cocaine, and diary recordings confirmed the association between her abdominal pain and cocaine use. Ischaemic enteritis has previously been described...

  4. Astronaut John Glenn Enters Friendship 7

    1962-01-01

    Astronaut John Glenn enters the Mercury spacecraft, Friendship 7, prior to the launch of MA-6 on February 20, 1961 and became the first American who orbited the Earth. The MA-6 mission was the first manned orbital flight boosted by the Mercury-Atlas vehicle, a modified Atlas ICBM (Intercontinental Ballistic Missile), lasted for five hours, and orbited the Earth three times.

  5. Intestinal endocrine cells in radiation enteritis

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  6. The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection: A Systematic Review and Meta-Analysis.

    Wyatt, M C; Beswick, A D; Kunutsor, S K; Wilson, M J; Whitehouse, M R; Blom, A W

    2016-06-15

    Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria. We performed a systematic review to identify diagnostic technique studies evaluating the accuracy of alpha-defensin or leukocyte esterase in the diagnosis of PJI. MEDLINE and Embase on Ovid, ACM, ADS, arXiv, CERN DS (Conseil Européen pour la Recherche Nucléaire Document Server), CrossRef DOI (Digital Object Identifier), DBLP (Digital Bibliography & Library Project), Espacenet, Google Scholar, Gutenberg, HighWire, IEEE Xplore (Institute of Electrical and Electronics Engineers digital library), INSPIRE, JSTOR (Journal Storage), OAlster (Open Archives Initiative Protocol for Metadata Harvesting), Open Content, Pubget, PubMed, and Web of Science were searched for appropriate studies indexed from inception until May 30, 2015, along with unpublished or gray literature. The classification of studies and data extraction were performed independently by 2 reviewers. Data extraction permitted meta-analysis of sensitivity and specificity with construction of receiver operating characteristic curves for each test. We included 11 eligible studies. The pooled diagnostic sensitivity and specificity of alpha-defensin (6 studies) for PJI were 1.00 (95% confidence interval [CI], 0.82 to 1.00) and 0.96 (95% CI, 0.89 to 0.99), respectively. The area under the curve (AUC) for alpha-defensin and PJI was 0.99 (95% CI, 0.98 to 1.00). The pooled diagnostic sensitivity and specificity of leukocyte esterase (5 studies) for PJI were 0.81 (95% CI, 0.49 to 0.95) and 0.97 (95% CI, 0.82 to 0.99), respectively. The AUC for leukocyte esterase and PJI was 0.97 (95% CI, 0.95 to 0

  7. The Role of α-Defensins 1–3 in Antimicrobial Protection Forming in Children with Recurrent Bronchitis Caused by Bacteria of the Genus Haemophilus

    G.O. Lezhenko

    2013-03-01

    Full Text Available The level of α-defensins 1–3 (HNP 1–3 has been analyzed in the blood plasma of children with recurrent bronchitis caused by bacteria of the genus Haemophilus. It is shown that the level of HNP 1–3 in the blood plasma depends on the form of Haemophilus. Trigger of HNP 1–3 outflow for neutrophils was the presence of bacterial capsule while presence of L-forms of Haemophilus influenzae wasn’t associated with increase in synthesis of antimicrobial peptides that could be one of the factors of forming of Haemophilus antibiotic resistance.

  8. Syndromic diarrhea/Tricho-hepato-enteric syndrome

    Fabre Alexandre

    2013-01-01

    Full Text Available Abstract Syndromic diarrhea/Tricho-hepato-enteric syndrome (SD/THE is a rare and severe bowel disorder caused by mutation in SKIV2L or in TTC37, 2 genes encoding subunits of the putative human SKI complex. The estimated prevalence is 1/1,000,000 births and the transmission is autosomal recessive. The classical form is characterized by 5 clinical signs: intractable diarrhea of infancy beginning in the first month of life, usually leading to failure to thrive and requiring parenteral nutrition; facial dysmorphism characterised by prominent forehead and cheeks, broad nasal root and hypertelorism; hair abnormalities described as woolly and easily removable; immune disorders resulting from defective antibody production; intrauterine growth restriction. The aetiology is a defect in TTC37, a TPR containing protein, or in the RNA helicase SKIV2L, both constituting the putative human ski complex. The ski complex is a heterotetrameric cofactor of the cytoplasmic RNA exosome which ensures aberrants mRNAs decay. The diagnosis SD/THE is initially based on clinical findings and confirmed by direct sequencing of TTC37 and SKIV2L. Differential diagnosis with the other causes of intractable diarrhea is easily performed by pathologic investigations. During their clinical course, most of the children require parenteral nutrition and often immunoglobulin supplementation. With time, some of them can be weaned off parenteral nutrition and immunoglobulin supplementation. The prognosis depends on the management and is largely related to the occurrence of parenteral nutrition complications or infections. Even with optimal management, most of the children seem to experience failure to thrive and final short stature. Mild mental retardation is observed in half of the cases. Abstract in French Les diarrhées syndromiques ou syndrome tricho-hepato-enterique (SD/THE sont un syndrome rare et sévère dont l’incidence est estimée à 1 cas pour 1 million de naissances et la

  9. Genome-Wide Sensitivity Analysis of the Microsymbiont Sinorhizobium meliloti to Symbiotically Important, Defensin-Like Host Peptides

    Markus F. F. Arnold

    2017-08-01

    Full Text Available The model legume species Medicago truncatula expresses more than 700 nodule-specific cysteine-rich (NCR signaling peptides that mediate the differentiation of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides are essential for a successful symbiosis in legume plants of the inverted-repeat-lacking clade (IRLC and show similarity to mammalian defensins. In addition to signaling functions, many NCR peptides exhibit antimicrobial activity in vitro and in vivo. Bacterial resistance to these antimicrobial activities is likely to be important for symbiosis. However, the mechanisms used by S. meliloti to resist antimicrobial activity of plant peptides are poorly understood. To address this, we applied a global genetic approach using transposon mutagenesis followed by high-throughput sequencing (Tn-seq to identify S. meliloti genes and pathways that increase or decrease bacterial competitiveness during exposure to the well-studied cationic NCR247 peptide and also to the unrelated model antimicrobial peptide polymyxin B. We identified 78 genes and several diverse pathways whose interruption alters S. meliloti resistance to NCR247. These genes encode the following: (i cell envelope polysaccharide biosynthesis and modification proteins, (ii inner and outer membrane proteins, (iii peptidoglycan (PG effector proteins, and (iv non-membrane-associated factors such as transcriptional regulators and ribosome-associated factors. We describe a previously uncharacterized yet highly conserved peptidase, which protects S. meliloti from NCR247 and increases competitiveness during symbiosis. Additionally, we highlight a considerable number of uncharacterized genes that provide the basis for future studies to investigate the molecular basis of symbiotic development as well as chronic pathogenic interactions.

  10. Diagnosis of prosthetic joint infection with alpha-defensin using a lateral flow device: a multicentre study.

    Berger, P; Van Cauter, M; Driesen, R; Neyt, J; Cornu, O; Bellemans, J

    2017-09-01

    The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176-82. ©2017 The British Editorial Society of Bone & Joint Surgery.

  11. Enteric methane emissions from German pigs

    Dämmgen, Ulrich; Schulz, Joachim; Klausing, Heinrich Kleine

    2012-01-01

    Methane emissions from enteric fermentation of pigs are object of emission reporting. Hitherto they were treated as part of the energy balance of pigs, in accordance with IPCC guidance documents. They were calculated from the gross energy intake rate and a constant methane conversion ratio....... Meanwhile numerous experimental data on methane emissions from enteric fermentation is available in Germany and abroad; the results are compiled in this work. These results also allow for a description of transformation processes in the hind gut and a subsequent establishment of models that relate emissions...... to feed and performance data. The model by Kirchgeßner et al. (1995) is based on German experimental data and reflects typical national diet compositions. It is used to quantify typical emissions and methane conversion ratios. The results agree with other experimental findings at home and abroad...

  12. Clinical and nutritional implications of radiation enteritis

    Beer, W.H.; Fan, A.; Halsted, C.H.

    1985-01-01

    The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value

  13. Clinical and nutritional implications of radiation enteritis

    Beer, W.H.; Fan, A.; Halsted, C.H.

    1985-01-01

    The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value.

  14. Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas.

    Pausch, Thomas; Adolph, Sarah; Felix, Klaus; Bauer, Andrea S; Bergmann, Frank; Werner, Jens; Hartwig, Werner

    Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

  15. Effects of entering adulthood during a recession

    Dettling, Lisa

    2016-01-01

    Current cohorts of young adults entered adulthood during an international labor and housing market crisis of a severity not experienced since the Great Depression. Concerns have arisen over the impacts on young adults’ employment, income, wealth, and living arrangements, and about whether these young adults constitute a “scarred generation” that will suffer permanent contractions in financial well-being. If true, knowing the mechanisms through which young adults’ finances have been affected h...

  16. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghoottama; Smith, Thomas J.; Shah, Dilip

    2013-12-04

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or to RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.

  17. Enteral Nutrition in Dementia: A Systematic Review

    Joanne Brooke

    2015-04-01

    Full Text Available The aim of this systematic review is to evaluate the role of enteral nutrition in dementia. The prevalence of dementia is predicted to rise worldwide partly due to an aging population. People with dementia may experience both cognitive and physical complications that impact on their nutritional intake. Malnutrition and weight loss in dementia correlates with cognitive decline and the progress of the disease. An intervention for long term eating difficulties is the provision of enteral nutrition through a Percutaneous Endoscopic Gastrostomy tube to improve both nutritional parameters and quality of life. Enteral nutrition in dementia has traditionally been discouraged, although further understanding of physical, nutritional and quality of life outcomes are required. The following electronic databases were searched: EBSCO Host, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar for publications from 1st January 2008 and up to and including 1st January 2014. Inclusion criteria included the following outcomes: mortality, aspiration pneumonia, pressure sores, nutritional parameters and quality of life. Each study included separate analysis for patients with a diagnosis of dementia and/or neurological disease. Retrospective and prospective observational studies were included. No differences in mortality were found for patients with dementia, without dementia or other neurological disorders. Risk factors for poor survival included decreased or decreasing serum albumin levels, increasing age or over 80 years and male gender. Evidence regarding pneumonia was limited, although did not impact on mortality. No studies explored pressure sores or quality of life.

  18. Defense Human Resources Activity > PERSEREC

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  19. Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies

    Gabrio Bassotti; Vincenzo Villanacci; Simona Fisogni; Elisa Rossi; Paola Baronio; Carlo Clerici; Christoph A Maurer; Gieri Cathomas; Elisabetta Antonelli

    2007-01-01

    The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently,some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neurogliopathies.

  20. Transgastrostomy jejunal intubation for enteric alimentation.

    McLean, G K; Rombeau, J L; Caldwell, M D; Ring, E J; Freiman, D B

    1982-12-01

    Malnourished patients who cannot maintain an adequate oral intake but have normal intestinal absorption and motility are candidates for enteric alimentation. When impaired gastric peristalsis or an increased risk for aspiration makes gastrostomy feeding unsafe, direct jejunal infusion is the preferred route of alimentation. Angiographic techniques were used to convert previously placed, simple gastrostomies to combined gastrostomy-jejunostomies in 14 patients. In 17 additional patients, a combined gastrostomy-jejunal tube was placed under local anesthesia; angiographic techniques assisted in the placement of 11 of these tubes.

  1. The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion.

    Christoph M Ernst

    2009-11-01

    Full Text Available Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs by the multiple peptide resistance factor (MprF protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin. MprF is a large membrane protein that modifies the anionic phospholipid phosphatidylglycerol with l-lysine, thereby diminishing the bacterial affinity for CAMPs. Its widespread occurrence recommends MprF as a target for novel antimicrobials, although the mode of action of MprF has remained incompletely understood. We demonstrate that the hydrophilic C-terminal domain and six of the fourteen proposed trans-membrane segments of MprF are sufficient for full-level lysyl-phosphatidylglycerol (Lys-PG production and that several conserved amino acid positions in MprF are indispensable for Lys-PG production. Notably, Lys-PG production did not lead to efficient CAMP resistance and most of the Lys-PG remained in the inner leaflet of the cytoplasmic membrane when the large N-terminal hydrophobic domain of MprF was absent, indicating a crucial role of this protein part. The N-terminal domain alone did not confer CAMP resistance or repulsion of the cationic test protein cytochrome c. However, when the N-terminal domain was coexpressed with the Lys-PG synthase domain either in one protein or as two separate proteins, full-level CAMP resistance was achieved. Moreover, only coexpression of the two domains led to efficient Lys-PG translocation to the outer leaflet of the membrane and to full-level cytochrome c repulsion, indicating that the N-terminal domain facilitates the flipping of Lys-PG. Thus, MprF represents a new class of lipid-biosynthetic enzymes with two separable functional domains that synthesize Lys-PG and facilitate Lys-PG translocation. Our study unravels crucial details on the molecular basis of an important bacterial immune evasion mechanism and it may help

  2. Genomic diversification of giant enteric symbionts reflects host dietary lifestyles

    Ngugi, David; Miyake, Sou; Cahill, Matthew; Vinu, Manikandan; Hackmann, Timothy J.; Blom, Jochen; Tietbohl, Matthew; Berumen, Michael L.; Stingl, Ulrich

    2017-01-01

    of metabolic diversification of enteric microbiota involved in the degradation of algal biomass in these fishes. The enteric microbiota is also phylogenetically and functionally simple relative to the complex lignocellulose-degrading microbiota of terrestrial

  3. Gastric emptying of enteric-coated tablets

    Park, H.M.; Chernish, S.M.; Rosenek, B.D.; Brunelle, R.L.; Hargrove, B.; Wellman, H.N.

    1984-01-01

    To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effect in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets

  4. Russian Gas Market: Entering New Era

    Mitrova, Tatiana; Molnar, Gergely

    2015-04-01

    After a period of extensive growth in the 2000's, the Russian gas industry is now facing numerous challenges. Mounting competition by independent producers and the development of new production by Gazprom, combined with stagnating domestic demand and weakening export markets, have created a situation of overproduction, made worse by western sanctions and low oil and gas prices. Expansion to the East thanks to the recent China deal is not expected to provide much relief before 2024. The coming decade will be critical for the industry and its outcome will largely depend on the government's pricing and institutional policies but the role of the state should remain essential. This document presents the key findings of the New CEDIGAZ report 'Russian Gas Market: Entering New Era'. The report analyses the ongoing changes in the Russian industry and the challenges to be met

  5. Enteric methane emissions from German dairy cows

    Dammgen, U; Rosemann, C; Haenel, H D

    2012-01-01

    Up to now, the German agricultural emission inventory used a model for the assessment of methane emissions from enteric fermentation that combined an estimate of the energy and feed requirements as a function of performance parameters and diet composition, with the constant methane conversion rate......, as stated by IPCC. A methane emission model was selected here that is based on German feed data. It was combined with the hitherto applied model describing energy requirements. The emission rates thus calculated deviate from those previously obtained. In the new model, the methane conversion rate is back......-calculated from emission rates and gross energy intake rates. For German conditions of animal performance and diet composition, the national means of methane conversion rates range between 71 kJ MJ(-1) and 61 kJ MJ(-1) for low and high performances (4700 kg animal(-1) a(-1) in 1990 to 7200 kg animal(-1) a(-1...

  6. Radiation enteritis. Evaluation of surgical cases

    Sato, M.; Sano, M.; Minakuchi, N.; Narisawa, T.; Takahashi, T. (Akita Univ. (Japan))

    1981-09-01

    Radiation enteritis with severe complications including intestinal bleeding, fistula, and stenosis were treated surgically in 9 cases. These 9 cases included 7 cases of cancer of the uterine cervix and 2 single cases of seminoma and melanoma. The patients received /sup 60/Co or Linac x-ray external irradiation with or without intracavitary irradiation by a radium needle. Radiation injury began with melena, vaginorectal fistula, and intestinal obstruction 3 to 18 months after irradiation. One patient with melena underwent colostomy and survived 2 years. One of the three patients with vaginorectal fistula who had colostomy survived 1.5 years. In intestinal obstruction, one patients had bypass operation and three patients had resection of the intestine and the other had both. Leakage was noted in one patient, but the others had favorable prognosis.

  7. Optimal Time to Enter a Retirement Village

    Jinhui Zhang

    2017-03-01

    Full Text Available We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree’s utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to their full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

  8. APOLLO 10 ASTRONAUT ENTERS LUNAR MODULE SIMULATOR

    1969-01-01

    Apollo 10 lunar module pilot Eugene A. Cernan prepares to enter the lunar module simulator at the Flight Crew Training Building at the NASA Spaceport. Cernan, Apollo 10 commander Thomas P. Stafford and John W. Young, command module pilot, are to be launched May 18 on the Apollo 10 mission, a dress rehearsal for a lunar landing later this summer. Cernan and Stafford are to detach the lunar module and drop to within 10 miles of the moon's surface before rejoining Young in the command/service module. Looking on as Cernan puts on his soft helmet is Snoopy, the lovable cartoon mutt whose name will be the lunar module code name during the Apollo 10 flight. The command/service module is to bear the code name Charlie Brown.

  9. Reactive Arthritis Caused by Yersinia enterocolitica Enteritis.

    Honda, Kazuya; Iwanaga, Nozomi; Izumi, Yasumori; Tsuji, Yoshika; Kawahara, Chieko; Michitsuji, Toru; Higashi, Shuntaro; Kawakami, Atsushi; Migita, Kiyoshi

    2017-01-01

    We report a case of reactive arthritis (ReA) triggered by Yersinia enterocolitica enteritis. A 24-year-old Japanese man developed polyarthritis in the lower limbs. Two weeks prior to these symptoms, he noted diarrhea, right lower abdominal pain and a fever. Y. enterocolitica was not isolated from a stool culture; however, he was diagnosed with ReA based on the colonoscopic findings of a high anti-Y. enterocolitica antibody titer and HLA-B27 antigen positivity. Following treatment with methotrexate and steroids, his arthritis improved. This is the first reported Japanese case of ReA in the English literature after a gastrointestinal infection caused by Y. enterocolitica.

  10. Enteral and parenteral lipid requirements of preterm infants.

    Lapillonne, Alexandre

    2014-01-01

    Lipids provide infants with most of their energy needs. The major portion of the fat in human milk is found in the form of triglycerides, the phospholipids and cholesterol contributing for only a small proportion of the total fat. Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for normal development of the central nervous system and have potential for long-lasting effects that extend beyond the period of dietary insufficiency. Given the limited and highly variable formation of docosahexaenoic acid (DHA) from α-linolenic acid, and because DHA is critical for normal retinal and brain development in the human, DHA should be considered to be conditionally essential during early development. In early enteral studies, the amount of LC-PUFAs administered in formula was chosen to produce the same concentration of arachidonic acid and DHA as in term breast milk. Recent studies report outcome data in preterm infants fed formula with DHA content 2-3 times higher than the current concentration. Overall, these studies show that providing larger amounts of DHA supplements is associated with better neurological outcomes and may provide other health benefits. One study further suggests that the smallest babies are the most vulnerable to DHA deficiency and likely to reap the greatest benefit from high-dose DHA supplementation. Current nutritional management may not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods and in very preterm/very low birth weight infants until due date and higher amounts than those routinely used are likely to be necessary to compensate for intestinal malabsorption, DHA oxidation, and early deficit. Recommendations for the healthcare provider are made in order to prevent lipid and more specifically LC-PUFA deficit. Research should be continued to fill the gaps in knowledge and to further refine the adequate intake for each group of preterm infants. © 2014 S. Karger AG, Basel.

