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Sample records for glucosylating toxins enter

  1. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

    Directory of Open Access Journals (Sweden)

    Carolina Varela Chavez

    2016-03-01

    Full Text Available Clostridium sordellii lethal toxin (TcsL is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases.

  2. Toxin-mediated effects on the innate mucosal defenses: implications for enteric vaccines

    DEFF Research Database (Denmark)

    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...

  3. NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens.

    Directory of Open Access Journals (Sweden)

    Anthony L Keyburn

    2008-02-01

    Full Text Available For over 30 years a phospholipase C enzyme called alpha-toxin was thought to be the key virulence factor in necrotic enteritis caused by Clostridium perfringens. However, using a gene knockout mutant we have recently shown that alpha-toxin is not essential for pathogenesis. We have now discovered a key virulence determinant. A novel toxin (NetB was identified in a C. perfringens strain isolated from a chicken suffering from necrotic enteritis (NE. The toxin displayed limited amino acid sequence similarity to several pore forming toxins including beta-toxin from C. perfringens (38% identity and alpha-toxin from Staphylococcus aureus (31% identity. NetB was only identified in C. perfringens type A strains isolated from chickens suffering NE. Both purified native NetB and recombinant NetB displayed cytotoxic activity against the chicken leghorn male hepatoma cell line LMH; inducing cell rounding and lysis. To determine the role of NetB in NE a netB mutant of a virulent C. perfringens chicken isolate was constructed by homologous recombination, and its virulence assessed in a chicken disease model. The netB mutant was unable to cause disease whereas the wild-type parent strain and the netB mutant complemented with a wild-type netB gene caused significant levels of NE. These data show unequivocally that in this isolate a functional NetB toxin is critical for the ability of C. perfringens to cause NE in chickens. This novel toxin is the first definitive virulence factor to be identified in avian C. perfringens strains capable of causing NE. Furthermore, the netB mutant is the first rationally attenuated strain obtained in an NE-causing isolate of C. perfringens; as such it has considerable vaccine potential.

  4. Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.

    Directory of Open Access Journals (Sweden)

    Chen Sun

    Full Text Available A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs. Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.

  5. Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

    Science.gov (United States)

    Koon, Hon Wai; Ho, Samantha; Hing, Tressia C.; Cheng, Michelle; Chen, Xinhua; Ichikawa, Yoshi; Kelly, Ciarán P.

    2014-01-01

    Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins. PMID:24890583

  6. In ovo vaccines based on recombinant NetB toxin and Montanide IMS adjuvants induced protective immunity against Necrotic Enteritis in chickens

    Science.gov (United States)

    The current study was conducted to investigate the effects of in ovo injection of recombinant clostridium NetB toxin plus Eimeria profilin proteins in combination with Montanide adjuvants in modulating immune system in chickens infected for experimental necrotic enteritis (NE) disease. Broiler eggs ...

  7. T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-γ responses

    International Nuclear Information System (INIS)

    Li Maoxiang; Cuff, Christopher F.; Pestka, James J.

    2006-01-01

    Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity. The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection. Mice were exposed i.p. first to 1.75 mg/kg bw T-2 and then 2 h later with 3 x 10 7 plaque-forming units of reovirus serotype 1, strain Lang (T1/L). As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days. Levels of reovirus λ2 core spike (L2 gene) RNA in feces in T-2-treated mice were significantly higher at 1, 3, 5, and 7 days than controls. T-2 potentiated L2 mRNA expression in a dose-dependent manner with as little as 50 μg/kg of the toxin having a potentiative effect. T-2 exposure transiently suppressed induction of reovirus-specific IgA in feces (6 and 8 days) as well as specific IgA and IgG 2a in serum (5 days). This suppression corresponded to decreased secretion of reovirus-specific IgA and IgG 2a in Peyer's patch (PP) and lamina propria fragment cultures prepared 5 days after infection. T-2 suppressed IFN-γ responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days. Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-γ responses

  8. A segment of 97 amino acids within the translocation domain of Clostridium difficile toxin B is essential for toxicity.

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    Yongrong Zhang

    Full Text Available Clostridium difficile toxin B (TcdB intoxicates target cells by glucosylating Rho GTPases. TcdB (269 kDa consists of at least 4 functional domains including a glucosyltransferase domain (GTD, a cysteine protease domain (CPD, a translocation domain (TD, and a receptor binding domain (RBD. The function and molecular mode of action of the TD, which is the largest segment of TcdB and comprises nearly 50% of the protein, remain largely unknown. Here we show that a 97-amino-acid segment (AA1756 - 1852, designated as ?97 or D97, located in the C-terminus of the TD and adjacent to the RBD, is essential for the cellular activity of TcdB. Deletion of this segment in TcdB (designated as TxB-D97, did not adversely alter toxin enzymatic activities or its cellular binding and uptake capacity. TxB-D97 bound to and entered cells in a manner similar to TcdB holotoxin. Both wild type and mutant toxins released their GTDs similarly in the presence of inositol hexakisphosphate (InsP6, and showed a similar glucosyltransferase activity in a cell-free glucosylating assay. Despite these similarities, the cytotoxic activity of TxB-D97 was reduced by more than 5 logs compared to wild type toxin, supported by the inability of TxB-D97 to glucosylate Rac1 of target cells. Moreover, the mutant toxin failed to elicit tumor necrosis factor alpha (TNF-α in macrophages, a process dependent on the glucosyltransferase activity of the toxin. Cellular fractionation of toxin-exposed cells revealed that TxB-D97 was unable to efficiently release the GTD into cytosol. Thereby, we conclude the 97-amino-acid region of the TD C-terminus of TcdB adjacent to the RBD, is essential for the toxicity of TcdB.

  9. Autoproteolytic Activation of Bacterial Toxins

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    Aimee Shen

    2010-05-01

    Full Text Available Protease domains within toxins typically act as the primary effector domain within target cells. By contrast, the primary function of the cysteine protease domain (CPD in Multifunctional Autoprocessing RTX-like (MARTX and Clostridium sp. glucosylating toxin families is to proteolytically cleave the toxin and release its cognate effector domains. The CPD becomes activated upon binding to the eukaryotic-specific small molecule, inositol hexakisphosphate (InsP6, which is found abundantly in the eukaryotic cytosol. This property allows the CPD to spatially and temporally regulate toxin activation, making it a prime candidate for developing anti-toxin therapeutics. In this review, we summarize recent findings related to defining the regulation of toxin function by the CPD and the development of inhibitors to prevent CPD-mediated activation of bacterial toxins.

  10. Development and Evaluation of Monoclonal Antibodies for the Glucoside of T-2 Toxin (T2-Glc)

    OpenAIRE

    Maragos, Chris M.; Kurtzman, Cletus; Busman, Mark; Price, Neil; McCormick, Susan

    2013-01-01

    The interactions between fungi and plants can yield metabolites that are toxic in animal systems. Certain fungi are known to produce sesquiterpenoid trichothecenes, such as T-2 toxin, that are biotransformed by several mechanisms including glucosylation. The glucosylated forms have been found in grain and are of interest as potential reservoirs of T-2 toxin that are not detected by many analytical methods. Hence the glucosides of trichothecenes are often termed “masked” mycotoxins. The glucos...

  11. Glucosylated polyethylenimine as a tumor-targeting gene carrier.

    Science.gov (United States)

    Park, In-Kyu; Cook, Seung-Eun; Kim, You-Kyoung; Kim, Hyun-Woo; Cho, Myung-Haing; Jeong, Hwan-Jeong; Kim, Eun-Mi; Nah, Jae-Woon; Bom, Hee-Seung; Cho, Chong-Su

    2005-11-01

    Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-%) had no cytotoxic effect on cells even at polymer concentrations higher than 200 microg/mL. Compared to unglucosylated PEI, glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEI. Gamma imaging technique revealed GPEI/DNA complex was distributed in liver, spleen, and tumors.

  12. Nonenzymatic glucosylation of neuronal calmodulin and its functional consequences

    International Nuclear Information System (INIS)

    Kowluru, R.A.; Kowluru, A.; Bitensky, M.W.

    1986-01-01

    Glucosylation (NEG) (nonenzymatic) of proteins is a posttranslational protein modification that occurs readily in the diabetic environment. As a consequence of NEG some proteins are known to undergo a change in function. Their studies of red blood cell (RBC) cytoskeletal proteins indicate that calmodulin is glucosylated in the diabetic RBC and this is followed by a change in function. Here they present new data in support of their earlier findings. Purified bovine brain calmodulin was glucosylated in vitro in the presence of 28 mM glucose. After six days of incubation at room temperature 2.75 moles of glucose were incorporated per mole of calmodulin. Glucosylated calmodulin exhibited a marked reduction in calcium dependent functions. Its ability to stimulate neuronal phosphodiesterase (PDE) and adenylate cyclase was reduced by 65 and 80% respectively. Its ability to stimulate rat brain protein kinase was reduced by 40%. Glucosylated calmodulin exhibited a 56% drop in its 45 Ca binding as compared with unmodified calmodulin. These data provide an additional example in which NEG markedly alters protein function

  13. New insights on glucosylated lipids: metabolism and functions.

    Science.gov (United States)

    Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

    2013-09-01

    Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Recurring Necrotic Enteritis Outbreaks in Commercial Broiler Chicken Flocks Strongly Influence Toxin Gene Carriage and Species Richness in the Resident Clostridium perfringens Population

    Science.gov (United States)

    Gaucher, Marie-Lou; Perron, Gabriel G.; Arsenault, Julie; Letellier, Ann; Boulianne, Martine; Quessy, Sylvain

    2017-01-01

    Extensive use of antibiotic growth promoters (AGPs) in food animals has been questioned due to the globally increasing problem of antibiotic resistance. For the poultry industry, digestive health management following AGP withdrawal in Europe has been a challenge, especially the control of necrotic enteritis. Much research work has focused on gut health in commercial broiler chicken husbandry. Understanding the behavior of Clostridium perfringens in its ecological niche, the poultry barn, is key to a sustainable and cost-effective production in the absence of AGPs. Using polymerase chain reaction and pulsed-field gel electrophoresis, we evaluated how the C. perfringens population evolved in drug-free commercial broiler chicken farms, either healthy or affected with recurring clinical necrotic enteritis outbreaks, over a 14-month period. We show that a high genotypic richness was associated with an increased risk of clinical necrotic enteritis. Also, necrotic enteritis-affected farms had a significant reduction of C. perfringens genotypic richness over time, an increase in the proportion of C. perfringens strains harboring the cpb2 gene, the netB gene, or both. Thus, necrotic enteritis occurrence is correlated with the presence of an initial highly diverse C. perfringens population, increasing the opportunity for the selective sweep of particularly virulent genotypes. Disease outbreaks also appear to largely influence the evolution of this bacterial species in poultry farms over time. PMID:28567032

  15. Recurring Necrotic Enteritis Outbreaks in Commercial Broiler Chicken Flocks Strongly Influence Toxin Gene Carriage and Species Richness in the Resident Clostridium perfringens Population

    Directory of Open Access Journals (Sweden)

    Marie-Lou Gaucher

    2017-05-01

    Full Text Available Extensive use of antibiotic growth promoters (AGPs in food animals has been questioned due to the globally increasing problem of antibiotic resistance. For the poultry industry, digestive health management following AGP withdrawal in Europe has been a challenge, especially the control of necrotic enteritis. Much research work has focused on gut health in commercial broiler chicken husbandry. Understanding the behavior of Clostridium perfringens in its ecological niche, the poultry barn, is key to a sustainable and cost-effective production in the absence of AGPs. Using polymerase chain reaction and pulsed-field gel electrophoresis, we evaluated how the C. perfringens population evolved in drug-free commercial broiler chicken farms, either healthy or affected with recurring clinical necrotic enteritis outbreaks, over a 14-month period. We show that a high genotypic richness was associated with an increased risk of clinical necrotic enteritis. Also, necrotic enteritis-affected farms had a significant reduction of C. perfringens genotypic richness over time, an increase in the proportion of C. perfringens strains harboring the cpb2 gene, the netB gene, or both. Thus, necrotic enteritis occurrence is correlated with the presence of an initial highly diverse C. perfringens population, increasing the opportunity for the selective sweep of particularly virulent genotypes. Disease outbreaks also appear to largely influence the evolution of this bacterial species in poultry farms over time.

  16. Recurring Necrotic Enteritis Outbreaks in Commercial Broiler Chicken Flocks Strongly Influence Toxin Gene Carriage and Species Richness in the Resident Clostridium perfringens Population.