  11. Compounded Apixaban Suspensions for Enteral Feeding Tubes.

    Caraballo, Maria L; Donmez, Seda; Nathan, Kobi; Zhao, Fang

    2017-07-01

    Objective: There is limited information on compounded apixaban formulations for administration via enteral feeding tubes. This study was designed to identify a suitable apixaban suspension formulation that is easy to prepare in a pharmacy setting, is compatible with commonly used feeding tubes, and has a beyond-use date of 7 days. Methods: Apixaban suspensions were prepared from commercially available 5-mg Eliquis tablets. Several vehicles and compounding methods were screened for ease of preparation, dosage accuracy, and tube compatibility. Two tubing types, polyurethane and polyvinyl chloride, with varying lengths and diameters, were included in the study. They were mounted on a peg board during evaluation to mimic the patient body position. A 7-day stability study of the selected formulation was also conducted. Results: Vehicles containing 40% to 60% Ora-Plus in water all exhibited satisfactory flowability through the tubes. The mortar/pestle compounding method was found to produce more accurate and consistent apixaban suspensions than the pill crusher or crushing syringe method. The selected formulation, 0.25 mg/mL apixaban in 50:50 Ora-Plus:water, was compatible with both tubing types, retaining >98% drug in posttube samples. The stability study also confirmed that this formulation was stable physically and chemically over 7 days of storage at room temperature. Conclusions: A suitable apixaban suspension formulation was identified for administration via enteral feeding tubes. The formulation consisted of 0.25 mg/mL apixaban in 50:50 Ora-Plus:water. The stability study results supported a beyond-use date of 7 days at room temperature.

  12. Enteral Feeding in Abdominal Compartment Syndrome

    Ye. V Grigoryev

    2009-01-01

    Full Text Available Objective: to substantiate the choice of a gastrointestinal tract (GIT function support regimen as a mode for correction of the abdominal compartment syndrome (ACS. Subjects and methods. Forty-three patients with different causes of inadequate GIT function of various origin and ACS (disseminated peritonitis (45%, pancreatitis (24%, and severe concomitant injury (31% were examined. Group 1 (control received complete parenteral nutritional feeding (n=23; APACHE II scores, 21±4; calculated probability of fatal outcome, 33.5%. In Group II (study, complete parenteral feeding in the first 24 hours after stabilization was supplemented with GIT function support with Pepsisorb (Nutricia in doses of 500, 1000, and 1500 ml on days 1, 2, and 3, respectively (n=20; APACHE II scores, 20±6; calculated probability of fatal outcome, 37.1%. During early enteral nutritional support, the SOFA score was significantly less than that in Group 1 on days 2—3; the oxygenation index significantly increased on day 3; the value of intra-abdominal hypertension decreased to the control values. The positive effect of the GIT function support regimen on regression of the multiple organ dysfunction syndrome (MODS was confirmed by the lowered levels of biological markers (von Willebrand factor (WF and endothelin-1 as markers of endothelial damage of MODS. Correlation analysis showed a direct correlation between the markers of endothelial damage and the SOFA scores (r=0.34; p=0.05 for WF and r=0.49;p=0.03 for endothelin. Conclusion. The GIT function support regimen via early enteral alimentation with Peptisorb, which was initiated in the first 24 hours after admission, is able to level off the manifestations of the early stages of the abdominal compartment syndrome, with the acceptable values of oxygen balance and water-electrolyte and osmotic homeostasis being achieved. Key words: abdominal compartment syndrome, nutritional support, biological markers, oxygenation index

  13. Mining free-text medical records for companion animal enteric syndrome surveillance.

    Anholt, R M; Berezowski, J; Jamal, I; Ribble, C; Stephen, C

    2014-03-01

    Large amounts of animal health care data are present in veterinary electronic medical records (EMR) and they present an opportunity for companion animal disease surveillance. Veterinary patient records are largely in free-text without clinical coding or fixed vocabulary. Text-mining, a computer and information technology application, is needed to identify cases of interest and to add structure to the otherwise unstructured data. In this study EMR's were extracted from veterinary management programs of 12 participating veterinary practices and stored in a data warehouse. Using commercially available text-mining software (WordStat™), we developed a categorization dictionary that could be used to automatically classify and extract enteric syndrome cases from the warehoused electronic medical records. The diagnostic accuracy of the text-miner for retrieving cases of enteric syndrome was measured against human reviewers who independently categorized a random sample of 2500 cases as enteric syndrome positive or negative. Compared to the reviewers, the text-miner retrieved cases with enteric signs with a sensitivity of 87.6% (95%CI, 80.4-92.9%) and a specificity of 99.3% (95%CI, 98.9-99.6%). Automatic and accurate detection of enteric syndrome cases provides an opportunity for community surveillance of enteric pathogens in companion animals. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Intestine, immunity, and parenteral nutrition in an era of preferred enteral feeding.

    Barrett, Meredith; Demehri, Farokh R; Teitelbaum, Daniel H

    2015-09-01

    To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration. There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition's deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation. Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer.

  15. Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

    Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S.

    2016-01-01

    dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization...... the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular...... of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes....

  16. Early enteral nutrition compared to outcome in critically ill trauma ...

    Objectives: The benefit of an early enteral nutrition start in critical ill patients is widely accepted. However, limited published data focus on trauma patients. This study aimed to investigate the effect of early enteral nutrition initiation on length of stay and mortality in an intensive care unit (ICU), as well as explore if enteral ...

  17. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mink Enteritis Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.204 Mink Enteritis Vaccine, Killed Virus. Mink Enteritis Vaccine...

  18. 30 CFR 77.1502 - Auger holes; restriction against entering.

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auger holes; restriction against entering. 77... UNDERGROUND COAL MINES Auger Mining § 77.1502 Auger holes; restriction against entering. No person shall be permitted to enter an auger hole except with the approval of the MSHA Coal Mine Safety and Health District...

  19. Expression of avian β-defensins and Toll-like receptor genes in the rooster epididymis during growth and Salmonella infection.

    Anastasiadou, M; Avdi, M; Michailidis, G

    2013-08-01

    The epididymis is an organ involved in the maturation, transport, and storage of sperm prior to ejaculation. As epididymis is exposed to a constant risk of inflammatory conditions that may lead to transient or permanent sterility, protection of this organ from pathogens is an essential aspect of reproductive physiology. The families of antimicrobial peptides β-defensins and the pattern-recognition receptors Toll-like (TLR) mediate innate immunity in various vertebrates including avian species. As rooster infertility is a major concern in the poultry industry, the objectives of this study were to determine the expression profile of the entire family of the avian β-defensins (AvBD) and TLR genes in the rooster epididymis, to investigate whether sexual maturation affects their epididymidal mRNA abundance and to determine the changes in their expression levels in response to Salmonella enteritidis (SE) infection in the epididymis of sexually mature roosters. RNA was extracted from the epididymis of healthy pubertal, sexually mature and aged birds, and from sexually mature SE infected birds. RT-PCR analysis revealed that 10 members of the AvBD and nine members of the TLR gene families were expressed in the epididymis. Quantitative real-time PCR analysis revealed that the epididymidal mRNA abundance of certain AvBD and TLR genes was developmentally regulated with respect to sexual maturation. SE infection resulted in a significant induction of AvBD 1, 9, 10, 12 and 14, as well as TLR 1-2, 2-1, 2-2, 4, 5 and 7 genes, in the epididymis of sexually mature roosters, compared to healthy birds of the same age. These findings provide strong evidence to suggest that the rooster epididymis is capable of initiating an inflammatory response to Salmonella, through activation of certain members of the AvBD and TLR gene families. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Synovial Fluid α-Defensin as a Biomarker for Peri-Prosthetic Joint Infection: A Systematic Review and Meta-Analysis.

    Li, Bin; Chen, Fei; Liu, Yi; Xu, Guokang

    Total joint arthroplasty (TJA) has been one of the most beneficial interventions for treating patients suffering from joint disorders. However, peri-prosthetic joint infection (PJI) is a serious complication that often accompanies TJA and the diagnosis of PJI is remains difficult. Questions remain regarding whether certain biomarkers can be valuable in the diagnosis of PJI. We conducted our systematic review by searching PubMed, Embase, Web of Science, the Cochrane Library, and Science Direct with the key words "periprosthetic joint infection," "synovial fluid," and "α-defensin." Studies that provided sufficient data to construct 2 × 2 contingency tables were chosen based on inclusion and exclusion criteria. The quality of included studies was assessed according to the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for the included studies. The summary receiver operating characteristic (SROC) curve and the area under the summary receiver operating characteristic (AUSROC) were used to evaluate the overall diagnostic performance. Eight studies were included in this systematic review. Among them four articles were included in meta-analysis. A total of 421 participants were studied in the meta-analysis. The pooled sensitivity, specificity, and DOR were 0.98 (95% confidence interval [CI]: 0.94-1.00), 0.97 (95% CI: 0.95-0.99), and 1095.49 (95% CI: 283.68.58-4230.45), respectively. The AUSROC was 0.9949 (standard error [SE] 0.0095). Synovial fluid α-defensin is a biomarker of high sensitivity and specificity for the diagnosis of PJI.

  1. Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses

    Tuladhar, E.

    2014-01-01

    Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses

    Era Tuladhar

    Abstract

    Human noroviruses are the leading cause of acute and outbreak associated gastroenteritis worldwide. The outbreaks

  2. Measurement and prediction of enteric methane emission

    Sejian, Veerasamy; Lal, Rattan; Lakritz, Jeffrey; Ezeji, Thaddeus

    2011-01-01

    The greenhouse gas (GHG) emissions from the agricultural sector account for about 25.5% of total global anthropogenic emission. While CO2 receives the most attention as a factor relative to global warming, CH4, N2O and chlorofluorocarbons (CFCs) also cause significant radiative forcing. With the relative global warming potential of 25 compared with CO2, CH4 is one of the most important GHGs. This article reviews the prediction models, estimation methodology and strategies for reducing enteric CH4 emissions. Emission of CH4 in ruminants differs among developed and developing countries, depending on factors like animal species, breed, pH of rumen fluid, ratio of acetate:propionate, methanogen population, composition of diet and amount of concentrate fed. Among the ruminant animals, cattle contribute the most towards the greenhouse effect through methane emission followed by sheep, goats and buffalos, respectively. The estimated CH4 emission rate per cattle, buffaloe, sheep and goat in developed countries are 150.7, 137, 21.9 and 13.7 (g/animal/day) respectively. However, the estimated rates in developing countries are significantly lower at 95.9 and 13.7 (g/animal/day) per cattle and sheep, respectively. There exists a strong interest in developing new and improving the existing CH4 prediction models to identify mitigation strategies for reducing the overall CH4 emissions. A synthesis of the available literature suggests that the mechanistic models are superior to empirical models in accurately predicting the CH4 emission from dairy farms. The latest development in prediction model is the integrated farm system model which is a process-based whole-farm simulation technique. Several techniques are used to quantify enteric CH4 emissions starting from whole animal chambers to sulfur hexafluoride (SF6) tracer techniques. The latest technology developed to estimate CH4 more accurately is the micrometeorological mass difference technique. Because the conditions under which

  3. [Enteral nutrition: reduction in the contamination risk].

    Montemerlo, H; Menéndez, A M; Marcenac, F; Floridia, J; Esteban, L; Barbaricca, M

    1996-01-01

    Enteral nutrition is used as a routine therapy in patients with caloric-protein malnutrition, severe dysphagia, major burns, intestinal resection, and enterocutaneous fistulae, as long as a portion of the digestive tract still has an active absorptive function. The administration takes place by means of surgical (ostomies) or non-surgical (nasogastric) tubes. In our country, a significant number of hospitalized patients with various diseases receive this type of nutrition. Given that the colonization of the digestive tract by hospital flora is the first step towards developing intra-hospital infections, the contamination implies serious risks. The objective of this study was to study the most appropriate conditions for the manufacturing, storage and administration of the mixture of nutrients of enteral nutrition, to guarantee nutrition with a lower contamination risk. This study was conducted by the Unit of Nutritional Assistance of the Mater Dei Clinic, by means of bacteriological controls, from January 1991 to December 1992, and in 1993 in which the work systematics were reviewed. The study was prospective, and those solutions whose bacteriological counts were lower than 100.000 colony forming units (CFU), and which showed an absence of enteropathological micro-organisms, were considered acceptable, and those solutions which had a bacteriological count greater than or equal to 100.000 CFU and or the presence of enteropathological micro-organisms, were considered unacceptable. During the first period, "usual working conditions", we analyzed the infra-structure, the personnel, the constituents, and the apparatus used in the manufacturing, for which 36 samples were studied at t0 (moment of preparation). Afterwards, in the second period "special working conditions", we analyzed the manufacturing procedures, the storage and the administration of 103 solutions, corresponding to 36 patients, taking samples at t0 and t24 (after 24 hours of preparing). In the first phase

  4. A systematic review of zoonotic enteric parasitic diseases among nomadic and pastoral people.

    Amber N Barnes

    Full Text Available Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water, sanitation, and hygiene practices and diet. While most communities are now sedentary, nomadic and pastoral populations still exist and experience unique exposure risks for acquiring zoonotic enteric parasites. Through this systematic review we sought to summarize published research regarding pathogens present in nomadic populations and to identify the risk factors for their infection.Using systematic review guidelines set forth by PRISMA, research articles were identified, screened and summarized based on exclusion criteria for the documented presence of zoonotic enteric parasites within nomadic or pastoral human populations. A total of 54 articles published between 1956 and 2016 were reviewed to determine the pathogens and exposure risks associated with the global transhumance lifestyle.The included articles reported more than twenty different zoonotic enteric parasite species and illustrated several risk factors for nomadic and pastoralist populations to acquire infection including; a animal contact, b food preparation and diet, and c household characteristics. The most common parasite studied was Echinococcosis spp. and contact with dogs was recognized as a leading risk factor for zoonotic enteric parasites followed by contact with livestock and/or wildlife, water, sanitation, and hygiene barriers, home slaughter of animals, environmental water exposures, household member age and sex, and consumption of unwashed produce or raw, unprocessed, or undercooked milk or meat.Nomadic and pastoral communities are at risk of infection with a variety of zoonotic enteric parasites due to their living environment, cultural and dietary traditions, and close relationship to animals. Global health efforts aimed at reducing the transmission of these animal-to-human pathogens must incorporate

  5. Gene expression demonstrates an immunological capacity of the human endolymphatic sac

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2015-01-01

    OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear...... was obtained. Multiple key elements of both the cellular and humoral innate immune system were expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and lactoferrin. CONCLUSIONS: The present data provides the first direct evidence of an immunological capacity of the human endolymphatic sac...... immunological entity of the inner ear. LEVEL OF EVIDENCE: N/A....

  6. Enter as an outsider: Teaching organizational humility.

    Clabby, John F

    2017-05-01

    The concept of cultural humility acknowledges the enormous task of becoming culturally competent by encouraging curiosity about the context within which others live. For physicians, this includes curiosity about the organizations in which they work as Outsiders in settings such as a new hospital or patients' homes. However, efforts to train healthcare professionals in cultural competence are often de-emphasized due to the pressure learners feel to acquire Medical Knowledge and clinical skills. Little time is devoted to address the significance of cultural humility for fully appreciating the experiences of others. Efforts to educate physicians-in-training about the cultural aspects of care require innovative approaches that help them recognize bias without provoking defensiveness. Enter as an Outsider is a highly focused activity which fosters a culturally humble approach to an often neglected problem, organizational bias. This article describes how cultural humility is explained to learners and small group activities are used to explore the thoughts and feelings of an organization's Insiders and Outsiders. This program relies on instructor self-disclosure to facilitate learning and on a video vignette from popular-culture media to illustrate being an Outsider in a healthcare setting. Participants in this training have improved their ability to recognize when they are Outsiders where they provide care. They have developed a better understanding that cultural humility in organizations is a gateway to providing quality care. They have begun the process of committing to respectfully learn from the organization's Insiders.

  7. Treatment of radiation enteritis: a comparison study

    Loiudice, T.A.; Lang, J.A.

    1983-01-01

    Twenty-four patients with severe radiation injury to the small bowel seen over a 4-year period were randomized to four treatment groups: 1) methylprednisolone 80 mg intravenously plus Vivonex-HN, 2 L/day po, 2) methylprednisolone 80 mg intravenously plus total parenteral nutrition, 2.5 L/day, 3) total parenteral nutrition, 2.5 L/day, and 4) Vivonex-HN, 2 L/day po. Patients received nothing by mouth except water in groups II and III, and only Vivonex-HN in groups I and IV. Patients were treated for 8-wk periods. Improvement was gauged by overall nutritional assessment measurements, nitrogen balance data and by radiological and clinical parameters. No significant difference between groups I, II, III, and IV could be found for age, sex, mean radiation dosage, time of onset after radiation therapy, or initial nutritional assessment data. Differences statistically could be found between groups II and III and I and IV regarding nutritional assessment data, nitrogen balance, radiographic and clinical parameters after therapy, with marked improvement noted in groups II and III. We conclude that a treatment regimen consisting of total parenteral nutrition and bowel rest is beneficial in the treatment of radiation enteritis. Methylprednisolone appears to enhance this effect and indeed, may be responsible for a longer lasting response

  8. Pathophysiology and surgical treatment for radiation enteritis

    Onodera, Hisashi; Park, Tae Bun; Hasegawa, Masato

    1993-01-01

    We analyzed 23 patients (5 males and 18 females, mean age 60) who had been operated on in our department for radiation enteritis. 1) These patients were divided into two types according to the time of surgery. Sixteen of 23 (79%) patients were operated on a median of 12 months after radiotherapy, while 7 (30%) underwent surgery more than 10 years later. 2) They were also divided according to the dominant symptoms. Fourteen of 23 (60%) complained of nausea and abdominal distension suggestive of small bowel injury, whereas 7 (30%) had tenesmus and anal bleeding indicating proctitis. Two patients developed perforative peritonitis. 3) The operations performed were as follows: extensive intestinal resection and anastomosis (13), pull-through procedure (3), rectal excision (2), ileostomy (3), by-pass operation (2). Two patients with peritonitis died despite open drainage. Nineteen intestinal anastomoses were all successfully performed. Patients who underwent extensive small bowel resection could resume ordinary daily life without symptoms. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowels followed by anastomosis of the disease-free ends, while rectal lesions are best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage. (author)

  9. Pathophysiology and surgical treatment for radiation enteritis

    Onodera, Hisashi; Park, Tae Bun; Hasegawa, Masato (Kyoto Univ. (Japan). Faculty of Medicine) (and others)

    1993-12-01

    We analyzed 23 patients (5 males and 18 females, mean age 60) who had been operated on in our department for radiation enteritis. (1) These patients were divided into two types according to the time of surgery. Sixteen of 23 (79%) patients were operated on a median of 12 months after radiotherapy, while 7 (30%) underwent surgery more than 10 years later. (2) They were also divided according to the dominant symptoms. Fourteen of 23 (60%) complained of nausea and abdominal distension suggestive of small bowel injury, whereas 7 (30%) had tenesmus and anal bleeding indicating proctitis. Two patients developed perforative peritonitis. (3) The operations performed were as follows: extensive intestinal resection and anastomosis (13), pull-through procedure (3), rectal excision (2), ileostomy (3), by-pass operation (2). Two patients with peritonitis died despite open drainage. Nineteen intestinal anastomoses were all successfully performed. Patients who underwent extensive small bowel resection could resume ordinary daily life without symptoms. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowels followed by anastomosis of the disease-free ends, while rectal lesions are best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage. (author).

  10. Enteral Nutrition in Pancreaticoduodenectomy: A Literature Review

    Salvatore Buscemi

    2015-04-01

    Full Text Available Pancreaticoduodenectomy (PD is considered the gold standard treatment for periampullory carcinomas. This procedure presents 30%–40% of morbidity. Patients who have undergone pancreaticoduodenectomy often present perioperative malnutrition that is worse in the early postoperative days, affects the process of healing, the intestinal barrier function and the number of postoperative complications. Few studies focus on the relation between enteral nutrition (EN and postoperative complications. Our aim was to perform a review, including only randomized controlled trial meta-analyses or well-designed studies, of evidence regarding the correlation between EN and main complications and outcomes after pancreaticoduodenectomy, as delayed gastric emptying (DGE, postoperative pancreatic fistula (POPF, postpancreatectomy hemorrhage (PPH, length of stay and infectious complications. Several studies, especially randomized controlled trial have shown that EN does not increase the rate of DGE. EN appeared safe and tolerated for patients after PD, even if it did not reveal any advantages in terms of POPF, PPH, length of stay and infectious complications.

  11. Chronic radiation enteritis: A community hospital experience

    Fenner, M.N.; Sheehan, P.; Nanavati, P.J.; Ross, D.S.

    1989-01-01

    A retrospective study was undertaken to evaluate the operative management of patients with chronic radiation enteropathy. Thirty-eight affected patients from 1974 to 1986 were reviewed. Patients with recurrent cancer responsible for symptoms were excluded. Seventy-one percent of patients presented with bowel obstruction. Twenty-one patients were treated with bowel resection, while 17 were treated with a bypass procedure or diverting ostomy alone. Overall morbidity was 45%, and postoperative mortality was 16%. Patients in the bypass group were significantly older than those in the resection group (70.3 vs. 55.5 years, P = .024), suggesting that age may have been a determinant of the procedure performed. In our study there was no difference in outcome based on preexisting vascular disease, tumor site, type of procedure performed, or radiation dose. We conclude that resection is the procedure of choice in cases of chronic radiation enteritis requiring surgery except in cases with dense adhesions when enteroenterostomal bypass is a viable alternative

  12. Osmolality and pH in handmade enteral diets used in domiciliary enteral nutritional therapy

    Gilberto Simeone HENRIQUES

    Full Text Available Abstract Patients who need prolonged domiciliary enteral nutritional therapy may benefit from handmade diets. However, the preparation of such diets might cause insecurity with regard to their nutritional composition and physical-chemical properties. Current study analyzes the osmolality and Hydrogen-Ion concentration (pH on handmade enteral diets. To this purpose, six formulas and two juices, prescribed on discharge from hospital, were analyzed physically and chemically. Osmolality and pH were respectively determined by cryoscopy and potentiometry. Most formulations were classified as isosmolar (with less than 400 mOsm/kg solvent, and only one was classified as slightly hyperosmolar, with rates ranging from 356.7 to 403.5 mOsm/kg solvent. On average, the standard formula presented higher osmolality than similar ones prepared for hyperglycemia. Among the juices, only one registered hyperosmolar concentration of 595.54 mOsm/kg solvent. All formulas presented pH rates classified as low acidity, ranging between 6.1 and 6.6, while the two juices had the lowest results, 4.73 and 4.66 each. The blend of ingredients used in handmade formulas and juices studied presented acceptable osmolality and pH rates for a safe administration and absence of gastrointestinal complications. Data showed here are consistent with an appropriate and healthy diet and contributed towards success in domiciliary enteral nutritional therapy.

  13. [Sensory evaluation of enteral nutritional supplements].

    Granell Vidal, Lina; Sánchez Juan, Carlos; Alfonso García, Antonio

    2014-07-01

    Enteral nutrition (EN) is indicated in patients who, although they may not eat enough food, maintain a sufficient function to receive, digest and absorb nutrients digestive system. Oral Nutritional Supplements (SON) are nutritionally complete or incomplete formulas (depending on whether or not provide all the nutrients needed to serve as the sole source of nutrients), which supplement inadequate oral diet. This study aims to evaluate the organoleptic characteristics of hyperproteic, normoproteic and fiber-enriched oral SON. SON test, carried out at the Department of Endocrinology and Nutrition Consortium Hospital General Universitario de Valencia from October 2012 to February 2013. 137 SON were evaluated in total, of which 47 were hyperproteic, 46 normoproteic and 44 enriched in fiber. Of the SON evaluated in the group of hyperproteic the following 3 SON obtained the best scores: Fresenius Prot Energy Drink® (21,27, vanilla flavor), Avant Standard Nut® (20.3 , strawberry flavor) and Resource® Protein (20.01, chocolate flavor) In the group of normoproteic SON the 3 best rated were: Ensure Plus® (22.3, banana flavor), Ensure Plus® (21.9, peach flavor) and Fresubin Energy Drink® (21, strawberry flavor) In the group of fiber-enriched the 3 SON most appreciated were: 2 Kcal Fresubin Fibre Drink® (23.78, vanilla flavor), Ensure Plus® TwoCal (22.9, banana flavor) and Fortimel Compact® (21.5, strawberry flavor) The study aims to guide clinicians on what SON may be more acceptable to the patient, so that the SON serve their purpose and restore or improve nutritional status, as the SON intervention is safe and cost - effective, since they improve both the functionality and quality of life. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  14. Toxin-mediated effects on the innate mucosal defenses: implications for enteric vaccines

    Glenn, Gregory M; Francis, David H; Danielsen, E Michael

    2009-01-01

    mucosal barrier as a key step in enteric pathogen survival. We review key observations relevant to the roles of LT and cholera toxin in protective immunity and the effects of these toxins on innate mucosal defenses. We suggest either that toxin-mediated fluid secretion mechanically disrupts the mucus...... layer or that toxins interfere with innate mucosal defenses by other means. Such a breach gives pathogens access to the enterocyte, leading to binding and pathogenicity by enterotoxigenic E. coli (ETEC) and other organisms. Given the common exposure to LT(+) ETEC by humans visiting or residing...... unexpectedly broad protective effects against LT(+) ETEC and mixed infections when using a toxin-based enteric vaccine. If toxins truly exert barrier-disruptive effects as a key step in pathogenesis, then a return to classic toxin-based vaccine strategies for enteric disease is warranted and can be expected...

  15. Modulation of intestinal inflammation by minimal enteral nutrition with amniotic fluid in preterm pigs

    Østergaard, Mette Viberg; Bering, Stine Brandt; Jensen, Michael Ladegaard

    2014-01-01

    Background: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder, associated with the difficult transition from parenteral to enteral feeding after preterm birth. We hypothesized that minimal enteral nutrition (MEN) with amniotic fluid (AF), prior to enteral formula feeding, would...... improve resistance to NEC in preterm pigs. Methods: Experiment 1: IEC-6 cells were incubated with porcine (pAF) and human AF (hAF) to test AF-stimulated enterocyte proliferation and migration in vitro. Experiment 2: Cesarean-delivered, preterm pigs were fed parenteral nutrition and MEN with pAF, h...... fed AF as MEN, but NEC incidences were similar (NEC-pAF) or increased (NEC-hAF) compared with controls. Conclusions: Intake of pAF or hAF improved body growth and modulated intestinal inflammatory cytokines during a period of parenteral nutrition, but did not protect against later formula-induced NEC...

  16. Environmental change and enteric zoonoses in New Zealand: a systematic review of the evidence.

    Lal, Aparna; Lill, Adrian W T; Mcintyre, Mary; Hales, Simon; Baker, Michael G; French, Nigel P

    2015-02-01

    To review the available evidence that examines the association between climatic and agricultural land use factors and the risks of enteric zoonoses in humans and consider information needs and possible pathways of intervention. The electronic databases PubMed, Web of Science and Embase and government websites were searched systematically for published literature that investigated the association of climatic and/or agricultural exposures with the incidence of the four most common enteric zoonotic diseases in New Zealand (campylobacteriosis, salmonellosis, cryptosporidiosis and giardiasis). Results The 16 studies in the review demonstrated significant associations between climate, agricultural land use and enteric disease occurrence. The evidence suggests that enteric disease risk from environmental reservoirs is pathogen specific. In some rural regions, environmental pathogen load is considerable, with multiple opportunities for zoonotic transmission. Enteric disease occurrence in NZ is associated with climate variability and agricultural land use. However, these relationships interact with demographic factors to influence disease patterns. Improved understanding of how environmental and social factors interact can inform effective public health interventions under scenarios of projected environmental change. © 2014 Public Health Association of Australia.

  17. The survival and inactivation of enteric viruses on soft surfaces: A systematic review of the literature.

    Yeargin, Thomas; Buckley, David; Fraser, Angela; Jiang, Xiuping

    2016-11-01

    Worldwide, enteric viruses are the main cause of acute gastroenteritis. In humans, these viruses spread via person-to-person contact, food, water, and/or the environment. Their survival and inactivation on hard surfaces have been extensively studied; however, nonlaunderable soft surfaces, such as upholstery and carpet, have received little attention. The aim of this systematic review was to determine factors that influence the survival and inactivation of enteric viruses on nonlaunderable soft surfaces. EBSCO and Web of Science were searched for experimental studies published between 1965 and 2015 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods. Titles and abstracts were screened using 3 eligibility criteria. The quality of all study methods was also assessed. Our search yielded 12 articles. Viruses survived between 0 hours and 140 days depending on surface and environment conditions. Virus survival was influenced by temperature, relative humidity, organic content, and deposition method. A variety of chemistries were tested across studies and were shown to have a varied effect on enteric viruses. Chlorine, glutaraldehyde, vaporous ozone, and hydrogen peroxide were the most efficacious against enteric viruses (> 3-log reduction). Environmental factors, such as temperature and relative humidity, can influence survival of enteric viruses on nonlaunderable soft surfaces. The efficacy of liquid and vaporous chemistries are associated with surface and virus type. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Coronavirus–associated enteritis in a quail farm

    Antonio Camarda

    2010-01-01

    Full Text Available An enteric syndrome observed in semi-intensively reared quails is described. The affected birds showed depression, severe diarrhoea and dehydration. The mortality occurred particularly in young birds. At necropsy, the prominent lesion was catarrhal enteritis. Laboratory investigations demonstrated the presence of coronavirus in the gut of dead animals. No additional pathogens were detected. To our knowledge, this is the first evidence for the presence of CoVs in quail with enteritis.

  19. Enteral feeding pumps: efficacy, safety, and patient acceptability

    White H

    2014-08-01

    Full Text Available Helen White, Linsey King Nutrition and Dietetic Group, School of Health and Wellbeing, Faculty Health and Social Science, Leeds Metropolitan University, Leeds, United Kingdom Abstract: Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accuracy, safety, and consistency with which enteral feed pump systems dispense nutritional formulae are important determinants of their use and acceptability. Enteral feed pump safety has received increased interest in recent years as enteral pumps are used across hospital and home settings. Four areas of enteral feed pump safety have emerged: the consistent and accurate delivery of formula; the minimization of errors associated with tube misconnection; the impact of continuous feed delivery itself (via an enteral feed pump; and the chemical composition of the casing used in enteral feed pump manufacture. The daily use of pumps in delivery of enteral feeds in a home setting predominantly falls to the hands of parents and caregivers. Their understanding of the use and function of their pump is necessary to ensure appropriate, safe, and accurate delivery of enteral nutrition; their experience with this is important in informing clinicians and manufacturers of the emerging needs and requirements of this diverse patient population. The review highlights current practice and areas of concern and establishes our current knowledge in this field. Keywords: nutrition, perceptions, experience

  20. Impact of enteral protein supplementation in premature infants

    Barrus DM

    2012-06-01

    Full Text Available David M Barrus1, Joann Romano-Keeler2, Christopher Carr3, Kira Segebarth4, Betty Claxton2, William F Walsh2, Paul J Flakoll51Department of Neonatology, Saint Francis Hospital–Bartlett, Memphis, TN, 2Department of Pediatrics, Vanderbilt Medical Center, Nashville, TN, 3Department of Surgery, Naval Hospital Bremerton, Bremerton, WA, 4Pediatric and Diabetes Specialists, Carolinas Medical Center, Charlotte, NC, 5Department of Surgery, Vanderbilt Medical Center, Nashville, TN, USAObjective: The quantity of enteral protein supplementation required by premature infants to optimize growth has not been determined. This study compares the growth of premature infants fed the current standard intake of protein (3.5 g/kg/day with the growth of those fed a higher amount (4.0 g/kg/day.Study design: Fifty-two infants <1500 g and <33 weeks gestational age participated in a blinded, single-center, prospective randomized control trial to compare growth between two groups of different protein-intake levels. Primary outcomes were average daily weight gain (g/kg/day, head-circumference (cm/kg/week and linear growth velocity (cm/kg/week. Secondary outcomes were serum indices of protein tolerance and plasma amino acid concentrations.Results: Infants receiving higher amounts of protein had higher rates of growth for body weight (18.2 ± 0.7 versus 16.2 ± 1.0 g/kg/day; P < 0.05 and head circumference (0.87 ± 0.08 versus 0.62 ± 0.07 cm/kg/week; P < 0.05, with no differences in blood protein or plasma amino acid concentrations. Length of hospital stay was 14 days shorter for the higher-protein group (51.4 ± 4.0 versus 65.9 ± 6.3 days.Conclusion: Increasing premature infant enteral protein supplementation from a calculated intake of 3.5–4.0 g/kg/day improved growth in a safe manner.Keywords: human milk, human milk fortifier, growth, low birth weight

  1. Two Contrasting Failure Modes of Enteric Coated Beads.

    Shi, Galen H; Dong, Xia; Lytle, Michelle; Kemp, Craig A J; Behme, Robert J; Hinds, Jeremy; Xiao, Zhicheng

    2018-04-09

    This study aimed to elucidate the mechanisms and kinetics of coating failure for enteric coated beads exposed to high-humidity conditions at different storage temperatures. Enteric coated beads were placed on high-humidity conditions (75 to 98% relative humidity (RH)) in the temperature range of 5 to 40°C. These stability samples of beads were tested for acid dissolution and water activity and also analyzed with SEM, X-ray CT, and DMA. Exposure of enteric coated beads to high humidity led to increased gastric release of drug which eventually failed the dissolution specification. SEM showed visible cracks on the surface of beads exposed to 5°C/high humidity and fusion of enteric beads into agglomerates at 40°C/high humidity. In a non-destructive time elapse study, X-ray CT demonstrated swelling of microcrystalline cellulose cores, crack initiation, and propagation through the API layer within days under 5°C/98% RH storage conditions and ultimately fracture through the enteric coating. DMA data showed a marked reduction in T g of the enteric coating materials after exposure to humidity. At 5°C/high humidity, the hygroscopic microcrystalline cellulose core absorbed moisture leading to core swelling and consequent fracture through the brittle API and enteric layers. At 40°C (high humidity) which is above the T g of the enteric polymer, enteric coated beads coalesced into agglomerates due to melt flow of the enteric coating. We believe it is the first report on two distinct failure models of enteric coated dosage forms.

  2. Dieta enteral prescrita versus dieta infundida Prescribed enteral diet versus infused diet

    Silvana Aparecida Ribeiro Simões

    2017-07-01

    Full Text Available Objetivo: Avaliar o volume prescrito de dieta enteral versus o volume infundido, identificando as causas de interrupção da dieta e os gastos gerados por essas interrupções. Métodos: Estudo observacional, com pacientes adultos e idosos, recebendo nutrição enteral em um hospital particular de São Paulo. A coleta de dados foi realizada por meio de prontuário eletrônico. Resultados: O volume infundido foi significantemente menor que o volume prescrito, nos cinco dias de acompanhamento, em toda a amostra. A principal intercorrência na administração da dieta foi a diarreia. Os gastos com a não administração da dieta somam 41,4% do valor despendido para esse serviço. Conclusão: Este estudo contribui para a atuação e desempenho do nutricionista em conjunto com a Equipe Multidisciplinar em Terapia Nutricional visando a melhora do paciente.

  3. Complications relating to enteral and parenteral nutrition in trauma ...

    Objectives: The aim of the study was to compare the incidence of complications in patients receiving enteral and parenteral nutrition (PN), and review how the early initiation of enteral feeding and early achievement of caloric goal would affect the incidence of complications. Design: The design was a retrospective audit of ...

  4. Enteric pathogen modification by anaecic earthworm, Lampito Mauritii

    The biosolids from municipal wastewater treatment plant contains several enteric microbial pathogens, predominantly Salmonella and Escherichia species in the range of 15-18 x 104 CFU/g and 11-12 x 104 CFU/g respectively. The present study investigates the influence of earthworm, Lampito mauritii on enteric pathogen ...

  5. Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients.

    Pingleton, S K; Hadzima, S K

    1983-01-01

    The incidence of upper gastrointestinal (GI) bleeding in mechanically ventilated ICU patients receiving enteral alimentation was reviewed and compared to bleeding occurring in ventilated patients receiving prophylactic antacids or cimetidine. Of 250 patients admitted to our ICU during a 1-yr time period, 43 ventilated patients were studied. Patients in each group were comparable with respect to age, respiratory diagnosis, number of GI hemorrhage risk factors, and number of ventilator, ICU, and hospital days. Twenty-one patients had evidence of GI bleeding. Fourteen of 20 patients receiving antacids and 7 of 9 patients receiving cimetidine had evidence of GI bleeding. No bleeding occurred in 14 patients receiving enteral alimentation. Complications of enteral alimentation were few and none required discontinuation of enteral alimentation. Our preliminary data suggest the role of enteral alimentation in critically ill patients may include not only protection against malnutrition but also protection against GI bleeding.