    Science.gov (United States)

    Gaucher, Marie-Lou; Perron, Gabriel G; Arsenault, Julie; Letellier, Ann; Boulianne, Martine; Quessy, Sylvain

    2017-01-01

    Extensive use of antibiotic growth promoters (AGPs) in food animals has been questioned due to the globally increasing problem of antibiotic resistance. For the poultry industry, digestive health management following AGP withdrawal in Europe has been a challenge, especially the control of necrotic enteritis. Much research work has focused on gut health in commercial broiler chicken husbandry. Understanding the behavior of Clostridium perfringens in its ecological niche, the poultry barn, is key to a sustainable and cost-effective production in the absence of AGPs. Using polymerase chain reaction and pulsed-field gel electrophoresis, we evaluated how the C. perfringens population evolved in drug-free commercial broiler chicken farms, either healthy or affected with recurring clinical necrotic enteritis outbreaks, over a 14-month period. We show that a high genotypic richness was associated with an increased risk of clinical necrotic enteritis. Also, necrotic enteritis-affected farms had a significant reduction of C. perfringens genotypic richness over time, an increase in the proportion of C. perfringens strains harboring the cpb2 gene, the netB gene, or both. Thus, necrotic enteritis occurrence is correlated with the presence of an initial highly diverse C. perfringens population, increasing the opportunity for the selective sweep of particularly virulent genotypes. Disease outbreaks also appear to largely influence the evolution of this bacterial species in poultry farms over time.

  17. Recurring Necrotic Enteritis Outbreaks in Commercial Broiler Chicken Flocks Strongly Influence Toxin Gene Carriage and Species Richness in the Resident Clostridium perfringens Population

    OpenAIRE

    Marie-Lou Gaucher; Marie-Lou Gaucher; Marie-Lou Gaucher; Gabriel G. Perron; Julie Arsenault; Ann Letellier; Martine Boulianne; Sylvain Quessy

    2017-01-01

    Extensive use of antibiotic growth promoters (AGPs) in food animals has been questioned due to the globally increasing problem of antibiotic resistance. For the poultry industry, digestive health management following AGP withdrawal in Europe has been a challenge, especially the control of necrotic enteritis. Much research work has focused on gut health in commercial broiler chicken husbandry. Understanding the behavior of Clostridium perfringens in its ecological niche, the poultry barn, is k...

  18. Stool C difficile toxin

    Science.gov (United States)

    ... toxin; Colitis - toxin; Pseudomembranous - toxin; Necrotizing colitis - toxin; C difficile - toxin ... be analyzed. There are several ways to detect C difficile toxin in the stool sample. Enzyme immunoassay ( ...

  19. The catalytic potency of ß-glucosidase from Pyroccus furiosus in the direct glucosylation reaction

    NARCIS (Netherlands)

    Roode, de B.M.; Meer, van der T.D.; Kaper, T.; Franssen, M.C.R.; Padt, van der A.; Oost, van der J.; Boom, R.M.

    2001-01-01

    Enzymes from extremophiles operate at conditions that are different from their `normal' counterparts, and are therefore a useful extension of the enzyme toolbox. In this paper, the direct glucosylation reaction mediated by a hyperthermophilic -glucosidase from Pyrocuccus furiosus was investigated.

  20. Structural analysis of rebaudioside A derivatives obtained by Lactobacillus reuteri 180 glucansucrase-catalyzed trans-α-glucosylation

    NARCIS (Netherlands)

    Gerwig, Gerrit J; Te Poele, Evelien M; Dijkhuizen, Lubbert; Kamerling, Johannis P

    2017-01-01

    The wild-type Gtf180-ΔN glucansucrase enzyme from Lactobacillus reuteri 180 was found to catalyze the α-glucosylation of the steviol glycoside rebaudioside A, using sucrose as glucosyl donor in a transglucosylation process. Structural analysis of the formed products by MALDI-TOF mass spectrometry,

  1. Enteric glia.

    Science.gov (United States)

    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.

  2. Asymmetric synthesis of cyclo-archaeol and ß-glucosyl cyclo-archaeol

    NARCIS (Netherlands)

    Ferrer, C.; Fodran, P.; Barroso, S.; Gibson, R.; Hopmans, E.C.; Sinninghe Damsté, J.S.; Schouten, S.; Minnaard, A.J.

    2013-01-01

    An efficient asymmetric synthesis of cyclo-archaeol and beta-glucosyl cyclo-archaeol is presented employing catalytic asymmetric conjugate addition and catalytic epoxide ring opening as the key steps. Their occurrence in deep sea hydrothermal vents has been confirmed by chromatographic comparison

  3. O-Glucosylation of cis-Zeatin in Maize. Characterization of Genes, Enzymes, and Endogenous Cytokinins

    Czech Academy of Sciences Publication Activity Database

    Veach, Y. K.; Martin, R. C.; Mok, D. W. S.; Malbeck, Jiří; Vaňková, Radomíra; Mok, M. C.

    2003-01-01

    Roč. 131, č. 3 (2003), s. 1374-1380 ISSN 0032-0889 R&D Projects: GA MŠk ME 406 Institutional research plan: CEZ:AV0Z5038910 Keywords : Cis-cytokinin * O-glucosylation * Zea Mays Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.634, year: 2003

  4. Chemo-enzymatic synthesis route to poly(glucosyl-acrylates) using glucosidase from almonds

    NARCIS (Netherlands)

    Kloosterman, Wouter M. J.; Roest, Steven; Priatna, Siti R.; Stavila, Erythrina; Loos, Katja

    2014-01-01

    Novel types of glucosyl-acrylate monomers are obtained by beta-glucosidase from almond catalyzed glycosidation reaction. The saccharide-acrylate monomers were synthesized by reaction of D-glucose with hydroxyl functional acrylates: 2-hydroxyethyl acrylate (2-HEA), 2-hydroxyethyl methacrylate

  5. The role of toxins in Clostridium difficile infection.

    Science.gov (United States)

    Chandrasekaran, Ramyavardhanee; Lacy, D Borden

    2017-11-01

    Clostridium difficile is a bacterial pathogen that is the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. The incidence, severity, mortality and healthcare costs associated with C. difficile infection (CDI) are rising, making C. difficile a major threat to public health. Traditional treatments for CDI involve use of antibiotics such as metronidazole and vancomycin, but disease recurrence occurs in about 30% of patients, highlighting the need for new therapies. The pathogenesis of C. difficile is primarily mediated by the actions of two large clostridial glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a third toxin, the binary toxin C. difficile transferase, which can also contribute to C. difficile virulence and disease. These toxins act on the colonic epithelium and immune cells and induce a complex cascade of cellular events that result in fluid secretion, inflammation and tissue damage, which are the hallmark features of the disease. In this review, we summarize our current understanding of the structure and mechanism of action of the C. difficile toxins and their role in disease. Published by Oxford University Press on behalf of FEMS 2017.

  6. Polyamine toxins

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Jensen, Lars S; Vogensen, Stine B

    2005-01-01

    Polyamine toxins, isolated from spiders and wasps, have been used as pharmacological tools for the study of ionotropic receptors, but their use have so far been hampered by their lack of selectivity. In this mini-review, we describe how careful synthetic modification of native polyamine toxins ha...

  7. Radiation enteritis

    International Nuclear Information System (INIS)

    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.)

  8. Enteric Duplication.

    Science.gov (United States)

    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.

  9. Relative disease susceptibility and clostridial toxin antibody responses in three commercial broiler lines co-infected with Clostridium perfringens and Eimeria maxima using an experimental model of necrotic enteritis

    Science.gov (United States)

    Necrotic enteritis is an enteric disease of poultry resulting from infection by Clostridium perfringens with co-infection by Eimeria spp. constituting a major risk factor for disease pathogenesis. This study compared three commercial broiler chicken lines using an experimental model of necrotic ente...

  10. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Science.gov (United States)

    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...

  11. Botulinum toxin

    Directory of Open Access Journals (Sweden)

    Nigam P

    2010-01-01

    Full Text Available Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C 1 , C 2 , D, E, F and G. All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice.

  12. Radiation enteritis

    International Nuclear Information System (INIS)

    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.)

  13. Benzoxazolinone detoxification by N-Glucosylation: The multi-compartment-network of Zea mays L.

    Science.gov (United States)

    Schulz, Margot; Filary, Barbara; Kühn, Sabine; Colby, Thomas; Harzen, Anne; Schmidt, Jürgen; Sicker, Dieter; Hennig, Lothar; Hofmann, Diana; Disko, Ulrich; Anders, Nico

    2016-01-01

    The major detoxification product in maize roots after 24 h benzoxazolin-2(3H)-one (BOA) exposure was identified as glucoside carbamate resulting from rearrangement of BOA-N-glucoside, but the pathway of N-glucosylation, enzymes involved and the site of synthesis were previously unknown. Assaying whole cell proteins revealed the necessity of H2O2 and Fe(2+) ions for glucoside carbamate production. Peroxidase produced BOA radicals are apparently formed within the extraplastic space of the young maize root. Radicals seem to be the preferred substrate for N-glucosylation, either by direct reaction with glucose or, more likely, the N-glucoside is released by glucanase/glucosidase catalyzed hydrolysis from cell wall components harboring fixed BOA. The processes are accompanied by alterations of cell wall polymers. Glucoside carbamate accumulation could be suppressed by the oxireductase inhibitor 2-bromo-4´-nitroacetophenone and by peroxidase inhibitor 2,3-butanedione. Alternatively, activated BOA molecules with an open heterocycle may be produced by microorganisms (e.g., endophyte Fusarium verticillioides) and channeled for enzymatic N-glucosylation. Experiments with transgenic Arabidopsis lines indicate a role of maize glucosyltransferase BX9 in BOA-N-glycosylation. Western blots with BX9 antibody demonstrate the presence of BX9 in the extraplastic space. Proteomic analyses verified a high BOA responsiveness of multiple peroxidases in the apoplast/cell wall. BOA incubations led to shifting, altered abundances and identities of the apoplast and cell wall located peroxidases, glucanases, glucosidases and glutathione transferases (GSTs). GSTs could function as glucoside carbamate transporters. The highly complex, compartment spanning and redox-regulated glucoside carbamate pathway seems to be mainly realized in Poaceae. In maize, carbamate production is independent from benzoxazinone synthesis.

  14. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

    Science.gov (United States)

    Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

    2007-03-01

    When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

  15. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria.

    Directory of Open Access Journals (Sweden)

    Carsten Schwan

    2009-10-01

    Full Text Available Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B. Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT (Clostridium difficile transferase, which ADP-ribosylates actin and inhibits actin polymerization. Thus far, the role of CDT as a virulence factor is not understood. Here we report by using time-lapse- and immunofluorescence microscopy that CDT and other binary actin-ADP-ribosylating toxins, including Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin, induce redistribution of microtubules and formation of long (up to >150 microm microtubule-based protrusions at the surface of intestinal epithelial cells. The toxins increase the length of decoration of microtubule plus-ends by EB1/3, CLIP-170 and CLIP-115 proteins and cause redistribution of the capture proteins CLASP2 and ACF7 from microtubules at the cell cortex into the cell interior. The CDT-induced microtubule protrusions form a dense meshwork at the cell surface, which wrap and embed bacterial cells, thereby largely increasing the adherence of Clostridia. The study describes a novel type of microtubule structure caused by less efficient microtubule capture and offers a new perspective for the pathogenetic role of CDT and other binary actin-ADP-ribosylating toxins in host-pathogen interactions.

  16. Synthesis of C-Glucosylated Octaketide Anthraquinones in Nicotiana benthamiana by Using a Multispecies-Based Biosynthetic Pathway

    DEFF Research Database (Denmark)

    Andersen-Ranberg, Johan; Kongstad, Kenneth Thermann; Nafisi, Majse

    2017-01-01

    unsuccessful. Herein, a novel combination of enzymes derived from a plant (Aloe arborescens, Aa), a bacterium (Streptomyces sp. R1128, St), and an insect (Dactylopius coccus, Dc) that allows for the biosynthesis of the C-glucosylated anthraquinone, dcII, a precursor for carminic acid, is reported. The pathway...

  17. Structural characterization of glucosylated lactose derivatives synthesized by the Lactobacillus reuteri GtfA and Gtf180 glucansucrase enzymes.

    Science.gov (United States)

    Pham, Hien T T; Dijkhuizen, Lubbert; van Leeuwen, Sander S

    2017-09-08

    Glucansucrase enzymes from lactic acid bacteria are receiving strong interest because of their wide range of gluco-oligosaccharide and polysaccharide products from sucrose, some of which have prebiotic potential. Glucansucrases GtfA and Gtf180 from Lactobacillus reuteri strains are known to convert sucrose into α-glucans with different types of linkages, but also to use other molecules as acceptor substrates. Here we report that incubation of (N-terminally truncated versions of) these enzymes with lactose plus sucrose resulted in synthesis of at least 5 glucosylated lactose products of a degree of polymerization (DP) of 3-4. Only glucansucrase Gtf180-ΔN also produced larger lactose-based oligosaccharides (up to DP9). Structural characterization of the glucosylated lactose products DP3-4 revealed glycosidic bonds other than (α1→4)/(α1→6) typical for GtfA-ΔN and (α1→3)/(α1→6) typical for Gtf180-ΔN: Both GtfA-ΔN and Gtf180-ΔN now introduced a glucosyl residue (α1→3)- or (α1→4)-linked to the non-reducing galactose unit of lactose. Both enzymes also were able to introduce a glucosyl residue (α1→2)-linked to the reducing glucose unit of lactose. These lactose derived oligosaccharides potentially are interesting prebiotic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains

    Directory of Open Access Journals (Sweden)

    Lara-Antonia Beer

    2018-06-01

    Full Text Available Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum, the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile. All these binary toxins have ADP-ribosyltransferases (ADPRT as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin was intensively described as a tool for intracellular delivery of allogenic ADPRTs. Here, we firstly describe the binary toxin CDT from C. difficile as an effective tool for heterologous intracellular delivery. Even 60 kDa glucosyltransferase domains of large clostridial glucosyltransferases can be delivered into cells. The glucosyltransferase domains of five tested large clostridial glucosyltransferases were successfully introduced into cells as chimeric fusions to the CDTa adapter domain (CDTaN. Cell uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N-terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains.