  6. Spectral analysis of HIV seropositivity among migrant workers entering Kuwait

    Mohammad Hameed GHH

    2008-03-01

    Full Text Available Abstract Background There is paucity of published data on human immunodeficiency virus (HIV seroprevalence among migrant workers entering Middle-East particularly Kuwait. We took advantage of the routine screening of migrants for HIV infection, upon arrival in Kuwait from the areas with high HIV prevalence, to 1 estimate the HIV seroprevalence among migrant workers entering Kuwait and to 2 ascertain if any significant time trend or changes had occurred in HIV seroprevalence among these migrants over the study period. Methods The monthly aggregates of daily number of migrant workers tested and number of HIV seropositive were used to generate the monthly series of proportions of HIV seropositive (per 100,000 migrants over a period of 120 months from January 1, 1997 to December 31, 2006. We carried out spectral analysis of these time series data on monthly proportions (per 100,000 of HIV seropositive migrants. Results Overall HIV seroprevalence (per 100,000 among the migrants was 21 (494/2328582 (95% CI: 19 -23, ranging from 11 (95% CI: 8 – 16 in 2003 to 31 (95% CI: 24 -41 in 1998. There was no discernable pattern in the year-specific proportions of HIV seropositive migrants up to 2003; in subsequent years there was a slight but consistent increase in the proportions of HIV seropositive migrants. However, the Mann-Kendall test showed non-significant (P = 0.741 trend in de-seasonalized data series of proportions of HIV seropositive migrants. The spectral density had a statistically significant (P = 0.03 peak located at a frequency (radians 2.4, which corresponds to a regular cycle of three-month duration in this study. Auto-correlation function did not show any significant seasonality (correlation coefficient at lag 12 = – 0.025, P = 0.575. Conclusion During the study period, overall a low HIV seroprevalence (0.021% was recorded. Towards the end of the study, a slight but non-significant upward trend in the proportions of HIV seropositive

  7. Postoperative ileus involves interleukin-1 receptor signaling in enteric glia.

    Stoffels, Burkhard; Hupa, Kristof Johannes; Snoek, Susanne A; van Bree, Sjoerd; Stein, Kathy; Schwandt, Timo; Vilz, Tim O; Lysson, Mariola; Veer, Cornelis Van't; Kummer, Markus P; Hornung, Veit; Kalff, Joerg C; de Jonge, Wouter J; Wehner, Sven

    2014-01-01

    Postoperative ileus (POI) is a common consequence of abdominal surgery that increases the risk of postoperative complications and morbidity. We investigated the cellular mechanisms and immune responses involved in the pathogenesis of POI. We studied a mouse model of POI in which intestinal manipulation leads to inflammation of the muscularis externa and disrupts motility. We used C57BL/6 (control) mice as well as mice deficient in Toll-like receptors (TLRs) and cytokine signaling components (TLR-2(-/-), TLR-4(-/-), TLR-2/4(-/-), MyD88(-/-), MyD88/TLR adaptor molecule 1(-/-), interleukin-1 receptor [IL-1R1](-/-), and interleukin (IL)-18(-/-) mice). Bone marrow transplantation experiments were performed to determine which cytokine receptors and cell types are involved in the pathogenesis of POI. Development of POI did not require TLRs 2, 4, or 9 or MyD88/TLR adaptor molecule 2 but did require MyD88, indicating a role for IL-1R1. IL-1R1(-/-) mice did not develop POI; however, mice deficient in IL-18, which also signals via MyD88, developed POI. Mice given injections of an IL-1 receptor antagonist (anakinra) or antibodies to deplete IL-1α and IL-1β before intestinal manipulation were protected from POI. Induction of POI activated the inflammasome in muscularis externa tissues of C57BL6 mice, and IL-1α and IL-1β were released in ex vivo organ bath cultures. In bone marrow transplantation experiments, the development of POI required activation of IL-1 receptor in nonhematopoietic cells. IL-1R1 was expressed by enteric glial cells in the myenteric plexus layer, and cultured primary enteric glia cells expressed IL-6 and the chemokine monocyte chemotactic protein 1 in response to IL-1β stimulation. Immunohistochemical analysis of human small bowel tissue samples confirmed expression of IL-1R1 in the ganglia of the myenteric plexus. IL-1 signaling, via IL-1R1 and MyD88, is required for development of POI after intestinal manipulation in mice. Agents that interfere with

  8. Systemic Induction of the Defensin and Phytoalexin Pisatin Pathways in Pea (Pisum sativum against Aphanomyces euteiches by Acetylated and Nonacetylated Oligogalacturonides

    Sameh Selim

    2017-06-01

    Full Text Available Oligogalacturonides (OGs are known for their powerful ability to stimulate the plant immune system but little is known about their mode of action in pea (Pisum sativum. In the present study, we investigated the elicitor activity of two fractions of OGs, with polymerization degrees (DPs of 2–25, in pea against Aphanomyces euteiches. One fraction was nonacetylated (OGs − Ac whereas the second one was 30% acetylated (OGs + Ac. OGs were applied by injecting the upper two rachises of the plants at three- and/or four-weeks-old. Five-week-old roots were inoculated with 105 zoospores of A. euteiches. The root infection level was determined at 7, 10 and 14 days after inoculation using the quantitative real-time polymerase chain reaction (qPCR. Results showed significant root infection reductions namely 58, 45 and 48% in the plants treated with 80 µg OGs + Ac and 59, 56 and 65% with 200 µg of OGs − Ac. Gene expression results showed the upregulation of genes involved in the antifungal defensins, lignans and the phytoalexin pisatin pathways and a priming effect in the basal defense, SA and ROS gene markers as a response to OGs. The reduction of the efficient dose in OGs + Ac is suggesting that acetylation is necessary for some specific responses. Our work provides the first evidence for the potential of OGs in the defense induction in pea against Aphanomyces root rot.

  9. Evaluation of porcine beta defensins-1 and -2 as antimicrobial peptides for liquid-stored boar semen: Effects on bacterial growth and sperm quality.

    Puig-Timonet, Adrià; Castillo-Martín, Miriam; Pereira, Barbara A; Pinart, Elisabeth; Bonet, Sergi; Yeste, Marc

    2018-04-15

    The present study evaluated whether two different antimicrobial peptides (AMP): porcine beta defensins-1 (PBD1) and -2 (PBD2) at three concentrations (1.5 μM, 3 μM and 5 μM) could be a suitable alternative to antibiotics in liquid-stored boar semen. Two separate experiments were conducted with liquid-stored boar semen preserved at 17 °C for 9-10 days. In the first one, we evaluated the impact of adding three concentrations of each AMP on the bacterial growth and sperm quality of boar semen stored for 10 days. In the second experiment, the ability of these AMPs to control bacterial growth was determined over a 9-day period, following artificial inoculation with Escherichia coli at 10 7 and 10 8  CFU mL -1 . In both experiments, sperm viability was assessed through flow cytometry, sperm motility was determined with Computer Assisted Sperm Analysis (CASA) and the inhibitory effect on microbial growth was evaluated by bacteria culture on Luria Bertani agar. PBD1 and PBD2 were found to significantly (P extenders for boar semen at a concentration of 3 μM, but do not completely control all bacterial growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

    Brun, Paola; Qesari, Marsela; Marconi, Peggy C; Kotsafti, Andromachi; Porzionato, Andrea; Macchi, Veronica; Schwendener, Reto A; Scarpa, Marco; Giron, Maria C; Palù, Giorgio; Calistri, Arianna; Castagliuolo, Ignazio

    2018-01-01

    Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection

  11. Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment

    Paola Brun

    2018-03-01

    Full Text Available Herpes Simplex Virus type 1 (HSV-1, a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2 to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i liposomes containing dichloromethylene bisphosphonic acid (clodronate to deplete tissue macrophages, (ii CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1

  12. Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

    Tsujikawa, T; Ohta, N; Nakamura, T; Yasuoka, T; Satoh, J; Fukunaga, T; Itohi, A; Uda, K; Ihara, T; Andoh, A; Sasaki, M; Fujiyama, Y; Bamba, T

    2001-10-01

    Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to reduce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis.

  13. Cellular changes in the enteric nervous system during ageing.

    Saffrey, M Jill

    2013-10-01

    The intrinsic neurons of the gut, enteric neurons, have an essential role in gastrointestinal functions. The enteric nervous system is plastic and continues to undergo changes throughout life, as the gut grows and responds to dietary and other environmental changes. Detailed analysis of changes in the ENS during ageing suggests that enteric neurons are more vulnerable to age-related degeneration and cell death than neurons in other parts of the nervous system, although there is considerable variation in the extent and time course of age-related enteric neuronal loss reported in different studies. Specific neuronal subpopulations, particularly cholinergic myenteric neurons, may be more vulnerable than others to age-associated loss or damage. Enteric degeneration and other age-related neuronal changes may contribute to gastrointestinal dysfunction that is common in the elderly population. Evidence suggests that caloric restriction protects against age-associated loss of enteric neurons, but recent advances in the understanding of the effects of the microbiota and the complex interactions between enteric ganglion cells, mucosal immune system and intestinal epithelium indicate that other factors may well influence ageing of enteric neurons. Much remains to be understood about the mechanisms of neuronal loss and damage in the gut, although there is evidence that reactive oxygen species, neurotrophic factor dysregulation and/or activation of a senescence associated phenotype may be involved. To date, there is no evidence for ongoing neurogenesis that might replace dying neurons in the ageing gut, although small local sites of neurogenesis would be difficult to detect. Finally, despite the considerable evidence for enteric neurodegeneration during ageing, and evidence for some physiological changes in animal models, the ageing gut appears to maintain its function remarkably well in animals that exhibit major neuronal loss, indicating that the ENS has considerable

  14. Pediatric Enteric Feeding Techniques: Insertion, Maintenance, and Management of Problems

    Nijs, Els L. F.; Cahill, Anne Marie

    2010-01-01

    Enteral feeding is considered a widespread, well-accepted means of delivering nutrition to adults and children who are unable to consume food by mouth or who need support in maintaining adequate nutrition for a variety of reasons, including acute and chronic disease states. Delivery of enteral feeding to nutritionally deprived patients may be achieved by several means. In this article, the indications and insertion of enteral access in children will be reviewed. In addition, common complications and management of problems will be discussed.

  15. Investigation of the effects of oleuropein rich diet on rat enteric bacterial flora.

    Kiraz, A; Simsek, T; Tekin, S Z; Elmas, S; Tekin, M; Sahin, H; Altinisik, H B; Pala, C

    2016-01-01

    Oleuropein is a phenolic compound of olive leaves. Enteric bacterial flora is very important for human health and diet is a directly affecting factor of enteric bacterial flora composition. In this study, it was hypothesized that oleuropein could reduce total aerobic bacterial count in rat caecal flora. Twenty adult, male, Wistar albino rats were randomly divided into two groups. Group C (n=10) was fed with standard rat chow and water for 30 days. Group O (n=10) received olive leaf extract 20 mg/kg/day by intragastric gavage in addition to standard rat chow and water for 30 days. One gram of caecal content was collected from each rat and then consecutive 10-fold serial dilutions were prepared with a final concentration of 10-8. Then 0.1 ml of each dilution were spread onto the surfaces of Plate Count Agar and Violet Red Bile Glucose Agar to enumerate the aerobic enteric bacteria. Total aerobic bacterial counts of Group O were significantly lower than of Group C in all agar plates inoculated with ceacal samples for every dilution (pbacterial translocation by reducing enteric bacterial counts (Tab. 1, Ref. 32).

  16. Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation.

    Taub, Amy; Bucay, Vivian; Keller, Gregory; Williams, Jay; Mehregan, Darius

    2018-04-01

    Anti-aging strategies utilizing stem cells are in the forefront. Alpha and beta defensins are natural immune peptides that have been shown to activate an LGR6-positive stem cell locus in the hair follicle, identified as the source of most new epidermal cells during acute wound healing. We investigated the ability of biomimetic alpha and beta defensin molecules, supplemented with supportive cosmetic ingredients, formulated into three skin care products, at improving the structure and function of aging skin. A participant- and investigator -blinded, placebo-controlled, multi-center trial was performed in outpatient settings. Forty-four healthy female subjects, aged 41-71 years, skin types I-V, completed the study with 2/3 receiving full formula and 1/3 receiving the placebo formula. A skin care regimen of 3 products (serum, cream, and mask) containing alpha-defensin 5 and beta-defensin 3, and other cosmetic ingredients, was applied to the face, post-auricular, and neck skin two times per day for 12 weeks in those receiving full formula, whereas the placebo group received the identically packaged regimen without the active ingredients. Methods of evaluation included histopathology and immunohistochemistry (7 subjects), clinical evaluation of pores, superficial and deep wrinkles based on Griffiths scale, and high-resolution photography (all subjects). In addition, a subset of 15 patients were evaluated with the QuantifiCare system (3-dimensional imaging and skin care scores for evenness, pores, oiliness) and Cortex measurements (high-resolution skin ultrasound, TEWL, elasticity, color, and hydration). Data points for evaluation included baseline, 6 weeks, and 12 weeks. All patients used the same sunscreen and cleanser, which was provided to them. The full formula regimen caused a significantly (P equals 0.027) increased thickness of the epidermis as seen in histology, not seen in the placebo group, with no signs of inflammation. No excessive cell proliferation was

  17. Communication Skill Attributes Needed for Vocational Education enter The Workplace

    Wahyuni, L. M.; Masih, I. K.; Rejeki, I. N. Mei

    2018-01-01

    Communication skills are generic skills which need to be developed for success in the vocational education entering the workforce. This study aimed to discover the attributes of communication skill considered important in entering the workforce as perceived by vocational education students. The research was conducted by survey method using questionnaire as data collecting tool. The research population is final year student of D3 Vocational education Program and D4 Managerial Vocational education in academic year 2016/2017 who have completed field work practice in industry. The sampling technique was proportional random sampling. Data were analyzed with descriptive statistics and independent sampel t-test. Have ten communication skills attributes with the highest important level required to enter the workplace as perceived by the vocational education diploma. These results indicate that there was the same need related communication skills to enter the workforce

  18. High enteric bacterial contamination of drinking water in Jigjiga city ...

    unhcc

    Key words: Contamination, drinking water, households, enteric bacteria, Jigjiga. Introduction. Water safety ... regular sanitary checks for un-chlorinated water (9). Because of this ... 238, considering 5% non-response rate. All kebeles have.

  19. Problems experienced by women re-entering the education profession

    Problems experienced by women re-entering the education profession: a South ... in maternity benefits, as well as the introduction of paternity and childcare leave, should be introduced to assist women educators to combine work and family ...

  20. Parenteral and Early Enteral Feeding in Patients with Colonic Tumor

    O. A. Malkov

    2008-01-01

    Full Text Available Objective: to provide evidence whether it is expedient to use an early enteral feeding protocol in patients with colonic malignancies in the postoperative period to prevent and to correct hemodynamic disorders, oxygen imbalance, and malnutrition. Subjects and methods. A hundred patients (61 males and 39 females aged 66.2±5.0 years, who had Stages 2—3 colonic malignancies, were examined. Two algorithms of postoperative management were analyzed using the traditional diet and early enteral feeding. Results. The early enteral feeding protocol improves central hemodynamics and oxygen and nutritional status, prevents moderate protein-energy deficiency in the early postoperative period and reduces the number of complications and fatal outcomes in patients with colonic malignancies. Key words: malignancies, malnutrition, hemo-dynamics, oxygen status, enteral feeding.

  1. Nurses' Competency and Challenges in Enteral feeding in the ...

    Studies have emphasised the role of nurses in nutritional support. .... Ethical consideration. The study was ... Mann-Whitney U test was applied to make associations ..... based guidelines and critical care nurses knowledge of enteral feeding.

  2. Environmental enteric dysfunction is associated with altered bile acid metabolism

    Environmental enteric dysfunction (EED), a clinically asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, and increased gut permeability, is common among children in developing countries. Because of abnormal gut mucosa and altered gut microbiome, EED coul...

  3. Emerging antibiotic resistant enteric bacterial flora among food ...

    Emerging antibiotic resistant enteric bacterial flora among food animals in Abeokuta, Nigeria. ... Nigerian Journal of Animal Production ... Bacterial resistance to antibiotic in food animals is an emerging public health concern as a result of ...

  4. Expression of apoplast-targeted plant defensin MtDef4.2 confers resistance to leaf rust pathogen Puccinia triticina but does not affect mycorrhizal symbiosis in transgenic wheat.

    Kaur, Jagdeep; Fellers, John; Adholeya, Alok; Velivelli, Siva L S; El-Mounadi, Kaoutar; Nersesian, Natalya; Clemente, Thomas; Shah, Dilip

    2017-02-01

    Rust fungi of the order Pucciniales are destructive pathogens of wheat worldwide. Leaf rust caused by the obligate, biotrophic basidiomycete fungus Puccinia triticina (Pt) is an economically important disease capable of causing up to 50 % yield losses. Historically, resistant wheat cultivars have been used to control leaf rust, but genetic resistance is ephemeral and breaks down with the emergence of new virulent Pt races. There is a need to develop alternative measures for control of leaf rust in wheat. Development of transgenic wheat expressing an antifungal defensin offers a promising approach to complement the endogenous resistance genes within the wheat germplasm for durable resistance to Pt. To that end, two different wheat genotypes, Bobwhite and Xin Chun 9 were transformed with a chimeric gene encoding an apoplast-targeted antifungal plant defensin MtDEF4.2 from Medicago truncatula. Transgenic lines from four independent events were further characterized. Homozygous transgenic wheat lines expressing MtDEF4.2 displayed resistance to Pt race MCPSS relative to the non-transgenic controls in growth chamber bioassays. Histopathological analysis suggested the presence of both pre- and posthaustorial resistance to leaf rust in these transgenic lines. MtDEF4.2 did not, however, affect the root colonization of a beneficial arbuscular mycorrhizal fungus Rhizophagus irregularis. This study demonstrates that the expression of apoplast-targeted plant defensin MtDEF4.2 can provide substantial resistance to an economically important leaf rust disease in transgenic wheat without negatively impacting its symbiotic relationship with the beneficial mycorrhizal fungus.

  5. Quantification of gut lesions in a subclinical necrotic enteritis model

    Gholamiandehkordi, Ahmad R.; Timbermont, Leen; Lanckriet, Anouk

    2007-01-01

    Currently Clostridium perfringens-induced necrotic enteritis is a major problem in broiler flocks. In the present study, broilers were inoculated with a combination of Eimeria maxima or overdose coccidial vaccine (one inoculation) with C. perfringens (repeated inoculations). Single C. perfringens...... in combination with multiple oral C. perfringens inoculations is a suitable model for necrotic enteritis without inducing mortality of the animals. C. perfringens and Eimeria act synergistically in inducing grossly visible gut damage....

  6. Antimicrobial effect of Malaysian vegetables against enteric bacteria

    Hassanain Al-Talib

    2016-03-01

    Conclusions: Garlic had excellent antimicrobial effects against enteric bacteria and was recommended to be given to patients with gastroenteritis. The other vegetables (pennywort, mint, parsley and celery showed no inhibitory effects on enteric bacteria but still can be used for its richness in vitamins and fibers. The performance of the well diffusion method was better than that of the disc diffusion method in detecting the antibacterial effects of green vegetables.

  7. Antibiotic-Resistant Enteric Bacteria in Environmental Waters

    Lisa M. Casanova

    2016-11-01

    Full Text Available Sources of antibiotic resistant organisms, including concentrated animal feeding operations (CAFOs, may lead to environmental surface and groundwater contamination with resistant enteric bacteria of public health concern. The objective of this research is to determine whether Salmonella, Escherichia coli, Yersinia enterocolitica, and enterococci resistant to clinically relevant antibiotics are present in surface and groundwater sources in two eastern North Carolina counties, Craven and Wayne. 100 surface and groundwater sites were sampled for Salmonella, E. coli, and enterococci, and the bacteria isolated from these samples were tested for susceptibility to clinically relevant antibiotics. Salmonella were detected at low levels in some surface but not groundwater. E. coli were in surface waters but not ground in both counties. Enterococci were present in surface water and a small number of groundwater sites. Yersinia was not found. Bacterial densities were similar in both counties. For Salmonella in surface water, the most frequent type of resistance was to sulfamethoxazole. There was no ciprofloxacin resistance. There were a few surface water E. coli isolates resistant to chloramphenicol, gentamicin, and ampicillin. Enterococci in surface water had very low levels of resistance to vancomycin, chloramphenicol, ampicillin, and streptomycin. E. coli and enterococci are present more frequently and at higher levels in surface water than Salmonella, but groundwater contamination with any of these organisms was rare, and low levels of resistance can be found sporadically. Resistant bacteria are relatively uncommon in these eastern N.C. surface and groundwaters, but they could pose a risk of human exposure via ingestion or primary contact recreation.

  8. [Biological evaluation of a protein mixture intended for enteral nutrition].

    Meneses, J Olza; Foulquie, J Porres; Valero, G Urbano; de Victoria, E Martínez; Hernández, A Gil

    2008-01-01

    Enteral nutrition is the best way to feed or supplement the diet when gastrointestinal tract functions of patients are partially or totally preserved. Whenever total enteral nutrition is needed, it represents the only source of nutrients for patients. Thus, it is mandatory to ensure that high biological value proteins are included in enteral formulae. To assess the biological quality of a protein blend constituted by 50% potassium caseinate, 25% whey protein and 25% pea protein intended to be used in enteral nutrition products. Forty Wistar rats (20 male and 20 female), with initial body weight of 51 g, where divided into four groups and feed for 10 days with: casein (Control), experimental protein blend (Experimental), liophylized normo- and hyperproteic enteral nutrition formulae adapted to the animal nutritional requirements (Normoproteic and Hyperproteic). Protein efficiency ratio (PER), apparent digestibility coefficient (ADC), relationship between retained and absorbed nitrogen (R/A) and relationship between retained and consumed nitrogen (R/I) where calculated. Experimental and control groups had similar values for all analysed indices (PER, ADC, R/A and R/I). These indices where also similar between normo and hyperproteic groups, but lower than experimental and control groups, except in PER, where normoproteic group was either similar to control and hiperproteic group. The quality of the protein blend used in this study is high. It is a good protein source to be used in the development of new enteral nutritional products.

  9. Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions

    Amachawadi, Raghavendra G.; Renter, David G.; Volkova, Victoriya V.

    2016-01-01

    Antimicrobial treatments result in the host’s enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-Test® following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: β-lactams (specifically, ampicillin and ceftriaxone E-Test®), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n≥30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment

  10. Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

    Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

    2003-08-01

    Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

  11. Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis

    Cheng, Ying; Zhang, Junfeng; Zhang, Liwei; Wu, Juan; Zhan, Zhen

    2018-01-01

    Background Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on bioch...

  12. Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

    Yongjian Wu

    2018-02-01

    Full Text Available Beta-defensins 2 and 3 (BD2 and BD3 are inducible peptides present at the sites of infection, and they are well characterized for their antimicrobial activities and immune-regulatory functions. However, no study has thoroughly investigated their immunomodulatory effects on macrophage-mediated immune responses against Pseudomonas aeruginosa (PA. Here, we use THP-1 and RAW264.7 cell lines and demonstrate that BD2 and BD3 suppressed macrophage autophagy but enhanced the engulfment of PA and Zymosan bioparticles as well as the formation of phagolysosomes, using immunofluorescence staining and confocal microscopy. Plate count assay showed that macrophage-mediated phagocytosis and intracellular killing of PA were promoted by BD2 and BD3. Furthermore, microarray and real-time PCR showed that the expression of two genes, early growth response gene-1 (EGR1 and c-FOS, was attenuated by BD2 and BD3. Western blot revealed that BD2 and BD3 inhibited the expression and nuclear translocation of EGR1 and c-FOS. Knockdown of EGR1 and c-FOS by siRNA transfection suppressed macrophage autophagy before and after PA infection; while overexpression of these two transcription factors enhanced autophagy but reversed the role of BD2 and BD3 on macrophage-mediated PA eradication. Together, these results demonstrate a novel immune defense activity of BD2 and BD3, which promotes clearance of PA by inhibiting macrophage autophagy through downregulation of EGR1 and c-FOS.

  13. Role of FODMAP content in enteral nutrition-associated diarrhea.

    Halmos, Emma P

    2013-12-01

    Gastrointestinal symptoms including diarrhea are common complications of enteral nutrition (EN); however, the cause is unclear. Mode of EN delivery that alters digestion and possibly absorption is suggested to contribute to the high incidence of diarrhea; however, enteral formula is frequently blamed. Most research has focused on fiber-supplemented EN, with a meta-analysis showing that fiber reduces the incidence of diarrhea in non-intensive care unit studies. Other hypotheses include formula osmolality and FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) content. FODMAPs are poorly absorbed short-chain carbohydrates that exert an osmotic effect. Dietary FODMAPs have been shown to reduce gastrointestinal symptoms, including diarrhea, in those with irritable bowel syndrome and, given a high-enough dose, will induce a laxative effect in most people. As FODMAPs are commonly added to enteral formula and EN is frequently used as the main source of nutrition, it is reasonable to hypothesize that EN provides more FODMAPs than usual dietary intake and increases risk for developing diarrhea. This hypothesis was assessed through a retrospective study showing that the standard-use enteral formula Isosource 1.5 had a protective effect of developing diarrhea. The only characteristic unique to Isosource 1.5 was the lower FODMAP content as determined through methodologies previously validated for food analysis. Methodologies for application to enteral formulas are currently undergoing formal validation. Once confirmed for application in enteral formula, future directions include FODMAP analysis of specific ingredients to increase understanding of potential problems associated with enteral formula and a randomized, controlled trial investigating the role of formula FODMAP content. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  14. Serotyping of Campylobacter jejuni from an outbreak of enteritis implicating chicken.

    Rosenfield, J A; Arnold, G J; Davey, G R; Archer, R S; Woods, W H

    1985-09-01

    An outbreak of campylobacter enteritis involving 7 of 17 people over a period of 5 days followed a dinner at a restaurant. A chicken casserole dish was implicated with a food-specific attack rate of 58%. Campylobacter jejuni Penner serotype 18/21/29, resistant to metronidazole, was isolated from 3 of 4 symptomatic patients and from three raw fresh chicken samples closely associated with the implicated chicken. Numbers of C. jejuni in the chicken ranged from 5.3 X 10(1) to 7.5 X 10(2) colony forming units per square centimeter of surface area. This is the first outbreak of campylobacter enteritis reported in Australia in which C. jejuni has been isolated from both human and food sources and the isolates serologically confirmed as identical.

  15. Enabling Passive Immunization as an Alternative to Antibiotics for Controlling Enteric Infections in Production Animals

    Heegaard, Peter M. H.; Hald, Birthe; Madsen, M.

    Enteric infections cause major problems in most intensive animal production sectors, including poultry, pigs and cattle, leading to disease, reduced production and compromised welfare. In addition some of these infections are zoonotic, and they are to a large extent responsible for the continued ...... as a viable strategy for control of infectious diseases in the intensive animal production, with the potential to significantly reduce antibiotics consumption.......Enteric infections cause major problems in most intensive animal production sectors, including poultry, pigs and cattle, leading to disease, reduced production and compromised welfare. In addition some of these infections are zoonotic, and they are to a large extent responsible for the continued...... massive use of antibiotics in food animals. Thus there is a pressing need for economically feasible, efficient, non-antibiotics based means for controlling the problem. Passive immunization has been known for decades as an efficient way of endowing humans or animals with short-term (weeks) immunity...

  16. Enviromental sanitation in urban and rural areas: its importance in the control of enteric infections.

    Wolman, A

    1975-01-01

    In Central and South America, enteric infections constitute one of the leading causes of disease and death. The terrible toll is exacted by a host of different microorganisms, virtually all of which are transmitted via contact with human excreta. To change this picture we need many more water supply and sewerage systems, better food preparation and handling, and public comprehension of how elementary good hygiene promotes good health. Attaining these objectives will be difficult, but less costly than one might suppose, and there is little to be gained by delay. The basic enviromental causes of enteric disease are clear, current conditions have been aggravated by rapid population growth and urbanization, and basic corrective measures have already been postponed long enough.

  17. Human waste

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  18. 42 CFR 137.285 - Are Self-Governance Tribes required to accept Federal environmental responsibilities to enter...

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Are Self-Governance Tribes required to accept..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Nepa Process § 137.285 Are Self-Governance Tribes required to accept Federal environmental responsibilities to enter into a construction...

  19. Zoonotic enteric parasites transmitted from dogs in Egypt with special concern to Toxocara canis infection

    Awadallah, Maysa A. I.; Salem, Lobna M. A.

    2015-01-01

    Aim: This work aimed to study the role played by dogs in transmitting zoonotic enteric parasites to humans in Egypt and to analyze the risk factors associated with the occurrence of such infection in dogs. Serodiagnosis of anti-Toxocara immunoglobulin G (IgG) antibodies among human beings as well as analyzing risk factors predispose to Toxocara canis infection in human beings are another objectives of this study. Materials and Methods: From June to December 2013, a total of 130 fecal samples from 4 dog populations (Military, nomadic and domiciled dogs from rural and high standard districts) and 150 stool samples of 6 occupational groups were examined for the presence of enteric parasitic infection. Moreover, 150 serum samples were collected from humans from whom stool samples were collected and examined for the presence of anti-T. canis antibodies. Results: Enteric parasites were detected in 30% of fecal samples from 4 dog populations in Egypt. High infectivity had been reported in nomadic dogs (63.33%) (Crude odds ratios [COR]=67.36, 95% confidence interval [CI]=8.09-560.8, p0.05) did not seem to have a significant association among the examined dogs. Enteric parasitic infection was reported in 31/150 human stools (20.67%). Students were the most affected groups (37.14%), followed by nomadic people (24%), house wives (20%), house guarders and military workers (12%, each), and employees (10%). The identified parasites were Cryptosporidium spp. (9.33%), Ascaris lumbercoides (3.33%), Heterophyes spp. and Ancylostoma spp. (2.66%, each) and Paragonimus spp. and Hymenolepis nana (1.33%, each). Toxocara IgG antibodies were detected in 36/150 (24%) serum samples investigated. Toxocara IgG antibodies were more prevalent in males (26.66%) than females (20%). Seroprevalence was highest (17/35, 48.57%) in 7-15 years old (COR=6.93, 95% CI=1.75-27.43, p=0.006). Seroprevalence values for T. canis antibodies were higher in those; raising dogs (29.85%), eating raw vegetables (25

  20. Human Rights in the Humanities

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  1. A dual mechanism involved in membrane and nucleic acid disruption of AvBD103b, a new avian defensin from the king penguin, against Salmonella enteritidis CVCC3377.

    Teng, Da; Wang, Xiumin; Xi, Di; Mao, Ruoyu; Zhang, Yong; Guan, Qingfeng; Zhang, Jun; Wang, Jianhua

    2014-10-01

    The food-borne bacterial gastrointestinal infection is a serious public health threat. Defensins are evolutionarily conserved innate immune components with broad-spectrum antibacterial activity that do not easily induce resistance. AvBD103b, an avian defensin with potent activity against Salmonella enteritidis, was isolated from the stomach contents of the king penguin (Aptenodytes patagonicus). To elucidate further the antibacterial mechanism of AvBD103b, its effect on the S. enteritidis CVCC3377 cell membrane and intracellular DNA was researched. The cell surface hydrophobicity and a N-phenyl-1-naphthylamine uptake assay demonstrated that AvBD103b treatment increased the cell surface hydrophobicity and outer membrane permeability. Atomic absorption spectrometry, ultraviolet spectrophotometry, flow cytometry, and transmission electron microscopy (TEM) indicated that AvBD103b treatment can lead to the release of the cellular contents and cell death through damage of the membrane. DNA gel retardation and circular dichroism analysis demonstrated that AvBD103b interacted with DNA and intercalated into the DNA base pairs. A cell cycle assay demonstrated that AvBD103b affected cellular functions, such as DNA synthesis. Our results confirmed that AvBD103b exerts its antibacterial activity by damaging the cell membrane and interfering with intracellular DNA, ultimately causing cell death, and suggested that AvBD103b may be a promising candidate as an alternative to antibiotics against S. enteritidis.

  2. [Enteral distress syndrome in surgery: definition, pathogenesis, diagnosis].

    Vlasov, A P; Trofimov, V A; Grigorieva, T I; Shibitov, V A; Vlasov, P A

    2016-01-01

    It was performed a comprehensive experimental and clinical study of functional and metabolic status of the intestine in acute peritonitis, pancreatic necrosis, acute intestinal obstruction. We obtained objective data of impaired barrier function based on levels of toxins in arterial and mesenteric venous blood. Association of organ and organismic homeostatic changes was revealed. It was proved an important role of membrane-destabilizing processes in intestinal epithelium as a cause of enteral insufficiency. Leading trigger mechanisms of lipid metabolic disorders were determined. Enteral distress syndrome was determined as pathological response to acute abdominal surgical diseases. Enteral distress syndrome is a complex of pathological processes due to membrane-destabilizing mechanisms, impaired intestinal barrier function followed by progression of endogenous intoxication. This syndrome significantly aggravates the course of acute surgical abdominal diseases.

  3. Implementation of enteral feeding protocol in an intensive care unit

    Padar, Martin; Uusvel, Gerli; Starkopf, Liis

    2017-01-01

    AIM: To determine the effects of implementing an enteral feeding protocol on the nutritional delivery and outcomes of intensive care patients. METHODS: An uncontrolled, observational before-and-after study was performed in a tertiary mixed medical-surgical intensive care unit (ICU). In 2013......, a nurse-driven enteral feeding protocol was developed and implemented in the ICU. Nutrition and outcome-related data from patients who were treated in the study unit from 2011-2012 (the Before group) and 2014-2015 (the After group) were obtained from a local electronic database, the national Population...... the groups. Patients in the After group had a lower 90-d (P = 0.026) and 120-d (P = 0.033) mortality. In the After group, enteral nutrition was prescribed less frequently (P = 0.039) on day 1 but significantly more frequently on all days from day 3. Implementation of the feeding protocol resulted in a higher...

  4. Enteral Nutrition Support to Treat Malnutrition in Inflammatory Bowel Disease

    Altomare, Roberta; Damiano, Giuseppe; Abruzzo, Alida; Palumbo, Vincenzo Davide; Tomasello, Giovanni; Buscemi, Salvatore; Lo Monte, Attilio Ignazio

    2015-01-01

    Malnutrition is a common consequence of inflammatory bowel disease (IBD). Diet has an important role in the management of IBD, as it prevents and corrects malnutrition. It is well known that diet may be implicated in the aetiology of IBD and that it plays a central role in the pathogenesis of gastrointestinal-tract disease. Often oral nutrition alone is not sufficient in the management of IBD patients, especially in children or the elderly, and must be combined with oral supplementation or replaced with tube enteral nutrition. In this review, we describe several different approaches to enteral nutrition—total parenteral, oral supplementation and enteral tube feeding—in terms of results, patients compliance, risks and and benefits. We also focus on the home entaral nutrition strategy as the future goal for treating IBD while focusing on patient wellness. PMID:25816159

  5. Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy

    Umpierrez, Guillermo E.

    2013-01-01

    Hyperglycemia is a frequent complication of enteral and parenteral nutrition in hospitalized patients. Extensive evidence from observational studies indicates that the development of hyperglycemia during parenteral and enteral nutrition is associated with an increased risk of death and infectious complications. There are no specific guidelines recommending glycemic targets and effective strategies for the management of hyperglycemia during specialized nutritional support. Managing hyperglycemia in these patients should include optimization of carbohydrate content and administration of intravenous or subcutaneous insulin therapy. The administration of continuous insulin infusion and insulin addition to nutrition bag are efficient approaches to control hyperglycemia during parenteral nutrition. Subcutaneous administration of long-acting insulin with scheduled or corrective doses of short-acting insulin is superior to the sliding scale insulin strategy in patients receiving enteral feedings. Randomized controlled studies are needed to evaluate safe and effective therapeutic strategies for the management of hyperglycemia in patients receiving nutritional support. PMID:23065369

  6. Genomic diversification of giant enteric symbionts reflects host dietary lifestyles

    Ngugi, David

    2017-08-24

    Herbivorous surgeonfishes are an ecologically successful group of reef fish that rely on marine algae as their principal food source. Here, we elucidated the significance of giant enteric symbionts colonizing these fishes regarding their roles in the digestive processes of hosts feeding predominantly on polysiphonous red algae and brown Turbinaria algae, which contain different polysaccharide constituents. Using metagenomics, single-cell genomics, and metatranscriptomic analyses, we provide evidence of metabolic diversification of enteric microbiota involved in the degradation of algal biomass in these fishes. The enteric microbiota is also phylogenetically and functionally simple relative to the complex lignocellulose-degrading microbiota of terrestrial herbivores. Over 90% of the enzymes for deconstructing algal polysaccharides emanate from members of a single bacterial lineage,

  7. Enteric Diseases of Poultry with Special Attention to Clostridium perfringens

    Hafez Mohamed Hafez

    2011-06-01

    Full Text Available The enteric heath of growing poultry is imperative to success of the production. The basic role of poultry production is turning feed stuffs into meat. Any changes in this turning process, due to mechanical, chemical or biological disturbance of digestive system (enteric disorders is mostly accompanied with high economic losses due to poor performance, increased mortality rates and increased medication costs. The severity of clinical signs and course of the disorders are influenced several factors such as management, nutrition and the involved agent(s. Several pathogens (viruses, bacteria and parasites are incriminated as possible cause of enteric disorders either alone (mono-causal, in synergy with other micro-organisms (multi-causal, or with non-infectious causes such as feed and /or management related factors. In addition, excessive levels of mycotoxins and biogenic amines in feed lead to enteric disorders. Also factors such as high stocking density, poor litter conditions, poor hygiene and high ammonia level and other stressful situation may reduce the resistance of the birds and increases their susceptibility to infections. Under field conditions, however, under filed conditions it is difficult to determine whether the true cause of enteric disorders, is of infectious or non-infectious origin. In recent years and since the ban of use of antimicrobial growth promoters in several countries the incidence of intestinal disorders especially those caused by clostridial infection was drastically increased. The present review described in general the several factors involved in enteric disorders and summarized the available literatures about Clostridium perfringens infection in poultry.

  8. Home parenteral nutrition in treatment of severe radiation enteritis

    Miller, D.G.; Ivey, M.; Young, J.

    1979-01-01

    Ten patients with radiation enteritis unresponsive to conventional medical and surgical therapy were put on long-term parenteral nutrition at home. Six of the patients are alive at home; four patients died, two from recurrent cancer. Some of the patients have been able to resume oral intake, but none have been able to discontinue parenteral nutrition. Fistulas healed or had a marked decrease in output. Two patients in our series were given prednisone and sulfasalazine without significant benefit, in contrast to previously reported clinical improvement of radiation enteritis with this therapy

  9. New Insights into c-Ret Signalling Pathway in the Enteric Nervous System and Its Relationship with ALS

    M. J. Luesma

    2014-01-01

    Full Text Available The receptor tyrosine kinase Ret (c-Ret transduces the glial cell line-derived neurotrophic factor (GDNF signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS. The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.

  10. New insights into c-Ret signalling pathway in the enteric nervous system and its relationship with ALS.

    Luesma, M J; Cantarero, I; Álvarez-Dotu, J M; Santander, S; Junquera, C

    2014-01-01

    The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS) during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS) study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.

  11. Review: Epidemiological evidence of groundwater contribution to global enteric disease, 1948-2015

    Murphy, Heather M.; Prioleau, Morgan D.; Borchardt, Mark A.; Hynds, Paul D.

    2017-06-01

    Globally, approximately 2.2 billion people rely on groundwater for daily consumption. It is widely accepted that groundwater is more pristine than surface water but while this assumption is frequently the case, groundwater is not ubiquitously free of contaminants; accordingly, this presumption can result in an unfounded and potentially hazardous sense of security among owners, operators and users. The current paper presents a review of published literature providing epidemiological evidence of the contribution of groundwater to global human enteric infection. An emphasis is placed on enteric pathogens transmitted via the faecal-oral route, and specifically those associated with acute gastrointestinal illness (AGI). The review identified 649 published groundwater outbreaks globally between 1948 and 2013 and several epidemiological studies that show there is an increased risk of AGI associated with the consumption of untreated groundwater. The review identified that the following five pathogens were responsible for most outbreaks: norovirus, Campylobacter, Shigella, Hepatitis A and Giardia. Crudely, the authors estimate that between 35.2 and 59.4 million cases of AGI per year globally could be attributable to the consumption of groundwater. Although groundwater is frequently presumed to be a microbiologically safe source of water for consumption, this review demonstrates that consumers served by an untreated groundwater supply remain at risk to enteric disease. The authors conclude that collaboration between microbiologists, hydrogeologists and epidemiologists is needed to better understand pathogen occurrence, persistence, detection and transport in groundwater as well as build stronger epidemiological evidence documenting the true magnitude of disease associated with groundwater globally.