  19. Extending the Glucosyl Ceramide Cassette Approach: Application in the Total Synthesis of Ganglioside GalNAc-GM1b

    Directory of Open Access Journals (Sweden)

    Miku Konishi

    2013-12-01

    Full Text Available The development of a novel cyclic glucosyl ceramide cassette acceptor for efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB groups were selected as protecting groups at C2 and C3 of the glucose residue with the aim of improving the functionality of the cassette acceptor. The choice of the PMB group resulted in a loss of β-selectivity, which was corrected by using an appropriate tether to control the spatial arrangement and the nitrile solvent effect. To investigate the effect of linker structure on the β-selectivity of intramolecular glycosylation, several linkers for tethering the glucose and ceramide moiety were designed and prepared, namely, succinyl, glutaryl, dimethylmalonyl, and phthaloyl esters. The succinyl ester linker was the best for accessing the cassette form. The newly designed glucosyl ceramide cassette acceptor was then applied in the total synthesis of ganglioside GalNAc-GM1b.

  20. Botulinum toxin injection - larynx

    Science.gov (United States)

    Injection laryngoplasty; Botox - larynx: spasmodic dysphonia-BTX; Essential voice tremor (EVT)-btx; Glottic insufficiency; Percutaneous electromyography - guided botulinum toxin treatment; Percutaneous indirect laryngoscopy - guided botulinum toxin treatment; ...

  1. Defense against Toxin Weapons

    National Research Council Canada - National Science Library

    Franz, David

    1998-01-01

    .... We typically fear what we do not understand. Although un- derstanding toxin poisoning is less useful in a toxin attack than knowledge of cold injury on an Arctic battlefield, information on any threat reduces its potential to harm...

  2. Clostridial Binary Toxins: Iota and C2 Family Portraits

    Science.gov (United States)

    Stiles, Bradley G.; Wigelsworth, Darran J.; Popoff, Michel R.; Barth, Holger

    2011-01-01

    There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C. perfringens, and C. spiroforme, cause enteric problems in animals as well as humans. These often fatal diseases can partly be attributed to binary protein toxins that follow a classic AB paradigm. Within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-ADP-ribosylation of globular actin by the A component. However, much less is known about B component binding to cell-surface receptors. These toxins share sequence homology amongst themselves and with those produced by another Gram-positive, spore-forming bacterium also commonly associated with soil and disease: Bacillus anthracis. This review focuses upon the iota and C2 families of clostridial binary toxins and includes: (1) basics of the bacterial source; (2) toxin biochemistry; (3) sophisticated cellular uptake machinery; and (4) host–cell responses following toxin-mediated disruption of the cytoskeleton. In summary, these protein toxins aid diverse enteric species within the genus Clostridium. PMID:22919577

  3. Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models.

    Science.gov (United States)

    Tian, Jing-Hui; Glenn, Gregory; Flyer, David; Zhou, Bin; Liu, Ye; Sullivan, Eddie; Wu, Hua; Cummings, James F; Elllingsworth, Larry; Smith, Gale

    2017-07-24

    Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C. difficile (B1/NAP1/027) have emerged and are linked to an increase in morbidity and mortality. Increased virulence is attributed to multiple factors including: increased production of A- and B-toxins; production of binary toxin (CDT); and the emergence of more toxic TcdB variants (TcdB (027) ). TcdB (027) is more cytotoxicity to cells; causes greater tissue damage and toxicity in animals; and is antigenically distinct from historical TcdB (TcdB (003) ). Broadly protective vaccines and therapeutic antibody strategies, therefore, may target TcdA, TcdB variants and CDT. To facilitate the generation of multivalent toxin-based C. difficile vaccines and therapeutic antibodies, we have generated fusion proteins constructed from the receptor binding domains (RBD) of TcdA, TcdB (003) , TcdB (027) and CDT. Herein, we describe the development of a trivalent toxin (T-toxin) vaccine (CDTb/TcdB (003) /TcdA) and quadravalent toxin (Q-toxin) vaccine (CDTb/TcB (003) /TcdA/TcdB (027) ) fusion proteins that retain the protective toxin neutralizing epitopes. Active immunization of mice or hamsters with T-toxin or Q-toxin fusion protein vaccines elicited the generation of toxin neutralizing antibodies to each of the toxins. Hamsters immunized with the Q-toxin vaccine were broadly protected against spore challenge with historical C. difficile 630 (toxinotype 0/ribotype 003) and epidemic NAP1 (toxinotype III/ribotype 027) strains. Fully human polyclonal antitoxin IgG was produced by immunization of transgenic bovine with these fusion proteins. In passive transfer studies, mice were protected against lethal toxin challenge. Hamsters treated with human antitoxin IgG were completely protected when

  4. Bioterrorism: toxins as weapons.

    Science.gov (United States)

    Anderson, Peter D

    2012-04-01

    The potential for biological weapons to be used in terrorism is a real possibility. Biological weapons include infectious agents and toxins. Toxins are poisons produced by living organisms. Toxins relevant to bioterrorism include ricin, botulinum, Clostridium perfrigens epsilson toxin, conotoxins, shigatoxins, saxitoxins, tetrodotoxins, mycotoxins, and nicotine. Toxins have properties of biological and chemical weapons. Unlike pathogens, toxins do not produce an infection. Ricin causes multiorgan toxicity by blocking protein synthesis. Botulinum blocks acetylcholine in the peripheral nervous system leading to muscle paralysis. Epsilon toxin damages cell membranes. Conotoxins block potassium and sodium channels in neurons. Shigatoxins inhibit protein synthesis and induce apoptosis. Saxitoxin and tetrodotoxin inhibit sodium channels in neurons. Mycotoxins include aflatoxins and trichothecenes. Aflatoxins are carcinogens. Trichothecenes inhibit protein and nucleic acid synthesis. Nicotine produces numerous nicotinic effects in the nervous system.

  5. Comparison of α-glucosyl hesperidin of citrus fruits and epigallocatechin gallate of green tea on the Loss of Rotavirus Infectivity in Cell Culture.

    Science.gov (United States)

    Lipson, Steven M; Ozen, Fatma S; Louis, Samantha; Karthikeyan, Laina

    2015-01-01

    A number of secondary plant metabolites (e.g., flavonoids) possess antiviral/antimicrobial activity. Most flavonoids, however, are difficult to study, as they are immiscible in water-based systems. The relatively new semisynthetic α-glucosyl hesperitin (GH), and the natural plant product epigallocatechin gallate (EGCG) are unique among most flavonoids, as these flavonoids are highly soluble. The antiviral activity of these plant metabolites were investigated using the rotavirus as a model enteric virus system. Direct loss of virus structural integrity in cell-free suspension and titration of amplified RTV in host cell cultures was measured by a quantitative enzyme-linked immunosorbent assay (qEIA). After 30 min. 100 × 10(3) μg/ml GH reduced RTV antigen levels by ca. 90%. The same compound reduced infectivity (replication in cell culture) by a similar order of magnitude 3 to 4 days post inoculation. After 3 days in culture, EGCG concentrations of 80, 160, and 320 μg/ml reduced RTV infectivity titer levels to ca. 50, 20, and 15% of the control, respectively. Loss of RTV infectivity titers occurred following viral treatment by parallel testing of both GH and EGCG, with the latter, markedly more effective. Cytotoxicity testing showed no adverse effects by the phenolic concentrations used in this study. The unique chemical structure of each flavonoid rather than each phenolic's inherent solubility may be ascribed to those marked differences between each molecule's antiviral (anti-RTV) effects. The solubility of EGCG and GH obviated our need to use potentially confounding or obfuscating carrier molecules (e.g., methanol, ethanol, DMSO) denoting our use of a pure system environ. Our work further denotes the need to address the unique chemical nature of secondary plant metabolites before any broad generalizations in flavonoid (antiviral) activity may be proposed.

  6. Radiolabelling of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Santos, R.G.; Neves, Nicoli M.J. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil); Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L. [Ouro Preto Univ., MG (Brazil). Escola de Farmacia. Lab. de Fisiologia e Bioquimica de Microorganismos; Lima, M.E. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Bioquimica e Imunologia; Nicoli, J.R. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Microbiologia

    1999-11-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na {sup 125} I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The {sup 125} I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author) 5 refs., 3 figs.; e-mail: nevesmj at urano.cdtn.br

  7. Radiolabelling of cholera toxin

    International Nuclear Information System (INIS)

    Santos, R.G.; Neves, Nicoli M.J.; Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L.; Lima, M.E. de; Nicoli, J.R.

    1999-01-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na 125 I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The 125 I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author)

  8. Enteral nutrition in surgery

    International Nuclear Information System (INIS)

    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)

  9. Crystal structure of Clostridium difficile toxin A

    Energy Technology Data Exchange (ETDEWEB)

    Chumbler, Nicole M.; Rutherford, Stacey A.; Zhang, Zhifen; Farrow, Melissa A.; Lisher, John P.; Farquhar, Erik; Giedroc, David P.; Spiller, Benjamin W.; Melnyk, Roman A.; Lacy, D. Borden

    2016-01-11

    Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and necrosis within the colon. The toxins are large (308 and 270 kDa, respectively), homologous (47% amino acid identity) glucosyltransferases that target small GTPases within the host. The multidomain toxins enter cells by receptor-mediated endocytosis and, upon exposure to the low pH of the endosome, insert into and deliver two enzymatic domains across the membrane. Eukaryotic inositol-hexakisphosphate (InsP6) binds an autoprocessing domain to activate a proteolysis event that releases the N-terminal glucosyltransferase domain into the cytosol. Here, we report the crystal structure of a 1,832-amino-acid fragment of TcdA (TcdA1832), which reveals a requirement for zinc in the mechanism of toxin autoprocessing and an extended delivery domain that serves as a scaffold for the hydrophobic α-helices involved in pH-dependent pore formation. A surface loop of the delivery domain whose sequence is strictly conserved among all large clostridial toxins is shown to be functionally important, and is highlighted for future efforts in the development of vaccines and novel therapeutics.

  10. [Intoxication of botulinum toxin].

    Science.gov (United States)

    Chudzicka, Aleksandra

    2015-09-01

    Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon. © 2015 MEDPRESS.

  11. Synthesis of C-Glucosylated Octaketide Anthraquinones in Nicotiana benthamiana by Using a Multispecies-Based Biosynthetic Pathway.

    Science.gov (United States)

    Andersen-Ranberg, Johan; Kongstad, Kenneth Thermann; Nafisi, Majse; Staerk, Dan; Okkels, Finn Thyge; Mortensen, Uffe Hasbro; Lindberg Møller, Birger; Frandsen, Rasmus John Normand; Kannangara, Rubini

    2017-10-05

    Carminic acid is a C-glucosylated octaketide anthraquinone and the main constituent of the natural dye carmine (E120), possessing unique coloring, stability, and solubility properties. Despite being used since ancient times, longstanding efforts to elucidate its route of biosynthesis have been unsuccessful. Herein, a novel combination of enzymes derived from a plant (Aloe arborescens, Aa), a bacterium (Streptomyces sp. R1128, St), and an insect (Dactylopius coccus, Dc) that allows for the biosynthesis of the C-glucosylated anthraquinone, dcII, a precursor for carminic acid, is reported. The pathway, which consists of AaOKS, StZhuI, StZhuJ, and DcUGT2, presents an alternative biosynthetic approach for the production of polyketides by using a type III polyketide synthase (PKS) and tailoring enzymes originating from a type II PKS system. The current study showcases the power of using transient expression in Nicotiana benthamiana for efficient and rapid identification of functional biosynthetic pathways, including both soluble and membrane-bound enzymes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Cellular Uptake of the Clostridium perfringens Binary Iota-Toxin

    Science.gov (United States)

    Blöcker, Dagmar; Behlke, Joachim; Aktories, Klaus; Barth, Holger

    2001-01-01

    The binary iota-toxin is produced by Clostridium perfringens type E strains and consists of two separate proteins, the binding component iota b (98 kDa) and an actin-ADP-ribosylating enzyme component iota a (47 kDa). Iota b binds to the cell surface receptor and mediates the translocation of iota a into the cytosol. Here we studied the cellular uptake of iota-toxin into Vero cells. Bafilomycin A1, but not brefeldin A or nocodazole, inhibited the cytotoxic effects of iota-toxin, indicating that toxin is translocated from an endosomal compartment into the cytoplasm. Acidification (pH ≤ 5.0) of the extracellular medium enabled iota a to directly enter the cytosol in the presence of iota b. Activation by chymotrypsin induced oligomerization of iota b in solution. An average mass of 530 ± 28 kDa for oligomers was determined by analytical ultracentrifugation, indicating heptamer formation. The entry of iota-toxin into polarized CaCo-2 cells was studied by measuring the decrease in transepithelial resistance after toxin treatment. Iota-toxin led to a significant decrease in resistance when it was applied to the basolateral surface of the cells but not following application to the apical surface, indicating a polarized localization of the iota-toxin receptor. PMID:11292715

  13. Isolation, genotyping, and antimicrobial resistance of zoonotic shiga toxin-producing escherichia coli

    Science.gov (United States)

    Shiga toxin-producing Escherichia coli (STEC) is an enteric pathogen linked to outbreaks of human gastroenteritis with diverse clinical spectra. Traditional culture and isolation methods, including selective enrichment and differential plating, have enabled the effective recovery of STEC. Ruminants ...