  12. Concentration of enteric virus indicator from seawater using granular activated carbon.

    Cormier, Jiemin; Gutierrez, Miguel; Goodridge, Lawrence; Janes, Marlene

    2014-02-01

    Fecal contamination of shellfish growing seawater with enteric viruses is often associated with human outbreaks of gastroenteritis. Male specific bacteriophage MS2 is correlated with those of enteric viruses in a wide range of water environments and has been used widely as a surrogate for pathogenic waterborne viruses. Since viruses in contaminated water are usually at low levels, the development of methods to concentrate viruses from water is crucial for detection purposes. In the present study, granular activated carbon was evaluated for concentration of MS2 from artificial seawater, and different parameters of the seawater were also compared. Recovery of MS2 from warm seawater (37°C) was found to be significantly greater than from cold seawater (4 and 20°C), and even greater than from fresh water (4, 20 and 37°C); the difference between seawater and fresh water became less profound when the temperatures of both were below 37°C. Although not of statistical significance, recovery of MS2 from low salinity seawater (10 and 20 parts per thousand, ppt) was greater than from high salinity seawater (30 and 40ppt). One gram of granular activated carbon was able to extract 6-log plaque forming units (PFU) of MS2 from 500ml seawater at 37°C. This study demonstrated that granular activated carbon can concentrate an enteric virus indicator from shellfish growing seawater effectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Epidemiology and geographical distribution of enteric protozoan infections in Sydney, Australia

    Stephanie Fletcher

    2014-07-01

    Full Text Available Background. Enteric protozoa are associated with diarrhoeal illnesses in humans; however there are no recent studies on their epidemiology and geographical distribution in Australia. This study describes the epidemiology of enteric protozoa in the state of New South Wales and incorporates spatial analysis to describe their distribution. Design and methods. Laboratory and clinical records from four public hospitals in Sydney for 910 patients, who tested positive for enteric protozoa over the period January 2007-December 2010, were identified, examined and analysed. We selected 580 cases which had residence post code data available, enabling us to examine the geographic distribution of patients, and reviewed the clinical data of 252 patients to examine possible links between protozoa, demographic and clinical features. Results. Frequently detected protozoa were Blastocystis spp. (57%, Giardia intestinalis (27% and Dientamoeba fragilis (12%. The age distribution showed that the prevalence of protozoa decreased with age up to 24 years but increasing with age from 25 years onwards. The geographic provenance of the patients indicates that the majority of cases of Blastocystis (53.1% are clustered in and around the Sydney City Business District, while pockets of giardiasis were identified in regional/rural areas. The distribution of cases suggests higher risk of protozoan infection may exist for some communities. Conclusions. These findings provide useful information for policy makers to design and tailor interventions to target high risk communities. Follow-up investigation into the risk factors for giardiasis in regional/rural area is needed.

  14. Comparison of the EntericBio multiplex PCR system with routine culture for detection of bacterial enteric pathogens.

    O'Leary, James

    2009-11-01

    The EntericBio system uses a multiplex PCR assay for the simultaneous detection of Campylobacter spp., Salmonella enterica, Shigella spp., and Escherichia coli O157 from feces. It combines overnight broth enrichment with PCR amplification and detection by hybridization. An evaluation of this system was conducted by comparing the results obtained with the system with those obtained by routine culture, supplemented with alternative PCR detection methods. In a study of 773 samples, routine culture and the EntericBio system yielded 94.6 and 92.4% negative results, respectively. Forty-two samples had positive results by culture, and all of these were positive with the EntericBio system. This system detected an additional 17 positive samples (Campylobacter spp., n = 12; Shigella spp., n = 1; E. coli O157, n = 4), but the results for 5 samples (Campylobacter spp., n = 2; Shigella spp., n = 1; E. coli O157, n = 2) could not be confirmed. The target for Shigella spp. detected by the EntericBio system is the ipaH gene, and the molecular indication of the presence of Shigella spp. was investigated by sequence analysis, which confirmed that the ipaH gene was present in a Klebsiella pneumoniae isolate from the patient. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 99.3%, 91.5%, and 100%, respectively. Turnaround times were significantly reduced with the EntericBio system, and a result was available between 24 and 32 h after receipt of the sample in the laboratory. In addition, the amount of laboratory waste was significantly reduced by use of this system. In summary, the EntericBio system proved convenient to use, more sensitive than the conventional culture used in this study, and highly specific; and it generated results significantly faster than routine culture for the pathogens tested.

  15. Formation and malformation of the enteric nervous system

    J.H.C. Meijers (Johan)

    1989-01-01

    textabstractTo clarify pathogenetic mechanisms of congenital malformations of the ENS, the formation of the ENS was investigated in chicken and murine embryos. The experimental work was concentrated on several aspects of the interaction between neural crest cells and the enteric microenvironment.

  16. Natural history and surgical management of radiation enteritis

    Galland, R.B.; Spencer, J.

    1987-01-01

    The natural history and surgical management of radio enteritis is reviewed. Predisposing factors include the dose of radiation patients build, combination with chemotherapy, previous operations and vascular disease. Management is related to the stage of disease at presentation, and tailored to the clinical problem. Surgical management must take into account the poor healing associated with irradiated intestine. (author)

  17. Case Study: Enteral formula: Selecting the right formula for your ...

    placed on the type of fat (mono-unsaturated fatty acids), the addition ... patient with normal GIT function, but could worsen symptoms of poor enteral feed tolerance in a .... of omega-3 fatty acids, as well as gamma-linolenic acid (GLA) reflect an ...

  18. Overconfidence of Vocational Education Students When Entering Higher Education

    Bowden, Mark P.; Abhayawansa, Subhash; Bahtsevanoglou, John

    2015-01-01

    Purpose: There is evidence that students who attend Technical and Further Education (TAFE) prior to entering higher education underperform in their first year of study. The purpose of this paper is to examine the role of self-efficacy in understanding the performance of students who completed TAFE in the previous year in a first year subject of…

  19. Persistence of enteric viruses within oysters (Crassostrea virginica)

    It is well known that water-borne enteric viruses are concentrated by bivalves. Why these viruses are selectively retained and remain infectious within shellfish tissues for extended periods is unknown. Our current hypothesis is that phagocytic hemocytes (blood cells) are a site of virus persiste...

  20. Critical Success Factors for Franchised Restaurants Entering the Kenyan Market

    Lucy Gikonyo; Adele Berndt; Joseph Wadawi

    2015-01-01

    In today’s globalized world, businesses look to expand to have a global presence. Restaurant businesses have expanded internationally using franchising. This study sought to determine the critical success factors (CSFs) of a franchised restaurant system entering the Kenyan market from the franchisors’ perspective. It sought to establish how franchisors define, identify, and evaluate success. This study provides a theor...

  1. Defining travel-associated cases of enteric fever.

    Freedman, Joanne; Lighton, Lorraine; Jones, Jane

    2014-01-01

    There is no internationally recognized case-definition for travel-associated enteric fever in non-endemic countries. This study describes the patterns of case reporting between 2007 and 2011 as travel-associated or not from the surveillance data in England, Wales and Northern Ireland (EWNI), before and after a change in the time component of the case-definition in January 2011. It examines in particular the role of a time frame based on the reported typical incubation period in defining a case of travel-associated enteric fever. The results showed no significant differences in the distribution of cases of enteric fever in regards to the interval between the onset and UK arrival in 2011 compared to 2007-2010 (p=0.98 for typhoid and paratyphoid A); the distribution for paratyphoid B was also similar in both time periods. During 2007-2010, 93% (1730/1853) of all of the cases were classified as travel-associated compared to 94% (448/477) in 2011. This difference was not statistically significant. Changing the time component of the definition of travel-associated enteric fever did not make a significant difference to the proportion of travel-associated cases reported by investigators. Our analysis suggests that time might be subordinate to other considerations when investigators classify a case as travel-associated. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  2. [ENTERAL NUTRITION ON THE NUTRITIONAL STATUS OF CANCER].

    Escortell Sánchez, Raquel; Reig García-Galbis, Manuel

    2015-10-01

    to identify what effect causes enteral nutrition on nutritional status of cancer. a search was performed using the keywords "Cancer" AND "Enteral Nutrition" AND "Supplementation" in four document databases: Pubmed, EBSCO, ProQuest, and Web of Science. age of the sample, major than 18 years; submitted to surgery for cancer; that the intervention program was including diet and employment or not of nutritional Supplementation; clinical trials published between January 2004 and December 2014, in scientific journals indexed. we analyzed 660 articles, of which only 2% has been included. 58% of intervention programs are applied outside Spain; 84% of the interventions was carried out in a hospitable ambient; 58% of the sample is formed by adults older than 54 years; 33% of the interventions were multidisciplinary and its duration ranges between 1 and 4 years. we found just a few national interventions in cancer participants and there two types of interventions: by exclusive polymeric enteral formula or mixed with immunonutrition. enteral nutrition shows against the parenteral and its introduction at an early stage, it helps to improve nutritional status of the patient; polymeric formulas next immunonutrition, it helps to reduce the time of hospitalization; the analytical parameters are shown as a measurement pattern when assessing the improvement in nutritional status in cancer. It is recommended to increase the research in this field, especially in children. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  3. characterisation of gastro- enteritis-associated adenoviruses in ...

    Objective. To analyse adenovirus (Ad) numbers and types associated with paediatric gastro-enteritis in South Africa. Setting. Gauteng, 1994-1996. Metfwds. A total of 234 paediatric diarrhoeal stool samples were screened for Ad using commercial enzyme-linked. iInmunosorbent assays (EUSAs). Adenoviral isolates were.

  4. Can wheat bran mitigate malnutrition and enteric pathogens?

    Child malnutrition is a complex global problem, of which lack of food is only one component. Enteric pathogens and malnutrition work in a cyclic manner to depress a child’s intestinal immunity, while decreasing nutrient absorption. This cycle leads to stunting, wasting, and death. Often malnourished...

  5. Early enteral nutrition compared to outcome in critically ill trauma ...

    2014-11-01

    Nov 1, 2014 ... 16.4 days, p-value 0.00315) and mortality (9.5 % vs. 20.7 % ..... had a more complicated clinical picture, despite no significant differences in terms ... In other words, an early enteral nutrition start was associated with an almost.

  6. Barriers and strategies for innovations entering BoP markets

    Kamp, L.M.; Ortt, J.R.; Harahap, B.

    2015-01-01

    Companies that bring a new product to the market or enter a new market with an existing product, come across a number of barriers that prevent large?scale diffusion. In order to circumvent or remove these barriers, they can adopt alternative strategies. This paper looks into these barriers and

  7. Regional enteritis and gluten-free diet. A clinical study

    Merwe, Christiaan Frederik van der

    1974-01-01

    The purpose of this clinical study was to determine whether the use of a gluten-free diet influenced the course and prognosis of regional enteritis. Following a few clinical communications in the Dutch medical literature reporting favourable results obtained with the gluten-free diet in the

  8. Plasticity and Neural Stem Cells in the Enteric Nervous System

    Schaefer, Karl-Herbert; Van Ginneken, Chris; Copray, Sjef

    2009-01-01

    The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to

  9. Single-layer closure of typhoid enteric perforation: Our experience ...

    Materials and Methods: We retrospectively studied the effects of single versus double layer intestinal closure after typhoid enteric perforation with peritonitis in 902 pediatric patients from September 2007 to April 2012. All the patients underwent laparotomy after resuscitation and antibiotic cover. The patients were divided ...

  10. Antibiotic-Resistant Enteric Bacteria in Environmental Waters

    Lisa M. Casanova; Mark D. Sobsey

    2016-01-01

    Sources of antibiotic resistant organisms, including concentrated animal feeding operations (CAFOs), may lead to environmental surface and groundwater contamination with resistant enteric bacteria of public health concern. The objective of this research is to determine whether Salmonella, Escherichia coli, Yersinia enterocolitica, and enterococci resistant to clinically relevant antibiotics are present in surface and groundwater sources in two eastern North Carolina counties, Craven and Wayne...

  11. 9 CFR 355.21 - Products entering inspected plants.

    2010-01-01

    ... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Products entering inspected plants. 355.21 Section 355.21 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF...

  12. Enteral feeding practices in preterm infants in South Africa

    Background. Optimal feeding regimens in babies weighing <1 000 g have not been established, and wide variations occur. In South Africa. (SA) this situation is complicated by varied resource constraints. Objective. To determine the preterm enteral feeding practices of paediatricians in SA. Methods. We invited 288 ...

  13. Risk Factors Associated With Canine Parvovirus Enteritis In Vom ...

    Risk Factors Associated With Canine Parvovirus Enteritis In Vom And Environs. J G Mohammed, AO Ogbe, NJ Zwandor, JU Umoh. Abstract. No Abstract. Animal Research International Vol. 2 (3) 2005 pp. 366-368. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  14. The Future Entering: Reflections on and Challenges to Ethical Leadership

    Reilly, Elizabeth C.

    2006-01-01

    To enter a future that waits to be born, educational leaders must continually assess their own ethical stance as well as that of the organizations they serve. Three frames form a model for examining the ethics of both individual and organization, with internal monologue and engaged conversation as the means for reflection and action.

  15. Glutamine-enriched enteral diet increases renal arginine production

    Houdijk, A. P.; van Leeuwen, P. A.; Teerlink, T.; FLINKERBUSCH, E. L.; Boermeester, M. A.; Sauerwein, H. P.; Wesdorp, R. I.

    1994-01-01

    Arginine (Arg) is generated in the kidney by the conversion of circulating citrulline. The most important source for circulating citrulline is the metabolism of glutamine (Gln) by the gut. In this study, we investigated the influence of an enteral diet enriched with Gln on renal Arg synthesis in the

  16. Eosinophilic enteritis – A diagnostic dilemma | Clegg-Lamptey ...

    It may mimic peptic ulcer, subacute (or chronic) intestinal obstruction, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease. The diagnosis is often ... Finalement laparotomy a revele des segments enflames de petit intestin, une biopsie de qui a montré Eosinophilic enteritis. Le malade a été traite par la ...

  17. Differential Effects of Statins on Inflammatory Interleukin-8 and Antimicrobial Peptide Human Β-Defensin 2 Responses in Salmonella-Infected Intestinal Epithelial Cells

    Fu-Chen Huang

    2018-06-01

    Full Text Available Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis. Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella-infected intestinal epithelial cells (IECs, which are involved in mucosal innate immunity. SW480 cells and Akt siRNA- or vitamin D receptor (VDR siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins. The mRNA or protein expression was analyzed by real-time quantitative PCR or western blot analysis, respectively. Simvastatin or fluvastatin caused IL-8 (interleukin-8 suppression, but increased hBD-2 mRNA expression in Salmonella-infected SW480 cells. Both statins enhanced phosphorylated Akt and VDR expressions. Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Therefore, we observed differential regulation of statins on inflammatory IL-8 and anti-microbial hBD-2 expressions in Salmonella-infected IECs via PI3K/Akt signaling and VDR protein expression, respectively. The enhanced activity of antimicrobial peptides by statins in Salmonella-infected IECs could protect the host against infection, and modulation of pro-inflammatory responses could prevent the detrimental effects of overwhelming inflammation in the host.

  18. Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat.

    Knodell, R G; Spector, M H; Brooks, D A; Keller, F X; Kyner, W T

    1980-12-01

    Recent in vitro observations suggest that the intestine, in addition to the liver, may be an important organ of first-pass drug metabolism. While a variety of changes in intestinal morphology and function in response to continuous parenteral and enteral nutrition have been documented, the effect of different routes of alimentation on intestinal drug metabolism has not been previously investigated. Objectives of this study were to assess the contribution of intestinal pentobarbital metabolism to overall in vivo pentobarbital pharmacokinetics in the rat and to determine if differences in pentobarbital pharmacokinetics were seen between parenterally and enterally nourished animals. After 7 days of continuous infusion of amino acid-glucose mixture via a gastric or jugular vein catheter, pharmacokinetic parameters were determined after 40 mg/kg of pentobarbital was given orally or into the portal or femoral vein. Reduced systemic availability of pentobarbital after oral administration as compared to portal vein injection was seen in both alimentation groups indicating that significant intestinal metabolism of pentobarbital occurred in vivo. Total area under the pentobarbital plasma concentration-time curve was significantly greater in parenterally nourished animals as compared with enterally alimented animals after oral, portal vein and systemic vein drug administration. Differences in pentobarbital, pharmacokinetics between the two alimentation groups appeared to be primarly due to effects on hepatic pentobarbital metabolism. While the mechanism producing these changes has not been defined, differences in gut hormones release and/or pancreatic secretion in response to the two routes of alimentation may be contributory. The widespread use of enteral and parenteral alimentation in clinical medicine suggests that studies to determine if nutrition route of administration similarly influences drug metabolism in humans may be indicated.

  19. In Vitro Evaluation of Eslicarbazepine Delivery via Enteral Feeding Tubes.

    Reindel, Kristin; Zhao, Fang; Hughes, Susan; Dave, Vivek S

    2017-12-01

    Purpose: The feasibility of preparing an eslicarbazepine acetate suspension using Aptiom tablets for administration via enteral feeding tubes was evaluated. Methods: Eslicarbazepine acetate suspension (40 mg/mL) was prepared using Aptiom tablets after optimizing the tablet crushing methods and the vehicle composition. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to monitor the eslicarbazepine stability in the prepared suspension. Three enteric feeding tubes of various composition and dimensions were evaluated for the delivery of the suspensions. The suspension was evaluated for the physical and chemical stability for 48 hours. Results: The reproducibility and consistency of particle size reduction was found to be best with standard mortar/pestle. The viscosity analysis and physical stability studies showed that ORA-Plus:water (50:50 v/v) was optimal for suspending ability and flowability of suspension through the tubes. The developed HPLC method was found to be stability indicating and suitable for the assay of eslicarbazepine acetate in the prepared suspension. The eslicarbazepine concentrations in separately prepared suspensions were within acceptable range (±3%), indicating accuracy and reproducibility of the procedure. The eslicarbazepine concentrations in suspensions before and after delivery through the enteric feeding tubes were within acceptable range (±4%), indicating absence of any physical/chemical interactions of eslicarbazepine with the tubes and a successful delivery of eslicarbazepine dosage via enteric feeding tubes. The stability study results showed that eslicarbazepine concentration in the suspension remained unchanged when stored at room temperature for 48 hours. Conclusion: The study presents a convenient procedure for the preparation of a stable suspension of eslicarbazepine acetate (40 mg/mL) using Aptiom tablets, for administration via enteral feeding tubes.