  14. Immediate preoperative enteral nutrition (preoperative enteral nutrition

    Directory of Open Access Journals (Sweden)

    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.

  15. A role for arabinogalactan-proteins in plant cell expansion: evidence from studies on the interaction of ß-glucosyl Yariv reagent with seedlings of Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Willats, William George Tycho; Knox, J.P.

    1996-01-01

    Seedlings of Arabidopsis thaliana were germinated and grown in medium containing ß-glucosyl Yariv reagent (ßGlcY), a synthetic phenyl glycoside that interacts specifically with arabinogalactan-proteins (AGPs), a class of plant cell surface proteoglycans. The effect of ßGlcY on the seedlings...

  16. Microalgal toxin(s): characteristics and importance

    African Journals Online (AJOL)

    Prokaryotic and eukaryotic microalgae produce a wide array of compounds with biological activities. These include antibiotics, algicides, toxins, pharmaceutically active compounds and plant growth regulators. Toxic microalgae, in this sense, are common only among the cyanobacteria and dinoflagellates. The microalgal ...

  17. Genetics of enteric neuropathies

    NARCIS (Netherlands)

    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

  18. Fucosylation and protein glycosylation create functional receptors for cholera toxin

    DEFF Research Database (Denmark)

    Wands, Amberlyn M; Fujita, Akiko; McCombs, Janet E

    2015-01-01

    Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we...... in normal human intestinal epithelia and could play a role in cholera....

  19. Enzymatic and structural characterization of hydrolysis of gibberellin A4 glucosyl ester by a rice β-D-glucosidase.

    Science.gov (United States)

    Hua, Yanling; Sansenya, Sompong; Saetang, Chiraporn; Wakuta, Shinji; Ketudat Cairns, James R

    2013-09-01

    In order to identify a rice gibberellin ester β-D-glucosidase, gibberellin A4 β-D-glucosyl ester (GA4-GE) was synthesized and used to screen rice β-glucosidases. Os3BGlu6 was found to have the highest hydrolysis activity to GA4-GE among five recombinantly expressed rice glycoside hydrolase family GH1 enzymes from different phylogenic clusters. The kinetic parameters of Os3BGlu6 and its mutants E178Q, E178A, E394D, E394Q and M251N for hydrolysis of p-nitrophenyl β-D-glucopyranoside (pNPGlc) and GA4-GE confirmed the roles of the catalytic acid/base and nucleophile for hydrolysis of both substrates and suggested M251 contributes to binding hydrophobic aglycones. The activities of the Os3BGlu6 E178Q and E178A acid/base mutants were rescued by azide, which they transglucosylate to produce β-D-glucopyranosyl azide, in a pH-dependent manner, while acetate also rescued Os3BGlu6 E178A at low pH. High concentrations of sodium azide (200-400 mM) inhibited Os3BGlu6 E178Q but not Os3BGlu6 E178A. The structures of Os3BGlu6 E178Q crystallized with either GA4-GE or pNPGlc had a native α-D-glucosyl moiety covalently linked to the catalytic nucleophile, E394, which showed the hydrogen bonding to the 2-hydroxyl in the covalent intermediate. These data suggest that a GH1 β-glucosidase uses the same retaining catalytic mechanism to hydrolyze 1-O-acyl glucose ester and glucoside. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Occurrence and sequestration of toxins in food chains.

    Science.gov (United States)

    Mebs, D

    1998-11-01

    Animals may acquire toxicity by absorbing toxic compounds from their food, e.g. from plants or other animals. Sequestration and accumulation of toxins may provide protection from predators, which learn to avoid this prey because of unpleasant experiences such as bitter taste. This is a common phenomenon in marine as well as in terrestrial ecosystems. Moreover, toxins may enter food chains where they accumulate reaching high, often lethal concentrations. Palytoxin which had been primarily detected in marine zoanthids (Palythoa sp.), occurs also in a wide range of other animals, e.g. in sponges, corals, shellfish, polychaetes and crustaceans, but also in fish, which feed on crustaceans and zoanthids as well. These animals exhibit a high resistance to the toxin's action. The mechanisms which protect the Na+, K+-ATPase of their cell membranes, the primary target of palytoxin, is unknown. Sequestration of the toxin by other animals may cause health problems due to food poisoning.

  1. Topical botulinum toxin.

    Science.gov (United States)

    Collins, Ashley; Nasir, Adnan

    2010-03-01

    Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

  2. Effects of Clostridium perfringens iota toxin in the small intestine of mice.

    Science.gov (United States)

    Redondo, Leandro M; Redondo, Enzo A; Dailoff, Gabriela C; Leiva, Carlos L; Díaz-Carrasco, Juan M; Bruzzone, Octavio A; Cangelosi, Adriana; Geoghegan, Patricia; Fernandez-Miyakawa, Mariano E

    2017-12-01

    Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases. Published by Elsevier Ltd.

  3. Marine and freshwater toxins.

    Science.gov (United States)

    Hungerford, James M

    2006-01-01

    In a very busy and exciting year, 2005 included First Action approval of a much needed official method for paralytic shellfish toxins and multiple international toxin symposia highlighted by groundbreaking research. These are the first-year milestones and activities of the Marine and Freshwater Toxins Task Force and Analytical Community. Inaugurated in 2004 and described in detail in last year's General Referee Report (1) this international toxins group has grown to 150 members from many regions and countries. Perhaps most important they are now making important and global contributions to food safety and to providing alternatives to animal-based assays. Official Method 2005.06 was first approved in late 2004 by the Task Force and subsequently Official First Action in 2005 (2) by the Methods Committee on Natural Toxins and Food Allergens and the Official Methods Board. This nonproprietary method (3) is a precolumn oxidation, liquid chromatographic method that makes good use of fluorescence detection to provide high sensitivity detection of the saxitoxins. It has also proven to be rugged enough for regulatory use and the highest level of validation. As pointed out in the report of method principle investigator and Study Director James Lawrence, approval of 2005.06 now provides the first official alternative to the mouse bioassay after many decades of shellfish monitoring. This past year in April 2005 the group also held their first international conference, "Marine and Freshwater Toxins Analysis: Ist Joint Symposium and AOAC Task Force Meeting," in Baiona, Spain. The 4-day conference consisted of research and stakeholder presentations and symposium-integrated subgroup sessions on ciguatoxins, saxitoxin assays and liquid chromatography (LC) methods for saxitoxins and domoic acids, okadaiates and azaspiracids, and yessotoxins. Many of these subgroups were recently formed in 2005 and are working towards their goals of producing officially validated analytical methods

  4. Toxins of filamentous fungi.

    Science.gov (United States)

    Bhatnagar, Deepak; Yu, Jiujiang; Ehrlich, Kenneth C

    2002-01-01

    Mycotoxins are low-molecular-weight secondary metabolites of fungi. The most significant mycotoxins are contaminants of agricultural commodities, foods and feeds. Fungi that produce these toxins do so both prior to harvest and during storage. Although contamination of commodities by toxigenic fungi occurs frequently in areas with a hot and humid climate (i.e. conditions favorable for fungal growth), they can also be found in temperate conditions. Production of mycotoxins is dependent upon the type of producing fungus and environmental conditions such as the substrate, water activity (moisture and relative humidity), duration of exposure to stress conditions and microbial, insect or other animal interactions. Although outbreaks of mycotoxicoses in humans have been documented, several of these have not been well characterized, neither has a direct correlation between the mycotoxin and resulting toxic effect been well established in vivo. Even though the specific modes of action of most of the toxins are not well established, acute and chronic effects in prokaryotic and eukaryotic systems, including humans have been reported. The toxicity of the mycotoxins varies considerably with the toxin, the animal species exposed to it, and the extent of exposure, age and nutritional status. Most of the toxic effects of mycotoxins are limited to specific organs, but several mycotoxins affect many organs. Induction of cancer by some mycotoxins is a major concern as a chronic effect of these toxins. It is nearly impossible to eliminate mycotoxins from the foods and feed in spite of the regulatory efforts at the national and international levels to remove the contaminated commodities. This is because mycotoxins are highly stable compounds, the producing fungi are ubiquitous, and food contamination can occur both before and after harvest. Nevertheless, good farm management practices and adequate storage facilities minimize the toxin contamination problems. Current research is

  5. UDP-Glycosyltransferases from the UGT73C Subfamily in Barbarea vulgaris Catalyze Sapogenin 3-O-Glucosylation in Saponin-Mediated Insect Resistance1[W][OA

    Science.gov (United States)

    Augustin, Jörg M.; Drok, Sylvia; Shinoda, Tetsuro; Sanmiya, Kazutsuka; Nielsen, Jens Kvist; Khakimov, Bekzod; Olsen, Carl Erik; Hansen, Esben Halkjær; Kuzina, Vera; Ekstrøm, Claus Thorn; Hauser, Thure; Bak, Søren

    2012-01-01

    Triterpenoid saponins are bioactive metabolites that have evolved recurrently in plants, presumably for defense. Their biosynthesis is poorly understood, as is the relationship between bioactivity and structure. Barbarea vulgaris is the only crucifer known to produce saponins. Hederagenin and oleanolic acid cellobioside make some B. vulgaris plants resistant to important insect pests, while other, susceptible plants produce different saponins. Resistance could be caused by glucosylation of the sapogenins. We identified four family 1 glycosyltransferases (UGTs) that catalyze 3-O-glucosylation of the sapogenins oleanolic acid and hederagenin. Among these, UGT73C10 and UGT73C11 show highest activity, substrate specificity and regiospecificity, and are under positive selection, while UGT73C12 and UGT73C13 show lower substrate specificity and regiospecificity and are under purifying selection. The expression of UGT73C10 and UGT73C11 in different B. vulgaris organs correlates with saponin abundance. Monoglucosylated hederagenin and oleanolic acid were produced in vitro and tested for effects on P. nemorum. 3-O-β-d-Glc hederagenin strongly deterred feeding, while 3-O-β-d-Glc oleanolic acid only had a minor effect, showing that hydroxylation of C23 is important for resistance to this herbivore. The closest homolog in Arabidopsis thaliana, UGT73C5, only showed weak activity toward sapogenins. This indicates that UGT73C10 and UGT73C11 have neofunctionalized to specifically glucosylate sapogenins at the C3 position and demonstrates that C3 monoglucosylation activates resistance. As the UGTs from both the resistant and susceptible types of B. vulgaris glucosylate sapogenins and are not located in the known quantitative trait loci for resistance, the difference between the susceptible and resistant plant types is determined at an earlier stage in saponin biosynthesis. PMID:23027665

  6. Development of an in vivo glucosylation platform by coupling production to growth: Production of phenolic glucosides by a glycosyltransferase of Vitis vinifera.

    Science.gov (United States)

    De Bruyn, Frederik; De Paepe, Brecht; Maertens, Jo; Beauprez, Joeri; De Cocker, Pieter; Mincke, Stein; Stevens, Christian; De Mey, Marjan

    2015-08-01

    Glycosylation of small molecules can significantly alter their properties such as solubility, stability, and/or bioactivity, making glycosides attractive and highly demanded compounds. Consequently, many biotechnological glycosylation approaches have been developed, with enzymatic synthesis and whole-cell biocatalysis as the most prominent techniques. However, most processes still suffer from low yields, production rates and inefficient UDP-sugar formation. To this end, a novel metabolic engineering strategy is presented for the in vivo glucosylation of small molecules in Escherichia coli W. This strategy focuses on the introduction of an alternative sucrose metabolism using sucrose phosphorylase for the direct and efficient generation of glucose 1-phosphate as precursor for UDP-glucose formation and fructose, which serves as a carbon source for growth. By targeted gene deletions, a split metabolism is created whereby glucose 1-phosphate is rerouted from the glycolysis to product formation (i.e., glucosylation). Further, the production pathway was enhanced by increasing and preserving the intracellular UDP-glucose pool. Expression of a versatile glucosyltransferase from Vitis vinifera (VvGT2) enabled the strain to efficiently produce 14 glucose esters of various hydroxycinnamates and hydroxybenzoates with conversion yields up to 100%. To our knowledge, this fast growing (and simultaneously producing) E. coli mutant is the first versatile host described for the glucosylation of phenolic acids in a fermentative way using only sucrose as a cheap and sustainable carbon source. © 2015 Wiley Periodicals, Inc.