  20. IODINE CONTENT OF ENTERAL AND PARENTERAL NUTRITION SOLUTIONS.

    Willard, Devina L; Young, Lorraine S; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N

    2017-07-01

    Iodine is essential for thyroid hormone synthesis, and iodine deficiency may result in thyroid disorders including goiter and hypothyroidism. Patients on long-term enteral nutrition (EN) or parenteral nutrition (PN) may be at risk for micronutrient deficiencies. The recommended daily allowance for iodine intake is 150 μg for nonpregnant adults. However, there is no current consensus among scientific societies regarding the quantity of iodine to be added in adult EN and PN formulations. The objective of this study was to determine the iodine content of U.S. adult enteral and parenteral nutrition solutions. This study also aimed to determine whether adult patients in the United States who are receiving long-term artificial nutrition may be at risk for iodine deficiency. Ten enteral nutrition solutions and 4 parenteral nutrition solutions were evaluated. The iodine contents of these solutions were measured spectrophotometrically and compared to the labeled contents. Measured and labeled EN iodine contents were similar (range 131-176 μg/L and 106-160 μg/L, respectively). In contrast, PN formulas were found to contain small, unlabeled amounts of iodine, averaging 27 μg/L. Typical fluid requirements are 30 to 40 mL/kg/day for adults receiving either total EN (TEN) or total PN (TPN). Adults on long-term TEN likely consume enough servings to meet their daily iodine requirements. However, patients on long-term TPN would require on average 5.6 L PN/day to meet the recommended daily allowance of iodine. This volume of PN is far in excess of typical consumption. Thus, U.S. patients requiring long-term TPN may be at risk for iodine deficiency. EN = enteral nutrition; PN = parenteral nutrition; TEN = total enteral nutrition; TPN = total parenteral nutrition; UIC = urinary iodine concentration.

  1. Defensin-like ZmES4 mediates pollen tube burst in maize via opening of the potassium channel KZM1.

    Suseno Amien

    2010-06-01

    Full Text Available In contrast to animals and lower plant species, sperm cells of flowering plants are non-motile and are transported to the female gametes via the pollen tube, i.e. the male gametophyte. Upon arrival at the female gametophyte two sperm cells are discharged into the receptive synergid cell to execute double fertilization. The first players involved in inter-gametophyte signaling to attract pollen tubes and to arrest their growth have been recently identified. In contrast the physiological mechanisms leading to pollen tube burst and thus sperm discharge remained elusive. Here, we describe the role of polymorphic defensin-like cysteine-rich proteins ZmES1-4 (Zea mays embryo sac from maize, leading to pollen tube growth arrest, burst, and explosive sperm release. ZmES1-4 genes are exclusively expressed in the cells of the female gametophyte. ZmES4-GFP fusion proteins accumulate in vesicles at the secretory zone of mature synergid cells and are released during the fertilization process. Using RNAi knock-down and synthetic ZmES4 proteins, we found that ZmES4 induces pollen tube burst in a species-preferential manner. Pollen tube plasma membrane depolarization, which occurs immediately after ZmES4 application, as well as channel blocker experiments point to a role of K(+-influx in the pollen tube rupture mechanism. Finally, we discovered the intrinsic rectifying K(+ channel KZM1 as a direct target of ZmES4. Following ZmES4 application, KZM1 opens at physiological membrane potentials and closes after wash-out. In conclusion, we suggest that vesicles containing ZmES4 are released from the synergid cells upon male-female gametophyte signaling. Subsequent interaction between ZmES4 and KZM1 results in channel opening and K(+ influx. We further suggest that K(+ influx leads to water uptake and culminates in osmotic tube burst. The species-preferential activity of polymorphic ZmES4 indicates that the mechanism described represents a pre-zygotic hybridization

  2. Defensin-Like ZmES4 Mediates Pollen Tube Burst in Maize via Opening of the Potassium Channel KZM1

    Márton, Mihaela L.; Debener, Thomas; Geiger, Dietmar; Becker, Dirk; Dresselhaus, Thomas

    2010-01-01

    In contrast to animals and lower plant species, sperm cells of flowering plants are non-motile and are transported to the female gametes via the pollen tube, i.e. the male gametophyte. Upon arrival at the female gametophyte two sperm cells are discharged into the receptive synergid cell to execute double fertilization. The first players involved in inter-gametophyte signaling to attract pollen tubes and to arrest their growth have been recently identified. In contrast the physiological mechanisms leading to pollen tube burst and thus sperm discharge remained elusive. Here, we describe the role of polymorphic defensin-like cysteine-rich proteins ZmES1-4 (Zea mays embryo sac) from maize, leading to pollen tube growth arrest, burst, and explosive sperm release. ZmES1-4 genes are exclusively expressed in the cells of the female gametophyte. ZmES4-GFP fusion proteins accumulate in vesicles at the secretory zone of mature synergid cells and are released during the fertilization process. Using RNAi knock-down and synthetic ZmES4 proteins, we found that ZmES4 induces pollen tube burst in a species-preferential manner. Pollen tube plasma membrane depolarization, which occurs immediately after ZmES4 application, as well as channel blocker experiments point to a role of K+-influx in the pollen tube rupture mechanism. Finally, we discovered the intrinsic rectifying K+ channel KZM1 as a direct target of ZmES4. Following ZmES4 application, KZM1 opens at physiological membrane potentials and closes after wash-out. In conclusion, we suggest that vesicles containing ZmES4 are released from the synergid cells upon male-female gametophyte signaling. Subsequent interaction between ZmES4 and KZM1 results in channel opening and K+ influx. We further suggest that K+ influx leads to water uptake and culminates in osmotic tube burst. The species-preferential activity of polymorphic ZmES4 indicates that the mechanism described represents a pre-zygotic hybridization barrier and may be a

  3. Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?

    Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Blandizzi, Corrado; Fornai, Matteo

    2018-05-24

    Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.

  4. Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

    Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

    2017-01-01

    Background Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty-seven studies met the inclusion

  5. Epidemiology of Enteric Disease in C-EnterNet’s Pilot Site – Waterloo Region, Ontario, 1990 to 2004

    Victoria A Keegan

    2009-01-01

    Full Text Available OBJECTIVE: The objective of the present study was to describe the epidemiology of reportable enteric illness in Ontario’s Waterloo region, including comparing calculated incidence rates with published rates, and adjusting for under-reporting to determine the number of community cases, where published data were available.

  6. DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients

    Ludovica Segat

    2014-11-01

    Full Text Available The human beta defensin 1 (hBD-1 antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV. In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5’UTR and c.*5G>A and c.*87A>G in the 3’UTR in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.

  7. Entering adulthood in a recession tempers later narcissism.

    Bianchi, Emily C

    2014-07-01

    Despite widespread interest in narcissism, relatively little is known about the conditions that encourage or dampen it. Drawing on research showing that macroenvironmental conditions in emerging adulthood can leave a lasting imprint on attitudes and behaviors, I argue that people who enter adulthood during recessions are less likely to be narcissistic later in life than those who come of age in more prosperous times. Using large samples of American adults, Studies 1 and 2 showed that people who entered adulthood during worse economic times endorsed fewer narcissistic items as older adults. Study 3 extended these findings to a behavioral manifestation of narcissism: the relative pay of CEOs. CEOs who came of age in worse economic times paid themselves less relative to other top executives in their firms. These findings suggest that macroenvironmental experiences at a critical life stage can have lasting implications for how unique, special, and deserving people believe themselves to be. © The Author(s) 2014.

  8. Multidrug resistance in enteric and other gram-negative bacteria.

    George, A M

    1996-05-15

    In Gram-negative bacteria, multidrug resistance is a term that is used to describe mechanisms of resistance by chromosomal genes that are activated by induction or mutation caused by the stress of exposure to antibiotics in natural and clinical environments. Unlike plasmid-borne resistance genes, there is no alteration or degradation of drugs or need for genetic transfer. Exposure to a single drug leads to cross-resistance to many other structurally and functionally unrelated drugs. The only mechanism identified for multidrug resistance in bacteria is drug efflux by membrane transporters, even though many of these transporters remain to be identified. The enteric bacteria exhibit mostly complex multidrug resistance systems which are often regulated by operons or regulons. The purpose of this review is to survey molecular mechanisms of multidrug resistance in enteric and other Gram-negative bacteria, and to speculate on the origins and natural physiological functions of the genes involved.

  9. Zoonotic enteric parasites transmitted from dogs in Egypt with special concern to Toxocara canis infection

    Maysa A. I. Awadallah

    2015-08-01

    Full Text Available Aim: This work aimed to study the role played by dogs in transmitting zoonotic enteric parasites to humans in Egypt and to analyze the risk factors associated with the occurrence of such infection in dogs. Serodiagnosis of anti-Toxocara immunoglobulin G (IgG antibodies among human beings as well as analyzing risk factors predispose to Toxocara canis infection in human beings are another objectives of this study. Materials and Methods: From June to December 2013, a total of 130 fecal samples from 4 dog populations (Military, nomadic and domiciled dogs from rural and high standard districts and 150 stool samples of 6 occupational groups were examined for the presence of enteric parasitic infection. Moreover, 150 serum samples were collected from humans from whom stool samples were collected and examined for the presence of anti-T. canis antibodies. Results: Enteric parasites were detected in 30% of fecal samples from 4 dog populations in Egypt. High infectivity had been reported in nomadic dogs (63.33% (Crude odds ratios [COR]=67.36, 95% confidence interval [CI]=8.09-560.8, p˂0.000, followed by domiciled dogs from rural areas (40% (COR=26, 95% CI=3.14-215.54, p=0.003, domiciled dogs from high standard areas (23.33% (COR=11.87, 95% CI=1.37-102.69, p=0.025 and military dogs (2.5%. Twelve species of enteric parasites were identified, Ancylostomatidae (6.15%, T. canis and Cryptosporidium spp. (5.38%, each, Heterophyes spp. (3.85%, Toxocara leonina and Blastocystis spp. (3.07%, Taenidae eggs (2.31%, Hymenolepis diminuta (1.54% and Entamoeba canis, Cyclospora cayetanensis, and Paragonimus spp. (0.77%, each. Univariate logestic regression revealed significant association of age (COR=4.73, 95% CI=2.13-10.53, p˂0.000, gender (COR=2.63, 95% CI=1.22-5.68, p˂0.014, housing system (COR=5.10, 95% CI=2.04-12.75, p˂0.000 with enteric parasitic infection in dogs. However, breeds (COR=6.91, 95% CI=0.88-54.52, p=0.067 and type of feeding (COR ranged from 3.5 to

  10. Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis

    Hille, A.; Christiansen, H.; Pradier, O.; Hermann, R.M.; Siekmeyer, B.; Weiss, E.; Hess, C.F.; Schmidberger, H.; Hilgers, R.

    2005-01-01

    Background and purpose: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. Patients and methods: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. Results: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). Conclusion: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration. (orig.)

  11. Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis

    Hille, A.; Christiansen, H.; Pradier, O.; Hermann, R.M.; Siekmeyer, B.; Weiss, E.; Hess, C.F.; Schmidberger, H. [Goettingen Univ. (Germany). Dept. of Radiotherapy and Radiation; Hilgers, R. [Goettingen Univ. (Germany). Dept. for Medical Statisics

    2005-09-15

    Background and purpose: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. Patients and methods: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. Results: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). Conclusion: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration. (orig.)

  12. Enteral Formula Containing Egg Yolk Lecithin Improves Diarrhea.

    Akashi, Tetsuro; Muto, Ayano; Takahashi, Yayoi; Nishiyama, Hiroshi

    2017-09-01

    Diarrhea often occurs during enteral nutrition. Recently, several reports showed that diarrhea improves by adding egg yolk lecithin, an emulsifier, in an enteral formula. Therefore, we evaluated if this combination could improve diarrhea outcomes. We retrospectively investigated the inhibitory effects on watery stools by replacing a polymeric fomula with that containing egg yolk lecithin. Then, we investigated the emulsion stability in vitro. Next, we examined the lipid absorption using different emulsifiers among bile duct-ligated rats and assessed whether egg yolk lecithin, medium-chain triglyceride, and dietary fiber can improve diarrhea outcomes in a rat model of short bowel syndrome. Stool consistency or frequency improved on the day after using the aforementioned combination in 13/14 patients. Average particle size of the egg yolk lecithin emulsifier did not change by adding artificial gastric juice, whereas that of soy lecithin and synthetic emulsifiers increased. Serum triglyceride concentrations were significantly higher in the egg yolk lecithin group compared with the soybean lecithin and synthetic emulsifier groups in bile duct-ligated rats. In rats with short bowels, the fecal consistency was a significant looser the dietary fiber (+) group than the egg yolk lecithin (+) groups from day 6 of test meal feedings. The fecal consistency was also a significant looser the egg yolk lecithin (-) group than the egg yolk lecithin (+) groups from day 4 of test meal feeding. The fecal consistency was no significant difference between the medium-chain triglycerides (-) and egg yolk lecithin (+) groups. Enteral formula emulsified with egg yolk lecithin promotes lipid absorption by preventing the destruction of emulsified substances by gastric acid. This enteral formula improved diarrhea and should reduce the burden on patients and healthcare workers.

  13. Enteral Nutrition for Feeding Severely Underfed Patients with Anorexia Nervosa

    Maria Gabriella Gentile

    2012-09-01

    Full Text Available Severe undernutrition nearly always leads to marked changes in body spaces (e.g., alterations of intra-extracellular water and in body masses and composition (e.g., overall and compartmental stores of phosphate, potassium, and magnesium. In patients with severe undernutrition it is almost always necessary to use oral nutrition support and/or artificial nutrition, besides ordinary food; enteral nutrition should be a preferred route of feeding if there is a functional accessible gastrointestinal tract. Refeeding of severely malnourished patients represents two very complex and conflicting tasks: (1 to avoid “refeeding syndrome” caused by a too fast correction of malnutrition; (2 to avoid “underfeeding” caused by a too cautious rate of refeeding. The aim of this paper is to discuss the modality of refeeding severely underfed patients and to present our experience with the use of enteral tube feeding for gradual correction of very severe undernutrition whilst avoiding refeeding syndrome, in 10 patients aged 22 ± 11.4 years and with mean initial body mass index (BMI of 11.2 ± 0.7 kg/m2. The mean BMI increased from 11.2 ± 0.7 kg/m2 to 17.3 ± 1.6 kg/m2 and the mean body weight from 27.9 ± 3.3 to 43.0 ± 5.7 kg after 90 days of intensive in-patient treatment (p < 0.0001. Caloric intake levels were established after measuring resting energy expenditure by indirect calorimetry, and nutritional support was performed with enteral feeding. Vitamins, phosphate, and potassium supplements were administered during refeeding. All patients achieved a significant modification of BMI; none developed refeeding syndrome. In conclusion, our findings show that, even in cases of extreme undernutrition, enteral feeding may be a well-tolerated way of feeding.

  14. When IKEA enters : Do local retailers win or lose?

    Daunfeldt, Sven-Olov; Mihaescu, Oana; Nilsson, Helena; Rudholm, Niklas

    2015-01-01

    IKEA is one of the world’s largest retailers, but little is known about how IKEA impact incumbent retailers when deciding to enter a local market. Previous studies on the effects of big-box entry on surrounding retailers have also generated inconclusive results, and mainly been focused towards entry of Wal-Mart in the United States. We contribute to this literature by investigating the effects of IKEA entry on revenues and employment for incumbent retail firms in three Swedish municipalities ...

  15. Haemorrhagic enteritis seroconversion in turkey breeders: field observations

    Raffaella Ceruti

    2010-01-01

    Full Text Available Seroconversion to viral haemorrhagic enteritis (HE was studied in seven flocks of turkey breeders (17.974 birds in total, after 20 weeks of the onset of egg production. They showed no clinical signs, and mortality rate was normal. However, the infection caused a drop in egg production lasting about five weeks (-2.32 eggs laid during this period, but had no effect on hatching parameters.

  16. The use of specialised enteral formulae for patients with diabetes ...

    The majority of enteral nutrition products for diabetes mellitus have a carbohydrate content of 30–45% and fat between 40–49%, mainly monounsaturated fat, with a mix of soluble and insoluble fibre (total of 14–24 g/l). Does this have short- and long-term benefits and which component(s) is/are crucial for the outcome or is it ...

  17. How EPC firms can enter the nuclear renaissance

    Locatelli, Giorgio; Mancini, Mauro

    2012-01-01

    the so called “nuclear renaissance” is creating a millionaire market for new nuclear reactors. Few firms have the capabilities to work in this complex and highly demanding market, whereas many other are investigating the option to enter. Quite surprising the international scientific literature provides information regarding the high-level governmental aspects of nuclear power programs in different countries while the analysis at firm level is almost inexistent. Moreover the usual business mod...

  18. Enticing consumers to enter fashion stores : a sensory marketing perspective

    Abazi, Jeton; Sohani, Armin

    2016-01-01

    During the past years, there has been a re-emergence of sensory marketing in the paradigm of marketing. However, there is a lack of empirical studies done on the subject. Furthermore, the previous literature has focused on whether senses affects, rather than how they affect. Therefore, the purpose of this thesis is to study how sensory stimuli affects the consumers’ choice of entering physical fashion stores. This thesis is based on sensory marketing, consumer behaviour, and retail marketing...

  19. Franchising as a method of entering the market

    Kolář, Jan

    2008-01-01

    This bachelor thesis deals with franchising as a method of entering the market. My work is divided into theoretical and practical part. In the first part I describe the essential principals of functioning every franchising system. I explain the mutual relationship between franchisor and franchisee and also advantages and disadvantages for both of them. As a next part I mention the importance of using franchising in the world and also in the Czech Republic. Practical part deals with concrete u...

  20. Marketing Strategy : Company X Entering the Australian Wine Market

    Tsukrejev, Jaan

    2014-01-01

    The main objective of this thesis was to identify which marketing strategy is most effective for wine producing companies to enter and compete on the Australian wine market with excessive supply and diminishing demand. The purpose of the thesis was to create a marketing strategy for the commissioner, a case company, referred to as Company X for confidential reasons. Secondary research, predominantly based on marketing literature and governmental statistics, was conducted to create the th...

  1. Vaccines against enteric infections for the developing world.

    Czerkinsky, Cecil; Holmgren, Jan

    2015-06-19

    Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited knowledge regarding the properties of the gut immune system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; -lack of correlates/surrogates of mucosal immune protection; and -limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. [Croatian guidelines for perioperative enteral nutrition of surgical patients].

    Zelić, Marko; Bender, Darija Vranesić; Kelecić, Dina Ljubas; Zupan, Zeljko; Cicvarić, Tedi; Maldini, Branka; Durut, Iva; Rahelić, Velimir; Skegro, Mate; Majerović, Mate; Perko, Zdravko; Sustić, Alan; Madzar, Tomislav; Kovacić, Borna; Kekez, Tihomir; Krznarić, Zeljko

    2014-01-01

    Nutritional status of patients significantly affects the outcome of surgical treatment, whether it's about being obese or malnutrition with loss of muscle mass. Inadequate nutritional support in the perioperative period compromises surgical procedures even in patients who are adequately nourished. In this paper, particular attention was paid to malnourished patients, and their incidence in population hospitalized in surgical wards can be high up to 30%. Special emphasis was paid to the appropriateness of preoperative fasting and to the acceptance of new knowledge in this area of treatment. The aim of this working group was to make guidelines for perioperative nutritional support with different modalities of enteral nutrition. The development of these guidelines was attended by representatives of Croatian Medical Association: Croatian Society for Digestive Surgery, Croatian Society for Clinical Nutrition, Croatian Society of Surgery, Croatian Society for Endoscopic Surgery, Croatian Trauma Society and the Croatian Society of Anesthesiology and Intensive Care. The guidelines are designed as a set of questions that arise daily in clinical practice when preparing patients for surgery and after the surgical treatment, which relate to the assessment of nutritional status, perioperative nutritional support, duration of preoperative fasting period and the selection of food intake route. Assessment of nutritional status and the use of different modes of enteral nutrition should enter into standard protocols of diagnosis and treatment in the Croatian hospitals.