  7. Perfringolysin O: The Underrated Clostridium perfringens Toxin?

    Science.gov (United States)

    Verherstraeten, Stefanie; Goossens, Evy; Valgaeren, Bonnie; Pardon, Bart; Timbermont, Leen; Haesebrouck, Freddy; Ducatelle, Richard; Deprez, Piet; Wade, Kristin R; Tweten, Rodney; Van Immerseel, Filip

    2015-05-14

    The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin), a pore-forming cholesterol-dependent cytolysin (CDC). PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol. Membrane-bound monomers undergo structural changes that culminate in the formation of an oligomerized prepore complex on the membrane surface. The prepore then undergoes conversion into the bilayer-spanning pore measuring approximately 250-300 Å in diameter. PFO is expressed in nearly all identified C. perfringens strains and harbors interesting traits that suggest a potential undefined role for PFO in disease development. Research has demonstrated a role for PFO in gas gangrene progression and bovine necrohemorrhagic enteritis, but there is limited data available to determine if PFO also functions in additional disease presentations caused by C. perfringens. This review summarizes the known structural and functional characteristics of PFO, while highlighting recent insights into the potential contributions of PFO to disease pathogenesis.

  8. Perfringolysin O: The Underrated Clostridium perfringens Toxin?

    Directory of Open Access Journals (Sweden)

    Stefanie Verherstraeten

    2015-05-01

    Full Text Available The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin, a pore-forming cholesterol-dependent cytolysin (CDC. PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol. Membrane-bound monomers undergo structural changes that culminate in the formation of an oligomerized prepore complex on the membrane surface. The prepore then undergoes conversion into the bilayer-spanning pore measuring approximately 250–300 Å in diameter. PFO is expressed in nearly all identified C. perfringens strains and harbors interesting traits that suggest a potential undefined role for PFO in disease development. Research has demonstrated a role for PFO in gas gangrene progression and bovine necrohemorrhagic enteritis, but there is limited data available to determine if PFO also functions in additional disease presentations caused by C. perfringens. This review summarizes the known structural and functional characteristics of PFO, while highlighting recent insights into the potential contributions of PFO to disease pathogenesis.

  9. Headache and botulinum toxin

    OpenAIRE

    Porta, M.; Camerlingo, M.

    2005-01-01

    The authors discuss clinical and international experience about botulinum toxins (BTX types A and B) in headache treatment. Data from literature suggest good results for the treatment of tensiontype headache, migraine and chronic tension–type headache. In the present paper mechanisms of action and injection sites will also be discussed.

  10. Botulinum Toxin for Rhinitis.

    Science.gov (United States)

    Ozcan, Cengiz; Ismi, Onur

    2016-08-01

    Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.

  11. Diffusion of Botulinum Toxins

    Directory of Open Access Journals (Sweden)

    Matthew A. Brodsky

    2012-08-01

    Full Text Available Background: It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion.Methods: This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method. It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB.Results: Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others.Discussion: Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected.

  12. Topical Botulinum Toxin

    OpenAIRE

    Collins, Ashley; Nasir, Adnan

    2010-01-01

    Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indicati...

  13. Toxin genotyping of Clostridium perfringens field strains isolated from healthy and diseased chickens

    Directory of Open Access Journals (Sweden)

    Luca Bano

    2010-01-01

    Full Text Available Clostridium perfringens is well known as the aetiological agent of necrotic enteritis in chicken. Type A and type C are considered the C. perfringens toxin types responsible for this disease. The aim of this study was to determine the presence of genes coding for α, β, ε, ι, β2 and enterotoxin in C. perfringens field strains collected from healthy and diseased chickens. Thirty-seven C. perfringens field strains were toxin typed: all strains resulted to be toxin type A and 3 of these tested positive for the presence of the toxin β2 coding gene. Four isolates showed the cpa gene with the insertion of a group II intron. Our findings confirm the most recent results reported from different countries and the data suggest that the role of C. perfringens type C should be revaluated in the etiopathogenesis of necrotic enteritis.

  14. CD44 Promotes intoxication by the clostridial iota-family toxins.

    Science.gov (United States)

    Wigelsworth, Darran J; Ruthel, Gordon; Schnell, Leonie; Herrlich, Peter; Blonder, Josip; Veenstra, Timothy D; Carman, Robert J; Wilkins, Tracy D; Van Nhieu, Guy Tran; Pauillac, Serge; Gibert, Maryse; Sauvonnet, Nathalie; Stiles, Bradley G; Popoff, Michel R; Barth, Holger

    2012-01-01

    Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44(+) melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins.

  15. [Enteral distress syndrome in surgery: definition, pathogenesis, diagnosis].

    Science.gov (United States)

    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.

  16. Toxins and drug discovery.

    Science.gov (United States)

    Harvey, Alan L

    2014-12-15

    Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  17. Sequence variation in the alpha-toxin encoding plc gene of Clostridium perfringens strains isolated from diseased and healthy chickens

    DEFF Research Database (Denmark)

    Abildgaard, L; Engberg, RM; Pedersen, Karl

    2009-01-01

    The aim of the present study was to analyse the genetic diversity of the alpha-toxin encoding plc gene and the variation in a-toxin production of Clostridium perfringens type A strains isolated from presumably healthy chickens and chickens suffering from either necrotic enteritis (NE) or cholangio......-hepatitis. The a-toxin encoding plc genes from 60 different pulsed-field gel electrophoresis (PFGE) types (strains) of C perfringens were sequenced and translated in silico to amino acid sequences and the a-toxin production was investigated in batch cultures of 45 of the strains using an enzyme...

  18. Enteral nutrition - child - managing problems

    Science.gov (United States)

    ... 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 ...

  19. Saccharomyces boulardii Protease Inhibits the Effects of Clostridium difficile Toxins A and B in Human Colonic Mucosa

    Science.gov (United States)

    Castagliuolo, Ignazio; Riegler, Martin F.; Valenick, Leyla; LaMont, J. Thomas; Pothoulakis, Charalabos

    1999-01-01

    Saccharomyces boulardii is a nonpathogenic yeast used in the treatment of Clostridium difficile diarrhea and colitis. We have reported that S. boulardii inhibits C. difficile toxin A enteritis in rats by releasing a 54-kDa protease which digests the toxin A molecule and its brush border membrane (BBM) receptor (I. Castagliuolo, J. T. LaMont, S. T. Nikulasson, and C. Pothoulakis, Infect. Immun. 64:5225–5232, 1996). The aim of this study was to further evaluate the role of S. boulardii protease in preventing C. difficile toxin A enteritis in rat ileum and determine whether it protects human colonic mucosa from C. difficile toxins. A polyclonal rabbit antiserum raised against purified S. boulardii serine protease inhibited by 73% the proteolytic activity present in S. boulardii conditioned medium in vitro. The anti-protease immunoglobulin G (IgG) prevented the action of S. boulardii on toxin A-induced intestinal secretion and mucosal permeability to [3H]mannitol in rat ileal loops, while control rabbit IgG had no effect. The anti-protease IgG also prevented the effects of S. boulardii protease on digestion of toxins A and B and on binding of [3H]toxin A and [3H]toxin B to purified human colonic BBM. Purified S. boulardii protease reversed toxin A- and toxin B-induced inhibition of protein synthesis in human colonic (HT-29) cells. Furthermore, toxin A- and B-induced drops in transepithelial resistance in human colonic mucosa mounted in Ussing chambers were reversed by 60 and 68%, respectively, by preexposing the toxins to S. boulardii protease. We conclude that the protective effects of S. boulardii on C. difficile-induced inflammatory diarrhea in humans are due, at least in part, to proteolytic digestion of toxin A and B molecules by a secreted protease. PMID:9864230

  20. Nanocomposite formation between alpha-glucosyl stevia and surfactant improves the dissolution profile of poorly water-soluble drug.

    Science.gov (United States)

    Uchiyama, Hiromasa; Tozuka, Yuichi; Nishikawa, Masahiro; Takeuchi, Hirofumi

    2012-05-30

    The formation of a hybrid-nanocomposite using α-glucosyl stevia (Stevia-G) and surfactant was explored to improve the dissolution of flurbiprofen (FP). As reported previously, the dissolution amount of FP was enhanced in the presence of Stevia-G, induced by the formation of an FP and Stevia-G-associated nanostructure. When a small amount of sodium dodecyl sulfate (SDS) was present with Stevia-G, the amount of dissolved FP was extremely enhanced. This dissolution-enhancement effect was also observed with the cationic surfactant of dodecyl trimethyl ammonium bromide, but not with the non-ionic surfactant of n-octyl-β-D-maltopyranoside. To investigate the dissolution-enhancement effect of Stevia-G/SDS mixture, the pyrene I(1)/I(3) ratio was plotted versus the Stevia-G concentration. The pyrene I(1)/I(3) ratio of Stevia-G/SDS mixture had a sigmoidal curve at lower Stevia-G concentrations compared to the Stevia-G solution alone. These results indicate that the Stevia-G/SDS mixture provides a hydrophobic core around pyrene molecules at lower Stevia-G concentrations, leading to nanocomposite formation between Stevia-G and SDS. The nanocomposite of Stevia-G/SDS showed no cytotoxicity to Caco-2 cells at a mixture of 0.1% SDS and 1% Stevia-G solution, whereas 0.1% SDS solution showed high toxicity. These results suggest that the nanocomposite formation of Stevia-G/SDS may be useful way to enhance the dissolution of poorly water-soluble drugs without special treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Identification and functional characterization of a flax UDP-glycosyltransferase glucosylating secoisolariciresinol (SECO) into secoisolariciresinol monoglucoside (SMG) and diglucoside (SDG).

    Science.gov (United States)

    Ghose, Kaushik; Selvaraj, Kumarakurubaran; McCallum, Jason; Kirby, Chris W; Sweeney-Nixon, Marva; Cloutier, Sylvie J; Deyholos, Michael; Datla, Raju; Fofana, Bourlaye

    2014-03-28

    Lignans are a class of diphenolic nonsteroidal phytoestrogens often found glycosylated in planta. Flax seeds are a rich source of secoisolariciresinol diglucoside (SDG) lignans. Glycosylation is a process by which a glycosyl group is covalently attached to an aglycone substrate and is catalyzed by uridine diphosphate glycosyltransferases (UGTs). Until now, very little information was available on UGT genes that may play a role in flax SDG biosynthesis. Here we report on the identification, structural and functional characterization of 5 putative UGTs potentially involved in secoisolariciresinol (SECO) glucosylation in flax. Five UGT genes belonging to the glycosyltransferases' family 1 (EC 2.4.x.y) were cloned and characterized. They fall under four UGT families corresponding to five sub-families referred to as UGT74S1, UGT74T1, UGT89B3, UGT94H1, UGT712B1 that all display the characteristic plant secondary product glycosyltransferase (PSPG) conserved motif. However, diversity was observed within this 44 amino acid sequence, especially in the two peptide sequences WAPQV and HCGWNS known to play a key role in the recognition and binding of diverse aglycone substrates and in the sugar donor specificity. In developing flax seeds, UGT74S1 and UGT94H1 showed a coordinated gene expression with that of pinoresinol-lariciresinol reductase (PLR) and their gene expression patterns correlated with SDG biosynthesis. Enzyme assays of the five heterologously expressed UGTs identified UGT74S1 as the only one using SECO as substrate, forming SECO monoglucoside (SMG) and then SDG in a sequential manner. We have cloned and characterized five flax UGTs and provided evidence that UGT74S1 uses SECO as substrate to form SDG in vitro. This study allowed us to propose a model for the missing step in SDG lignan biosynthesis.

  2. Mechanisms of Action and Cell Death Associated with Clostridium perfringens Toxins

    Directory of Open Access Journals (Sweden)

    Mauricio A. Navarro

    2018-05-01

    Full Text Available Clostridium perfringens uses its large arsenal of protein toxins to produce histotoxic, neurologic and intestinal infections in humans and animals. The major toxins involved in diseases are alpha (CPA, beta (CPB, epsilon (ETX, iota (ITX, enterotoxin (CPE, and necrotic B-like (NetB toxins. CPA is the main virulence factor involved in gas gangrene in humans, whereas its role in animal diseases is limited and controversial. CPB is responsible for necrotizing enteritis and enterotoxemia, mostly in neonatal individuals of many animal species, including humans. ETX is the main toxin involved in enterotoxemia of sheep and goats. ITX has been implicated in cases of enteritis in rabbits and other animal species; however, its specific role in causing disease has not been proved. CPE is responsible for human food-poisoning and non-foodborne C. perfringens-mediated diarrhea. NetB is the cause of necrotic enteritis in chickens. In most cases, host–toxin interaction starts on the plasma membrane of target cells via specific receptors, resulting in the activation of intracellular pathways with a variety of effects, commonly including cell death. In general, the molecular mechanisms of cell death associated with C. perfringens toxins involve features of apoptosis, necrosis and/or necroptosis.

  3. The toxins of Cyanobacteria.

    Science.gov (United States)

    Patocka, J

    2001-01-01

    Cyanobacteria, formerly called "blue-green algae", are simple, primitive photosynthetic microorganism wide occurrence in fresh, brackish and salt waters. Forty different genera of Cyanobacteria are known and many of them are producers of potent toxins responsible for a wide array of human illnesses, aquatic mammal and bird morbidity and mortality, and extensive fish kills. These cyanotoxins act as neurotoxins or hepatotoxins and are structurally and functionally diverse, and many are derived from unique biosynthetic pathways. All known cyanotoxins and their chemical and toxicological characteristics are presented in this article.

  4. [Modular enteral nutrition in pediatrics].

    Science.gov (United States)

    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.

  5. Microscopic enteritis: Bucharest consensus.

    Science.gov (United States)

    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.

  6. Clostridial necrotic enteritis in chicken associated with growth rate depression

    Directory of Open Access Journals (Sweden)

    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.

  7. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  8. Botulinum toxin: bioweapon & magic drug.

    Science.gov (United States)

    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-11-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

  9. Toxin-Based Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Itai Benhar

    2010-10-01

    Full Text Available Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

  10. Toxin-Based Therapeutic Approaches

    Science.gov (United States)

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  11. Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation.

    Science.gov (United States)

    Jesus, Ana R; Vila-Viçosa, Diogo; Machuqueiro, Miguel; Marques, Ana P; Dore, Timothy M; Rauter, Amélia P

    2017-01-26

    Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC 50 = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC 50 = 10-19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a C-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2.

  12. A Novel Glucosylation Reaction on Anthocyanins Catalyzed by Acyl-Glucose–Dependent Glucosyltransferase in the Petals of Carnation and Delphinium[C][W

    Science.gov (United States)

    Matsuba, Yuki; Sasaki, Nobuhiro; Tera, Masayuki; Okamura, Masachika; Abe, Yutaka; Okamoto, Emi; Nakamura, Haruka; Funabashi, Hisakage; Takatsu, Makoto; Saito, Mikako; Matsuoka, Hideaki; Nagasawa, Kazuo; Ozeki, Yoshihiro

    2010-01-01

    Glucosylation of anthocyanin in carnations (Dianthus caryophyllus) and delphiniums (Delphinium grandiflorum) involves novel sugar donors, aromatic acyl-glucoses, in a reaction catalyzed by the enzymes acyl-glucose–dependent anthocyanin 5(7)-O-glucosyltransferase (AA5GT and AA7GT). The AA5GT enzyme was purified from carnation petals, and cDNAs encoding carnation Dc AA5GT and the delphinium homolog Dg AA7GT were isolated. Recombinant Dc AA5GT and Dg AA7GT proteins showed AA5GT and AA7GT activities in vitro. Although expression of Dc AA5GT in developing carnation petals was highest at early stages, AA5GT activity and anthocyanin accumulation continued to increase during later stages. Neither Dc AA5GT expression nor AA5GT activity was observed in the petals of mutant carnations; these petals accumulated anthocyanin lacking the glucosyl moiety at the 5 position. Transient expression of Dc AA5GT in petal cells of mutant carnations is expected to result in the transfer of a glucose moiety to the 5 position of anthocyanin. The amino acid sequences of Dc AA5GT and Dg AA7GT showed high similarity to glycoside hydrolase family 1 proteins, which typically act as β-glycosidases. A phylogenetic analysis of the amino acid sequences suggested that other plant species are likely to have similar acyl-glucose–dependent glucosyltransferases. PMID:20971893

  13. Specific tritium labelling of glucosyl- and galactosylceramides at the 6-position of the carbohydrate moiety using CrO3-graphite

    International Nuclear Information System (INIS)

    Usuki, S.; Nagai, Y.

    1986-01-01

    A new procedure for introducing tritium into the carbohydrate portions of glucosyl- and galactosylceramides was developed using a new catalyst, CrO3-graphite, which specifically oxidizes the primary alcohol group to the aldehyde. About 10% of the glycolipid was converted to the aldehyde and the aldehyde produced was then reduced back to the original form with KB3H4. After methanolysis, more than 96.7% of the radioactivities of [3H]glucosyl- and [3H]galactosylceramides were found to be located in the carbohydrate portions, and the specific activities of the [3H]galactosyl- and [3H]glucosylceramides were 2.08 to 4.30 X 10(4) cpm/nmol, which could be increased greatly by purifying the aldehydes and reducing them with KB3H4. In addition, beta-galactosidase activity was successfully determined with [3H]galactosylceramide as the enzyme substrate; the Km was 18.73 mM and the Vmax was 11.63 nmol/mg/h, indicating that no significant structural modification occurs during the oxidation

  14. Binding of ATP by pertussis toxin and isolated toxin subunits

    International Nuclear Information System (INIS)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L.

    1990-01-01

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of [ 3 H]ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of [ 3 H]ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of [ 3 H]ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site

  15. Binding of ATP by pertussis toxin and isolated toxin subunits

    Energy Technology Data Exchange (ETDEWEB)

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L. (Center for Biologics Evaluation and Research, Bethesda, MD (USA))

    1990-07-03

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.

  16. Enteral feeding without pancreatic stimulation

    DEFF Research Database (Denmark)

    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...

  17. Food toxin detection with atomic force microscope

    Science.gov (United States)

    Externally introduced toxins or internal spoilage correlated pathogens and their metabolites are all potential sources of food toxins. To prevent and protect unsafe food, many food toxin detection techniques have been developed to detect various toxins for quality control. Although several routine m...

  18. Botulinum Toxin (Botox) for Facial Wrinkles

    Science.gov (United States)

    ... Stories Español Eye Health / Eye Health A-Z Botulinum Toxin (Botox) for Facial Wrinkles Sections Botulinum Toxin (Botox) ... Facial Wrinkles How Does Botulinum Toxin (Botox) Work? Botulinum Toxin (Botox) for Facial Wrinkles Leer en Español: La ...

  19. Bio Warfare and Terrorism: Toxins and Other Mid-Spectrum Agents

    National Research Council Canada - National Science Library

    Madsen, James M

    2005-01-01

    ... counterparts are still by definition toxins. Related terms include phycotoxins (toxins from algae), mycotoxins (fungal toxins), phytotoxins (plant toxins), and venoms (toxins from animals, especially vertebrates...

  20. Combined enteral and parenteral nutrition.

    Science.gov (United States)

    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.

  1. Yeast Killer Toxin K28: Biology and Unique Strategy of Host Cell Intoxication and Killing

    Directory of Open Access Journals (Sweden)

    Björn Becker

    2017-10-01

    Full Text Available The initial discovery of killer toxin-secreting brewery strains of Saccharomyces cerevisiae (S. cerevisiae in the mid-sixties of the last century marked the beginning of intensive research in the yeast virology field. So far, four different S. cerevisiae killer toxins (K28, K1, K2, and Klus, encoded by cytoplasmic inherited double-stranded RNA viruses (dsRNA of the Totiviridae family, have been identified. Among these, K28 represents the unique example of a yeast viral killer toxin that enters a sensitive cell by receptor-mediated endocytosis to reach its intracellular target(s. This review summarizes and discusses the most recent advances and current knowledge on yeast killer toxin K28, with special emphasis on its endocytosis and intracellular trafficking, pointing towards future directions and open questions in this still timely and fascinating field of killer yeast research.

  2. Botulinum toxin in trigeminal neuralgia.

    Science.gov (United States)

    Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia

    2017-01-06

    Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Toxin-Based Therapeutic Approaches

    OpenAIRE

    Itai Benhar; Assaf Shapira

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmac...

  4. Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin.

    Science.gov (United States)

    Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko

    2018-05-20

    Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca 2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca 2+ . Ib induced the extracellular release of ASMase in the presence of Ca 2+ . ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells.

  5. Enteric Methane Emission from Pigs

    DEFF Research Database (Denmark)

    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

    Directory of Open Access Journals (Sweden)

    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. Histidine 352 (His352 and tryptophan 355 (Trp355 are essential for flax UGT74S1 glucosylation activity toward secoisolariciresinol.

    Directory of Open Access Journals (Sweden)

    Kaushik Ghose

    Full Text Available Flax secoisolariciresinol diglucoside (SDG lignan is a natural phytoestrogen for which a positive role in metabolic diseases is emerging. Until recently however, much less was known about SDG and its monoglucoside (SMG biosynthesis. Lately, flax UGT74S1 was identified and characterized as an enzyme sequentially glucosylating secoisolariciresinol (SECO into SMG and SDG when expressed in yeast. However, the amino acids critical for UGT74S1 glucosyltransferase activity were unknown. A 3D structural modeling and docking, site-directed mutagenesis of five amino acids in the plant secondary product glycosyltransferase (PSPG motif, and enzyme assays were conducted. UGT74S1 appeared to be structurally similar to the Arabidopsis thaliana UGT72B1 model. The ligand docking predicted Ser357 and Trp355 as binding to the phosphate and hydroxyl groups of UDP-glucose, whereas Cys335, Gln337 and Trp355 were predicted to bind the 7-OH, 2-OCH3 and 17-OCH3 of SECO. Site-directed mutagenesis of Cys335, Gln337, His352, Trp355 and Ser357, and enzyme assays revealed an alteration of these binding sites and a significant reduction of UGT74S1 glucosyltransferase catalytic activity towards SECO and UDP-glucose in all mutants. A complete abolition of UGT74S1 activity was observed when Trp355 was substituted to Ala355 and Gly355 or when changing His352 to Asp352, and an altered metabolite profile was observed in Cys335Ala, Gln337Ala, and Ser357Ala mutants. This study provided for the first time evidence that Trp355 and His352 are critical for UGT74S1's glucosylation activity toward SECO and suggested the possibility for SMG production in vitro.

  8. The enter-educate approach.

    Science.gov (United States)

    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.

  9. Meat-based enteral nutrition

    Science.gov (United States)

    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.

  10. Botulinum toxin in pain treatment.

    Science.gov (United States)

    Colhado, Orlando Carlos Gomes; Boeing, Marcelo; Ortega, Luciano Bornia

    2009-01-01

    Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known. However, the efficacy of some of its indications is still in the process of being confirmed. The objective of this study was to review the history, pharmacological properties, and clinical applications of BTX in the treatment of pain of different origins. Botulinum toxin is produced by fermentation of Clostridium botulinum, a Gram-positive, anaerobic bacterium. Commercially, BTX comes in two presentations, types A and B. Botulinum toxin, a neurotoxin with high affinity for cholinergic synapses, blocks the release of acetylcholine by nerve endings without interfering with neuronal conduction of electrical signals or synthesis and storage of acetylcholine. It has been proven that BTX can selectively weaken painful muscles, interrupting the spasm-pain cycle. Several studies have demonstrated the efficacy and safety of BTX-A in the treatment of tension headaches, migraines, chronic lumbar pain, and myofascial pain. Botulinum toxin type A is well tolerated in the treatment of chronic pain disorders in which pharmacotherapy regimens can cause side effects. The reduction in the consumption of analgesics and length of action of 3 to 4 months per dose represent other advantages of its use. However, further studies are necessary to establish the efficacy of BTX-A in chronic pain disorders and its exact mechanism of action, as well as its potential in multifactorial treatments.

  11. Occurrence of Beta2 toxigenic Clostridium perfringens isolates with different toxin types in Iran

    Directory of Open Access Journals (Sweden)

    Jabbari, A.R.

    2012-11-01

    Full Text Available Clostridium perfringens is an important cause of enteric diseases in both human and animals. The bacteria produce several toxins which play key roles in the pathogenesis of diseases and are classified into five toxin types, on the basis of the differential production of Alpha, Beta, Epsilon and Iota toxins. In this study a single PCR assay was developed and used for detection of cpb2 gene to identify the Beta2 harboring isolates among different types of C. perfringens isolated from animal enteric diseases in Iran. It was found that cpb2 presents among C. perfringens isolates types A, B, C and D with 54.5% (6/11, 62% (13/21, 42.8% (6/14, 69.25% (9/13, respectively. Totally 34 of 59 (56.7% isolates screened by PCR were cpb2-positive. This is the first report of cpb2 positive isolates of C. perfringens causing enteric diseases of animals in Iran. Further studies to demonstrate the exact role of Beta2 toxin in pathogenesis of the bacterium is suggested.

  12. Entry of Shiga toxin into cells

    DEFF Research Database (Denmark)

    Sandvig, Kirsten; van Deurs, Bo

    1994-01-01

    Cellebiologi, Shiga toxin, receptors, glycolipids, endocytosis, trans-Golgi network, endoplasmic reticulum, retrograde transport......Cellebiologi, Shiga toxin, receptors, glycolipids, endocytosis, trans-Golgi network, endoplasmic reticulum, retrograde transport...

  13. Inhibition of cholera toxin and other AB toxins by polyphenolic compounds

    Science.gov (United States)

    All AB-type protein toxins have intracellular targets despite an initial extracellular location. These toxins use different methods to reach the cytosol and have different effects on the target cell. Broad-spectrum inhibitors against AB toxins are therefore hard to develop because the toxins use dif...