  3. The Challenges of Home Enteral Tube Feeding: A Global Perspective

    Omorogieva Ojo

    2015-04-01

    Full Text Available The aim of this review is to provide a global perspective of Home Enteral Tube Feeding (HETF and to outline some of the challenges of home enteral nutrition (HEN provisions. It is well established that the number of patients on HETF is on the increase worldwide due to advances in technology, development of percutaneous endoscopic gastrostomy techniques, and the shift in care provisions from acute to community settings. While the significance of home enteral nutrition in meeting the nutritional requirements of patients with poor swallowing reflexes and those with poor nutritional status is not in doubt, differences exist in terms of funding, standards, management approaches and the level of infrastructural development across the world. Strategies for alleviating some of the challenges militating against the effective delivery of HETF including the development of national and international standards, guidelines and policies for HETF, increased awareness and funding by government at all levels were discussed. Others, including development of HEN services, which should create the enabling environment for multidisciplinary team work, clinical audit and research, recruitment and retention of specialist staff, and improvement in patient outcomes have been outlined. However, more research is required to fully establish the cost effectiveness of the HEN service especially in developing countries and to compare the organization of HEN service between developing and developed countries.

  4. Enteric virus removal inactivation by coal-based media

    Gupta, A.; Chaudhuri, M. [Indian Institute of Technology, Kanpur (India). Dept. of Civil Engineering

    1995-02-01

    Four coal-based media, viz. alum-pretreated or ferric hydroxide-impregnated Giridih bituminous coal and lignite (alum-GBC, Fe-GBC; alum-lignite and Fe-Lignite) were laboratory tested to assess their potential in removing/inactivating enteric viruses in water. Batch-sorption screening tests, employing a poliovirus-spiked canal water, indicated high poliovirus sorption by Fe-GBC and alum-GBC in a short contact time of 5 min. Based on the results of further batch-sorption tests, using silver incorporated media (alum/Ag-GBC, alum-GBC-Ag and Fe-GBC-Ag), as well as aesthetic water quality consideration and previous findings on removal of coliforms and turbidity, alum/Ag-GBC, alum-GBC and alum-GBC-AG were included in downflow column studies employing poliovirus-spiked canal water. All three media showed potential in removing/inactivating enteric viruses. In a separate column study employing a joint challenge of poliovirus and rotavirus, alum/Ag-GBC removed 59.3-86.5% of the viruses along with more than 99% reduction in indigenous heterotrophic bacteria. Alum/silver-pretreated bituminous coal medium appears promising for use in household water filters in rural areas of the developing world. However, improved medium preparation to further enhance its efficiency is needed; also, its efficacy in removing/inactivating indigenous enteric bacteria, viruses and protozoa has to be ensured and practicalities or economics of application need to be considered.

  5. Glucose, epithelium, and enteric nervous system: dialogue in the dark.

    Pfannkuche, H; Gäbel, G

    2009-06-01

    The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

  6. Navigating Risk When Entering and Participating in a Business Ecosystem

    Derek Smith

    2013-05-01

    Full Text Available Entrepreneurs typically have limited resources during the start-up phase of a business. Business ecosystems are a strategy for entrepreneurs to access and exchange many different aspects of value, resources, and benefits. However, there may be business risks for entering a particular type of ecosystem, and further risks may be encountered after entering and participating in a business ecosystem. These risks are significant and can inhibit a startup's growth. In this article, the literature on business ecosystems is reviewed as it relates to risk to discover insights of relevance to entrepreneurs, top management teams, and business-ecosystem operators. First, the published research is organized into two streams: i risks relating to categories of business ecosystems, and ii risks relating to participating in business ecosystems. Then, the problem is abstracted to develop a potential strategy for managing these risks, which features a pre-entry inspection followed by real-time resource management. Finally, five recommendations are offered for entrepreneurs seeking to enter and participate in business ecosystems.

  7. Biomaterial-Derived Calcium Carbonate Nanoparticles for Enteric Drug Delivery

    Diane Render

    2016-01-01

    Full Text Available Oral drug delivery systems provide the most convenient, noninvasive, readily acceptable alternatives to parenteral systems. In the current work, eggshell-derived calcium carbonate (CaCO3 nanoparticles were used to develop enteric drug delivery system in the form of tablets. CaCO3 nanoparticles were manufactured using top-down ball-milling method and characterized by X-ray diffractometry (XRD and transmission electron microscopy (TEM and loaded with 5-fluorouracil as a model drug. Tablets with varying CaCO3 core and binder compositions were fabricated and coated with Eudragit S100 or Eudragit L100. Suitability for enteric delivery of the tablets was tested by oral administration to rabbits and radiography. Radiograph images showed that the tablet remained in the stomach of the rabbit for up to 3 hours. Further modifications of these biomaterial-derived nanoparticles and the coatings will enable manufacturing of stable formulations for slow or controlled release of pharmaceuticals for enteric delivery.

  8. Vaccines against enteric infections for the developing world

    Czerkinsky, Cecil; Holmgren, Jan

    2015-01-01

    Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: —limited knowledge regarding the properties of the gut immune system during early life;—lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines;—lack of correlates/surrogates of mucosal immune protection; and—limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries.There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. PMID:25964464

  9. Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever.

    Wijedoru, Lalith; Mallett, Sue; Parry, Christopher M

    2017-05-26

    Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence

  10. The natural history of clinically established radiation enteritis

    Galland, R.B.; Spencer, J.

    1985-01-01

    70 patients presenting to a surgical unit with radiation enteritis were followed up. 11 of the 61 who underwent operations died of operation-related causes. The 51 patients who survived for more than 3 months were followed up for up to 12 years (median 12 months). 24 had no further symptoms related to their radiation enteritis. The other 27 patients had persistence of symptoms, post-operative complications, new radiation-related problems, or a combination of these. The twenty new radiation-related problems were stricture (8 patients), malabsorption (5), fistula(1), and miscellaneous(6). These developed in in 12 of 36 patients presenting initially with stricture, compared with 8 of 9 patients presenting with a perforation or fistula (p=0.007 Fisher's exact test) and none whose first symptom was bleeding (p=0.001 vs perforation and fistula combined). 10 of the 27 patients with further problems required operations and 5 of them died. Radiation enteritis is thus a progressive disease, with further complications becoming apparent in about half of those surviving the initial lesion. Perforation or fistula formation indicates a poorer prognosis than does stricture or haemorrhage. (author)

  11. La nutrición enteral precoz en el enfermo grave Early enteral nutrition in the critically-ill patient

    B. García Vila; T. Grau

    2005-01-01

    La nutrición enteral se ha demostrado como un método eficaz y seguro de nutrir a los enfermos graves ingresados en una Unidad de Cuidados Intensivos. Aunque se desconoce cuánto tiempo puede estar un enfermo grave sin nutrición, el catabolismo acelerado y el ayuno pueden ser deletéreos en el enfermo grave y la recomendación más frecuente es la de empezar la nutrición artificial cuando se prevea un período de ayuno superior a los siete días. Las ventajas de la nutrición enteral sobre la nutrici...

  12. Randomized clinical trial of arginine-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing gastric cancer surgery.

    Zhao, Hongyan; Zhao, Hongying; Wang, Yu; Jing, Huang; Ding, Qian; Xue, Jun

    2013-09-01

    Significant malnutrition exists in a high percentage of patients with gastric cancer. It is, therefore, crucial to establish an effective means to provide nutrition for these patients. This prospective, randomized, double-blinded clinical trial aims to assess the long-term survival of arginine-supplementation enteral nutrition versus standard enteral nutrition in malnourished patients with gastric cancer. The control group (36 cases) received postoperative standard enteral nutrition. Meanwhile, the arginine-supplementation group (37 cases) adopted the same nutrition product but enriched with arginine (9.0 g/L). The primary study objective was overall survival (OS). Secondary endpoints were progression-free survival (PFS); serum parameters including total protein, albumin, proalbumin, and transferrin obtained on preoperative day 1, postoperative day 2, and day 12; CD4(+) and CD8(+) T cells, natural killer (NK) cells, immunoglobulin M (IgM), and immunoglobulin G (IgG) obtained on preoperative day 1 and postoperative day 7. No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better OS (P = 0.03, 41 vs. 30.5 months) and better PFS (P = 0.02, 18 vs. 11.5 months). On postoperative day 7, CD4(+) T cells, NK cells, IgM and IgG levels of the arginine-supplemented group increased prominently and were significantly higher than those of the control group and those on preoperative day 1. There is no significant difference in the serum total protein, albumin, proalbumin, and transferrin levels between the two arms. Arginine-supplemented enteral nutrition significantly improves long-term survival and restores immunity in malnourished gastric cancer.

  13. Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.

    Cervantes-Villagrana, Alberto R; Hernández-Pando, Rogelio; Biragyn, Arya; Castañeda-Delgado, Julio; Bodogai, Monica; Martínez-Fierro, Margarita; Sada, Eduardo; Trujillo, Valentin; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

    2013-01-11

    The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0-89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Sustainable Milk and Meat Production while Reducing Methane Emissions from Livestock Enteric Fermentation

    Castelan-Ortega, O. A.; Molina, L. T.; Pedraza-Beltrán, P. E.; Hernández-Pineda, G.; Ku-Vera, J. C.; Benaouda, M.; Gonzalez-Ronquillo, M.

    2016-12-01

    Ruminants produce all the milk and most of the meat demanded by humans; however, ruminant production generates large quantities of greenhouse gases (GHG), around 15% of anthropogenic emissions of GHG are attributed to ruminant production. Therefore there is an urgent need to develop sustainable alternatives to mitigate GHG emissions by ruminants and to increase the supply of high quality protein for human consumption in a climate change scenario. The objective of this work is to present sustainable options to mitigate methane (CH4) production from enteric fermentation by cattle and to illustrate how productivity can be increased at the same time. We conducted several experiments to measure CH4 emission in vivo by cattle in order to estimate emission factors in the temperate and tropical climate regions of Mexico followed by inventory calculation. We then evaluated the supplementation to cattle of different tanniferous plants to reduce enteric CH4 formation and finally established two mitigation scenarios for each region. Leucaena leucocephala and Cosmos bipinnatus are the tanniferous plants that produced the largest reduction in CH4 formation. In scenario 1, a moderate mitigation scenario, it was assumed 16% reduction of enteric CH4 emission in the temperate climate regions (TEMP) and 36% in the tropical regions (TROP) with cattle population of 37.8 million heads, from which 22.3 are in the TEMP (emission factor 529 l/day/head) and 15.5 in the TROP (emission factor 137 l/day/head). Reduction potential resulting from the use of C. bipinnatus and L. Leucocephala over a year is 1,203Gg. In scenario 2, a high mitigation situation, it was assumed a 26% reduction of CH4 emission in the TEMP and 36% in the TROP and the same cattle population. The reduction potential resulting from C. bipinnatus and L. Leucocephala use in a year is 1,512 Gg. Results showed that in both scenarios the CH4 released by enteric fermentation could be reduced by the use of the plants evaluated

  15. Enteral versus parenteral nutrition and enteral versus a combination of enteral and parenteral nutrition for adults in the intensive care unit.

    Lewis, Sharon R; Schofield-Robinson, Oliver J; Alderson, Phil; Smith, Andrew F

    2018-06-08

    Critically ill people are at increased risk of malnutrition. Acute and chronic illness, trauma and inflammation induce stress-related catabolism, and drug-induced adverse effects may reduce appetite or increase nausea and vomiting. In addition, patient management in the intensive care unit (ICU) may also interrupt feeding routines. Methods to deliver nutritional requirements include provision of enteral nutrition (EN), or parenteral nutrition (PN), or a combination of both (EN and PN). However, each method is problematic. This review aimed to determine the route of delivery that optimizes uptake of nutrition. To compare the effects of enteral versus parenteral methods of nutrition, and the effects of enteral versus a combination of enteral and parenteral methods of nutrition, among critically ill adults, in terms of mortality, number of ICU-free days up to day 28, and adverse events. We searched CENTRAL, MEDLINE, and Embase on 3 October 2017. We searched clinical trials registries and grey literature, and handsearched reference lists of included studies and related reviews. We included randomized controlled studies (RCTs) and quasi-randomized studies comparing EN given to adults in the ICU versus PN or versus EN and PN. We included participants that were trauma, emergency, and postsurgical patients in the ICU. Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of evidence with GRADE. We included 25 studies with 8816 participants; 23 studies were RCTs and two were quasi-randomized studies. All included participants were critically ill in the ICU with a wide range of diagnoses; mechanical ventilation status between study participants varied. We identified 11 studies awaiting classification for which we were unable to assess eligibility, and two ongoing studies.Seventeen studies compared EN versus PN, six compared EN versus EN and PN, two were multi-arm studies comparing EN versus PN

  16. Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors.

    Mundell, Nathan A; Plank, Jennifer L; LeGrone, Alison W; Frist, Audrey Y; Zhu, Lei; Shin, Myung K; Southard-Smith, E Michelle; Labosky, Patricia A

    2012-03-15

    The enteric nervous system (ENS) arises from the coordinated migration, expansion and differentiation of vagal and sacral neural crest progenitor cells. During development, vagal neural crest cells enter the foregut and migrate in a rostro-to-caudal direction, colonizing the entire gastrointestinal tract and generating the majority of the ENS. Sacral neural crest contributes to a subset of enteric ganglia in the hindgut, colonizing the colon in a caudal-to-rostral wave. During this process, enteric neural crest-derived progenitors (ENPs) self-renew and begin expressing markers of neural and glial lineages as they populate the intestine. Our earlier work demonstrated that the transcription factor Foxd3 is required early in neural crest-derived progenitors for self-renewal, multipotency and establishment of multiple neural crest-derived cells and structures including the ENS. Here, we describe Foxd3 expression within the fetal and postnatal intestine: Foxd3 was strongly expressed in ENPs as they colonize the gastrointestinal tract and was progressively restricted to enteric glial cells. Using a novel Ednrb-iCre transgene to delete Foxd3 after vagal neural crest cells migrate into the midgut, we demonstrated a late temporal requirement for Foxd3 during ENS development. Lineage labeling of Ednrb-iCre expressing cells in Foxd3 mutant embryos revealed a reduction of ENPs throughout the gut and loss of Ednrb-iCre lineage cells in the distal colon. Although mutant mice were viable, defects in patterning and distribution of ENPs were associated with reduced proliferation and severe reduction of glial cells derived from the Ednrb-iCre lineage. Analyses of ENS-lineage and differentiation in mutant embryos suggested activation of a compensatory population of Foxd3-positive ENPs that did not express the Ednrb-iCre transgene. Our findings highlight the crucial roles played by Foxd3 during ENS development including progenitor proliferation, neural patterning, and glial

  17. Enteric Pathogen-Plant Interactions: Molecular Connections Leading to Colonization and Growth and Implications for Food Safety

    Martínez-Vaz, Betsy M.; Fink, Ryan C.; Diez-Gonzalez, Francisco; Sadowsky, Michael J.

    2014-01-01

    Leafy green vegetables have been identified as a source of foodborne illnesses worldwide over the past decade. Human enteric pathogens, such as Escherichia coli O157:H7 and Salmonella, have been implicated in numerous food poisoning outbreaks associated with the consumption of fresh produce. An understanding of the mechanisms responsible for the establishment of pathogenic bacteria in or on vegetable plants is critical for understanding and ameliorating this problem as well as ensuring the sa...

  18. Genetic aspects of enteric methane emission in ruminants livestock

    Martino Cassandro

    2013-10-01

    Full Text Available This review summarizes the importance of enteric methane (CH4 emission in ruminants and relevant to the current on knowledge relevant to genetic aspects of enteric CH4 production, highlighting future research needs and directions. Global average temperature has increased by about 0.7°C in the last century. The Intergovernmental Panel on Climate Change (IPCC reported that anthropogenic greenhouse gases (GHG, including carbon dioxide (CO2, CH4, nitrous oxide (N2O and halocarbons, have been responsible for most of the observed temperature increase since the middle of the twentieth century. Agriculture, particularly livestock, is increasingly being recognized as both a contributor to the process and a potential victim of it. Policy interventions and technical solutions are required to address both the impact of livestock production on climate change and the effects of climate change on livestock production. Food and Agriculture Organization (FAO, declared that in the next 50 years, the world’s farmers will be called upon to produce more food than has been produced in the past 10,000 years, and to do so in environmentally sustainable ways. Therefore, the GHG reduction should be treated as a public good. The United States congress is prospecting to define a price on GHG emissions. Limiting the concentration of CO2 and other GHG in Earth’s atmosphere requires a technological and economic revolution. A cost-effective way could be the genetic improvement of livestock, which produces permanent and cumulative changes in performance. Animal variation in enteric CH4 emission has been reported in the literature, providing potential for improvement through genetic selection. 

  19. Entering the lesbian world in Japan: debut stories.

    Kamano, Saori

    2005-01-01

    Conceiving of a "lesbian community" as the process and/or the end product of a lesbian's going outside herself or her intimate relationship to connect with other lesbians, this paper explores the experiences of lesbians in entering the community in Tokyo, Japan, which lesbians refer to as "community debut." Based on the personal accounts gathered through interviewing 24 women in 2002 in the Tokyo area, this paper examines the personal contexts in which the women entered a lesbian community, which included searching for and defining themselves, accepting themselves, and acting out the new identity to make changes in their lives. Some of the women interviewed were prompted by a need to understand themselves as lesbians. Others with a lesbian identity searched for further affirmation through connecting with "the world of lesbians" beyond their immediate contexts. For some other women interviewed, entering the community was a way to help them start their lives anew by getting out of their previous (married) lives. The paper also specifically touches on the significance of the Internet as a source of information for individual women and as a way of creating a lesbian community, identifying both positive and negative aspects. Although the research reported in this paper leaves for further exploration how boundaries of the communities are negotiated and drawn, the norms of the communities, and conflicts and negotiations among individuals and groups, it has provided one piece of the mosaic of lesbian communities in Japan. The communities, while still largely invisible in the mainstream society, are nonetheless an important part of life, albeit in different ways, of many lesbians. The research process leads the author to anticipate greater visibility of lesbians and lesbian communities in Japan in the not too distant future.

  20. Clostridial necrotic enteritis in chicken associated with growth rate depression

    Adin Priadi

    2008-03-01

    Full Text Available Clostridium perfringens (C. perfringens is a normal inhabitant of the intestinal tract of chickens as well as a potential pathogen causing necrotic enteritis. C. perfringens only causes necrotic enteritis when it transforms from non-toxin producing type to toxin producing type. The alpha toxin, (phospholipase C is believed to be a key to the occurrence of Clostridial necrotic enteritis (CNE. The best known predisposing factor is mucosal damage, caused by coccidiosis that damages the intestinal lining, making the gut susceptible to infections including C. perfringens. The purpose of this study was to observe the chicken performance in experimental CNE and field cases of CNE. Diagnosis of CNE were made by latex agglutination test, isolation and identification of the agent. Pathological and histopathological changes were also observed. Experimentally, NE could be reproduced when Eimeria sp and C. perfringens spores are inoculated in chicken. Signs of an NE are wet litter and diarrhea, and an increase in mortality is not often obvious. The depression of growth rate and feed efficiency of chicken become noticeable by week 5 because of damage to the intestine and the subsequent reduction in digestion and absorption of food. Subclinical form of CNE was also frequently found in the field, leading to significant decreases in performance. Chicken gut samples examinations revealed that subclinical form of CNE causes damage to the intestinal mucosa caused by C. perfringens leads to decreased digestion and absorption, increased feed conversion ratio and reduced weight gain. Dual infection with C. perfringens and Eimeria sp. was frequently found in field. The results of these studies provide evidence for C. perfringens as a causative bacteria for growth depression.