  14. Toxin synergism in snake venoms

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard

    2016-01-01

    Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components, and can be the result of toxins targeting the same protein, biochemical pathway or physiological process. Few...... simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel...

  15. Nutrición enteral

    OpenAIRE

    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.

  16. [Enteral nutrition in burn patients].

    Science.gov (United States)

    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

  17. Glucose, epithelium, and enteric nervous system: dialogue in the dark.

    Science.gov (United States)

    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.

  18. Lipid reorganization induced by Shiga toxin clustering on planar membranes.

    Directory of Open Access Journals (Sweden)

    Barbara Windschiegl

    Full Text Available The homopentameric B-subunit of bacterial protein Shiga toxin (STxB binds to the glycolipid Gb(3 in plasma membranes, which is the initial step for entering cells by a clathrin-independent mechanism. It has been suggested that protein clustering and lipid reorganization determine toxin uptake into cells. Here, we elucidated the molecular requirements for STxB induced Gb(3 clustering and for the proposed lipid reorganization in planar membranes. The influence of binding site III of the B-subunit as well as the Gb(3 lipid structure was investigated by means of high resolution methods such as fluorescence and scanning force microscopy. STxB was found to form protein clusters on homogenous 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC/cholesterol/Gb(3 (65:30:5 bilayers. In contrast, membranes composed of DOPC/cholesterol/sphingomyelin/Gb(3 (40:35:20:5 phase separate into a liquid ordered and liquid disordered phase. Dependent on the fatty acid composition of Gb(3, STxB-Gb(3 complexes organize within the liquid ordered phase upon protein binding. Our findings suggest that STxB is capable of forming a new membrane phase that is characterized by lipid compaction. The significance of this finding is discussed in the context of Shiga toxin-induced formation of endocytic membrane invaginations.

  19. [Environmental toxins in breast milk].

    Science.gov (United States)

    Bratlid, Dag

    2009-12-17

    Breast milk is very important to ensure infants a well-composed and safe diet during the first year of life. However, the quality of breast milk seems to be affected by an increasing amount of environmental toxins (particularly so-called Persistent, Bioaccumulative Toxins [PBTs]). Many concerns have been raised about the negative effects this may have on infant health. The article is a review of literature (mainly review articles) identified through a non-systematic search in PubMed. The concentration of PBTs in breast milk is mainly caused by man's position as the terminal link in the nutritional chain. Many breast-fed infants have a daily intake of such toxins that exceed limits defined for the population in general. Animal studies demonstrate effects on endocrine function and neurotoxicity in the offspring, and a number of human studies seem to point in the same direction. However the "original" optimal composition of breast milk still seems to protect against long-term effects of such toxicity. There is international consensus about the need to monitor breast milk for the presence of PBTs. Such surveillance will be a good indicator of the population's general exposure to these toxins and may also contribute to identifying groups as risk who should not breast-feed their children for a long time.

  20. Risk Assessment of Shellfish Toxins

    Directory of Open Access Journals (Sweden)

    Rex Munday

    2013-11-01

    Full Text Available Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the tissues of the predators, which then become toxic to animals higher up the food chain. This is a particular problem with shellfish, and many cases of poisoning are reported in shellfish consumers each year. At present, there is no practicable means of preventing uptake of the toxins by shellfish or of removing them after harvesting. Assessment of the risk posed by such toxins is therefore required in order to determine levels that are unlikely to cause adverse effects in humans and to permit the establishment of regulatory limits in shellfish for human consumption. In the present review, the basic principles of risk assessment are described, and the progress made toward robust risk assessment of seafood toxins is discussed. While good progress has been made, it is clear that further toxicological studies are required before this goal is fully achieved.

  1. Food irradiation and bacterial toxins

    International Nuclear Information System (INIS)

    Tranter, H.S.; Modi, N.K.; Hambleton, P.; Melling, J.; Rose, S.; Stringer, M.F.

    1987-01-01

    The authors' findings indicate that irradiation confers no advantage over heat processing in respect of bacterial toxins (clostridium botulinum, neurotoxin A and staphylococcal enterotoxin A). It follows that irradiation at doses less than the ACINF recommended upper limit of 10 kGy could not be used to improve the ambient temperature shelf life on non-acid foods. (author)

  2. Botulinum toxin for vaginismus treatment.

    Science.gov (United States)

    Ferreira, Juliana Rocha; Souza, Renan Pedra

    2012-01-01

    Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when penile, finger, tampon, or speculum penetration is attempted. Recent results have suggested the use of botulinum toxin for the treatment of vaginismus. Here, we assessed previously published data to evaluate the therapeutic effectiveness of botulinum toxin for vaginismus. We have carried out a systematic review followed by a meta-analysis. Our results indicate that botulinum toxin is an effective therapeutic option for patients with vaginismus (pooled odds ratio of 8.723 with 95% confidence interval limits of 1.942 and 39.162, p = 0.005). This may hold particularly true in treatment-refractory patients because most of the studies included in this meta-analysis have enrolled these subjects in their primary analysis. Botulinum toxin appears to bea reasonable intervention for vaginismus. However, this conclusion should be read carefully because of the deficiency of placebo-controlled randomized clinical trials and the quality issues presented in the existing ones.

  3. Shigella Sonnei and Shiga Toxin

    Centers for Disease Control (CDC) Podcasts

    2016-07-28

    Katherine Lamba, an infectious disease epidemiologist with the California Department of Public Health, discusses Shiga Toxin producing Shigella sonnei.  Created: 7/28/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/28/2016.

  4. CERN openlab enters fifth phase

    CERN Multimedia

    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...

  5. Surgical treatment of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Surgical treatment of radiation enteritis

    International Nuclear Information System (INIS)

    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

  7. Biosynthetic elongation of isolated teichuronic acid polymers via glucosyl- and N-acetylmannosaminuronosyltransferases from solubilized cytoplasmic membrane fragments of Micrococcus luteus.

    Science.gov (United States)

    Hildebrandt, K M; Anderson, J S

    1990-01-01

    Cytoplasmic membrane fragments of Micrococcus luteus catalyze in vitro biosynthesis of teichuronic acid from uridine diphosphate D-glucose (UDP-glucose), uridine diphosphate N-acetyl-D-mannosaminuronic acid (UDP-ManNAcA), and uridine diphosphate N-acetyl-D-glucosamine. Membrane fragments solubilized with Thesit (dodecyl alcohol polyoxyethylene ether) can utilize UDP-glucose and UDP-ManNAcA to effect elongation of teichuronic acid isolated from native cell walls. When UDP-glucose is the only substrate supplied, the detergent-solubilized glucosyltransferase incorporates a single glucosyl residue onto each teichuronic acid acceptor. When both UDP-glucose and UDP-ManNAcA are supplied, the glucosyltransferase and the N-acetylmannosaminuronosyltransferase act cooperatively to elongate the teichuronic acid acceptor by multiple additions of the disaccharide repeat unit. As shown by polyacrylamide gel electrophoresis, low-molecular-weight fractions of teichuronic acid are converted to higher-molecular-weight polymers by the addition of as many as 17 disaccharide repeat units. Images PMID:2118507

  8. Hybridization of polyvinylpyrrolidone to a binary composite of curcumin/α-glucosyl stevia improves both oral absorption and photochemical stability of curcumin.

    Science.gov (United States)

    Kadota, Kazunori; Okamoto, Daiki; Sato, Hideyuki; Onoue, Satomi; Otsu, Shigeyuki; Tozuka, Yuichi

    2016-12-15

    The tri-component system curcumin/α-glucosyl stevia (Stevia-G)/polyvinylpyrrolidone (PVP) was developed to improve the oral bioavailability and physicochemical properties of curcumin (CUR). The tri-component CUR formulation with Stevia-G and PVP was prepared with freeze-drying. The tri-component CUR system exhibited 13,000-fold higher solubility of CUR than the equilibrium solubility of CUR for 24h, indicating a stable tri-composite structure involving CUR. CUR could be converted into an amorphous form in the presence of Stevia-G and PVP by freeze-drying. The photo-degradation of CUR in the tri-component system was negligible even under an amorphous state of CUR. After oral administration in rats, the oral absorption of the tri-component CUR formulation (20mgCUR/kg) was 6.7-fold higher than that of crystalline CUR. The tri-component CUR formulation would therefore be a promising option to improve physicochemical properties and oral absorption of CUR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Why do we study animal toxins?

    Science.gov (United States)

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  10. Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay

    OpenAIRE

    Lewis, Richard J.; Inserra, Marco; Vetter, Irina; Holland, William C.; Hardison, D. Ransom; Tester, Patricia A.; Litaker, R. Wayne

    2016-01-01

    Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins. Methods We established a simplified proce...

  11. Cyanobacteria toxins in the Salton Sea.

    Science.gov (United States)

    Carmichael, Wayne W; Li, RenHui

    2006-04-19

    The Salton Sea (SS) is the largest inland body of water in California: surface area 980 km2, volume 7.3 million acre-feet, 58 km long, 14-22 km wide, maximum depth 15 m. Located in the southeastern Sonoran desert of California, it is 85 m below sea level at its lowest point. It was formed between 1905 and 1907 from heavy river flows of the Colorado River. Since its formation, it has attracted both people and wildlife, including flocks of migratory birds that have made the Salton Sea a critical stopover on the Pacific flyway. Over the past 15 years wintering populations of eared grebe (Podiceps nigricollis) at the Salton Sea, have experienced over 200,000 mortalities. The cause of these large die-offs remains unknown. The unique environmental conditions of the Salton Sea, including salinities from brackish freshwater at river inlets to hypersaline conditions, extreme daily summer temperatures (>38 degrees C), and high nutrient loading from rivers and agricultural drainage favor eutrophic conditions that encourage algal blooms throughout the year. A significant component of these algal blooms are the prokaryotic group - the Cyanophyta or blue-green algae (also called Cyanobacteria). Since many Cyanobacteria produce toxins (the cyanotoxins) it became important to evaluate their presence and to determine if they are a contributing factor in eared-grebe mortalities at the Salton Sea. From November 1999 to April 2001, 247 water and sediment samples were received for phytoplankton identification and cyanotoxin analyses. Immunoassay (ELISA) screening of these samples found that eighty five percent of all water samples contained low but detectable levels of the potent cyclic peptide liver toxin called microcystins. Isolation and identification of cyanobacteria isolates showed that the picoplanktonic Synechococcus and the benthic filamentous Oscillatoria were dominant. Both organisms were found to produce microcystins dominated by microcystin-LR and YR. A laboratory strain

  12. Enteral Feeding Set Handling Techniques.

    Science.gov (United States)

    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.

  13. The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-induced necrotic enteritis in broiler chickens.

    Science.gov (United States)

    Antonissen, Gunther; Van Immerseel, Filip; Pasmans, Frank; Ducatelle, Richard; Haesebrouck, Freddy; Timbermont, Leen; Verlinden, Marc; Janssens, Geert Paul Jules; Eeckhaut, Venessa; Eeckhout, Mia; De Saeger, Sarah; Hessenberger, Sabine; Martel, An; Croubels, Siska

    2014-01-01

    Both mycotoxin contamination of feed and Clostridium perfringens-induced necrotic enteritis have an increasing global economic impact on poultry production. Especially the Fusarium mycotoxin deoxynivalenol (DON) is a common feed contaminant. This study aimed at examining the predisposing effect of DON on the development of necrotic enteritis in broiler chickens. An experimental Clostridium perfringens infection study revealed that DON, at a contamination level of 3,000 to 4,000 µg/kg feed, increased the percentage of birds with subclinical necrotic enteritis from 20±2.6% to 47±3.0% (Peffect on in vitro growth, alpha toxin production and netB toxin transcription of Clostridium perfringens. In conclusion, feed contamination with DON at concentrations below the European maximum guidance level of 5,000 µg/kg feed, is a predisposing factor for the development of necrotic enteritis in broilers. These results are associated with a negative effect of DON on the intestinal barrier function and increased intestinal protein availability, which may stimulate growth and toxin production of Clostridium perfringens.

  14. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

    Directory of Open Access Journals (Sweden)

    Hendrik Fuchs

    2016-07-01

    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  15. Computational Studies of Snake Venom Toxins

    OpenAIRE

    Paola G. Ojeda; David Ramírez; Jans Alzate-Morales; Julio Caballero; Quentin Kaas; Wendy González

    2017-01-01

    Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics t...

  16. Collaborative Research Program on Seafood Toxins

    Science.gov (United States)

    1988-08-14

    Crystallographic Structures of Saxitoxins Cl and C2 Appendix C: Collaborative Research Program an Seafcod Toxins Progress Report on Ciguatera and Related...radioimmunoassay for PSP were also evalumted. The Hokama stick test for ciguatera toxin was also evaluated. 4. initiate Studies on the Accumulation...tco•d which caie a form of b-mnn poisoning referred to as ciguatera . The respcnsible toxins originate from ll1ular rine algae of the division

  17. A Map Enters the Conversation

    DEFF Research Database (Denmark)

    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...

  18. Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

    Science.gov (United States)

    Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

    2015-12-01

    To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

  19. Advantages of enteral nutrition over parenteral nutrition

    OpenAIRE

    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.

  20. Botulinum toxin in bruxism treatment

    Directory of Open Access Journals (Sweden)

    Piotr Piech

    2017-07-01

    Full Text Available Introduction: Bruxism is defined as abnormal, fixed, unconscious chewing organ function, deviating qualitatively and quantitatively from normal function. Another definition speaks of motor dysfunction in the mouth, characterized by grinding and clenching of the teeth, occurring during sleep. The etiology of this disorder has not been explained until now, but it is believed to be related to localized, mental, nervous and neurotransmitter disorders. Purpose: The aim of the study is to review literature and knowledge about the use of botulinum toxin in the treatment of bruxism. Methods of treatment: The patient reports to the physician usually after a distressing, difficult to locate pain. The basis for proper treatment is to detect parafunctions and to make the patient aware of their existence. Diagnostic symptoms include dentinal lesions, recesses, enamel cracks and abfractive cavities, as well as changes in the mucosal area of the cheeks. Treatment begins with the use of an occlusive therapy to relax muscles, reduce parafunction and relieve pain. In the form of severe pain, NSAIDs are introduced and, if necessary, anxiolytics, sedatives and antidepressants. In the absence of response to the treatment used, botulinum toxin type A injections are used. The dose of the agent depends on the initial muscle tone and the effect of decrease in its activity is maintained for 4 to 6 months. Conclusions: The use of botulinum toxin makes it possible to selectively exclude overactive muscles, which is a great advantage over other techniques. An additional benefit of this therapy is achieved good cosmetic effect, reversible effect and minimal amount of side effects.

  1. Botulinum toxin: The Midas touch.

    Science.gov (United States)

    Shilpa, P S; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

    2014-01-01

    Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases.

  2. Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins.

    Science.gov (United States)

    Stivala, Craig E; Benoit, Evelyne; Aráoz, Rómulo; Servent, Denis; Novikov, Alexei; Molgó, Jordi; Zakarian, Armen

    2015-03-01

    From a small group of exotic compounds isolated only two decades ago, Cyclic Imine (CI) toxins have become a major class of marine toxins with global distribution. Their distinct chemical structure, biological mechanism of action, and intricate chemistry ensures that CI toxins will continue to be the subject of fascinating fundamental studies in the broad fields of chemistry, chemical biology, and toxicology. The worldwide occurrence of potent CI toxins in marine environments, their accumulation in shellfish, and chemical stability are important considerations in assessing risk factors for human health. This review article aims to provide an account of chemistry, biology, and toxicology of CI toxins from their discovery to the present day.

  3. A Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin

    National Research Council Canada - National Science Library

    Merrill, Gerald A; Rivera, Victor R; Neal, Dwayne D; Young, Charles; Poli, Mark A

    2006-01-01

    .... Biotinylated antibodies to C. perfringens alpha toxin bound to streptavidin paramagnetic beads specifically immunoadsorbed soluble sample alpha toxin which subsequently selectively immunoadsorbed ruthenium (Ru...

  4. Synergistic effect of embryo vaccination with Eimeria profilin and Clostridium perfringens NetB proteins on inducing protective immunity against necrotic enteritis in broiler chickens

    Science.gov (United States)

    The effects of embryo vaccination with Eimeria profilin plus Clostridium perfringens NetB toxin proteins in combination with the Montanide IMS-OVO adjuvant on the chicken immune response to necrotic enteritis were investigated using an E. maxima/C. perfringens co-infection model. Eighteen-day-old br...

  5. Toxin-Antitoxin Battle in Bacteria

    DEFF Research Database (Denmark)

    Cataudella, Ilaria

    This PhD thesis consists of three research projects revolving around the common thread of investigation of the properties and biological functions of Toxin-Antitoxin loci. Toxin-Antitoxin (TA) loci are transcriptionally regulated via an auto-inhibition mechanism called conditional cooperativity, ...

  6. Plant insecticidal toxins in ecological networks.

    Science.gov (United States)

    Ibanez, Sébastien; Gallet, Christiane; Després, Laurence

    2012-04-01

    Plant secondary metabolites play a key role in plant-insect interactions, whether constitutive or induced, C- or N-based. Anti-herbivore defences against insects can act as repellents, deterrents, growth inhibitors or cause direct mortality. In turn, insects have evolved a variety of strategies to act against plant toxins, e.g., avoidance, excretion, sequestration and degradation of the toxin, eventually leading to a co-evolutionary arms race between insects and plants and to co-diversification. Anti-herbivore defences also negatively impact mutualistic partners, possibly leading to an ecological cost of toxin production. However, in other cases toxins can also be used by plants involved in mutualistic interactions to exclude inadequate partners and to modify the cost/benefit ratio of mutualism to their advantage. When considering the whole community, toxins have an effect at many trophic levels. Aposematic insects sequester toxins to defend themselves against predators. Depending on the ecological context, toxins can either increase insects' vulnerability to parasitoids and entomopathogens or protect them, eventually leading to self-medication. We conclude that studying the community-level impacts of plant toxins can provide new insights into the synthesis between community and evolutionary ecology.

  7. Plant Insecticidal Toxins in Ecological Networks

    Directory of Open Access Journals (Sweden)

    Sébastien Ibanez

    2012-04-01

    Full Text Available Plant secondary metabolites play a key role in plant-insect interactions, whether constitutive or induced, C- or N-based. Anti-herbivore defences against insects can act as repellents, deterrents, growth inhibitors or cause direct mortality. In turn, insects have evolved a variety of strategies to act against plant toxins, e.g., avoidance, excretion, sequestration and degradation of the toxin, eventually leading to a co-evolutionary arms race between insects and plants and to co-diversification. Anti-herbivore defences also negatively impact mutualistic partners, possibly leading to an ecological cost of toxin production. However, in other cases toxins can also be used by plants involved in mutualistic interactions to exclude inadequate partners and to modify the cost/benefit ratio of mutualism to their advantage. When considering the whole community, toxins have an effect at many trophic levels. Aposematic insects sequester toxins to defend themselves against predators. Depending on the ecological context, toxins can either increase insects’ vulnerability to parasitoids and entomopathogens or protect them, eventually leading to self-medication. We conclude that studying the community-level impacts of plant toxins can provide new insights into the synthesis between community and evolutionary ecology.

  8. Stealth and mimicry by deadly bacterial toxins

    DEFF Research Database (Denmark)

    Yates, S.P.; Jørgensen, Rene; Andersen, Gregers Rom

    2006-01-01

    Diphtheria toxin and exotoxin A are well-characterized members of the ADP-ribosyltransferase toxin family that serve as virulence factors in the pathogenic bacteria, Corynebacterium diphtheriae and Pseudomonas aeruginosa.  New high-resolution structural data of the Michaelis complex...

  9. Enteric-coated mycophenolate sodium.

    Science.gov (United States)

    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.

  10. CERN openlab enters new phase

    CERN Multimedia

    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 ...

  11. Clostridium difficile toxin B inhibits the secretory response of human mast cell line-1 (HMC-1) cells stimulated with high free-Ca2+ and GTPγS

    International Nuclear Information System (INIS)

    Balletta, Andrea; Lorenz, Dorothea; Rummel, Andreas; Gerhard, Ralf; Bigalke, Hans; Wegner, Florian

    2015-01-01

    Clostridium difficile toxins A and B (TcdA and TcdB) belong to the class of large clostridial cytotoxins and inactivate by glucosylation some low molecular mass GTPases of the Rho-family (predominantly Rho, Rac and Cdc42), known as regulators of the actin cytoskeleton. TcdA and B also represent the main virulence factors of the anaerobic gram-positive bacterium that is the causal agent of pseudomembranous colitis. In our study, TcdB was chosen instead of TcdA for the well-known higher cytotoxic potency. Inactivation of Rho-family GTPases by this toxin in our experimental conditions induced morphological changes and reduction of electron-dense mast cell-specific granules in human mast cell line-1 (HMC-1) cells, but not cell death or permeabilisation of plasma-membranes. Previously reported patch-clamp dialysis experiments revealed that high intracellular free-Ca 2+ and GTPγS concentrations are capable of inducing exocytosis as indicated by significant membrane capacitance (C m ) increases in HMC-1 cells. In this study, we investigated the direct effects of TcdB upon HMC-1 cell “stimulated” C m increase, as well as on “constitutive” secretion of hexosaminidase and interleukin-16 (IL-16). Compared to untreated control cells, HMC-1 cells incubated with TcdB for 3–24 h exhibited a significant reduction of the mean absolute and relative C m increase in response to free-Ca 2+ and GTPγS suggesting an inhibition of secretory processes by TcdB. In conclusion, the HMC-1 cell line represents a suitable model for the study of direct effects of C. difficile toxins on human mast cell secretory activity

  12. Brown spider dermonecrotic toxin directly induces nephrotoxicity

    International Nuclear Information System (INIS)

    Chaim, Olga Meiri; Sade, Youssef Bacila; Bertoni da Silveira, Rafael; Toma, Leny; Kalapothakis, Evanguedes; Chavez-Olortegui, Carlos; Mangili, Oldemir Carlos; Gremski, Waldemiro; Dietrich, Carl Peter von; Nader, Helena B.; Sanches Veiga, Silvio

    2006-01-01

    Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from

  13. Alpha toxin specific PCR for detection of toxigenic strains of Clostridium perfringens in Poultry

    Directory of Open Access Journals (Sweden)

    Malmarugan Shanmugasamy

    2012-12-01

    Full Text Available Aim : Isolation of clostridium perfirngens from necrotic enteritis cases in poultry and confirmation by alpha toxin specific PCR Materials and methods: Robertson cooked meat medium with Brain Heart Infusion broth was used for isolation of C. perfringens from intestinal contents of necrotic enteritis suspected birds. Positive cultures from perfringens agar were further confirmed by biochemical tests and subjected to alpha toxin specific PCR. Results: Twenty Clostridium perfringens isolates were isolated from intestinal contents of thirty five NE suspected birds. Out of the twenty isolates, fourteen were isolated from commercial broilers of 2 to 6 wk of age and six from commercial layers of 9 to 15 wk of age. Frequency of isolation of C. perfringens was more with Robertson cooked meat medium with BHI broth than thioglycollate broth alone. When positive cultures were streaked on to clostridial agar appreciable luxuriant growths were obtained and the selective streaking of these colonies on perfringens agar with supplements revealed rough and black colonies with sulphate reduction. The isolates produced rough and black colonies with sulphate reduction on perfringens agar, double zone haemolysis on sheep blood agar, stormy clot fermentation on milk medium and opalescence on egg yolk medium. The isolates were found negative for oxidase, catalase, liquefied gelatin, fermented glucose, maltose, lactose and sucrose except mannitol. All the fourteen isolates obtained from commercial broilers proved the alpha toxin producing strains of C. perfringens when they were subjected to alpha toxin specific PCR. Conclusion : This study revealed alpha toxin specific PCR is highly useful for detection of toxigenic strains of Clostridium perfringens in poultry [Vet. World 2012; 5(6.000: 365-368

  14. Interplay between toxin transport and flotillin localization

    DEFF Research Database (Denmark)

    Pust, Sascha; Dyve, Anne Berit; Torgersen, Maria L

    2010-01-01

    The flotillin proteins are localized in lipid domains at the plasma membrane as well as in intracellular compartments. In the present study, we examined the importance of flotillin-1 and flotillin-2 for the uptake and transport of the bacterial Shiga toxin (Stx) and the plant toxin ricin and we...... for flotillin-1 or -2. However, the Golgi-dependent sulfation of both toxins was significantly reduced in flotillin knockdown cells. Interestingly, when the transport of ricin to the ER was investigated, we obtained an increased mannosylation of ricin in flotillin-1 and flotillin-2 knockdown cells. The toxicity...... of both toxins was twofold increased in flotillin-depleted cells. Since BFA (Brefeldin A) inhibits the toxicity even in flotillin knockdown cells, the retrograde toxin transport is apparently still Golgi-dependent. Thus, flotillin proteins regulate and facilitate the retrograde transport of Stx and ricin....

  15. Crystallization of isoelectrically homogeneous cholera toxin

    International Nuclear Information System (INIS)

    Spangler, B.D.; Westbrook, E.M.

    1989-01-01

    Past difficulty in growing good crystals of cholera toxin has prevented the study of the crystal structure of this important protein. The authors have determined that failure of cholera toxin to crystallize well has been due to its heterogeneity. They have now succeeded in overcoming the problem by isolating a single isoelectric variant of this oligomeric protein (one A subunit and five B subunits). Cholera toxin purified by their procedure readily forms large single crystals. The crystal form has been described previously. They have recorded data from native crystals of cholera toxin to 3.0-angstrom resolution with our electronic area detectors. With these data, they have found the orientation of a 5-fold symmetry axis within these crystals, perpendicular to the screw dyad of the crystal. They are now determining the crystal structure of cholera toxin by a combination of multiple heavy-atom isomorphous replacement and density modification techniques, making use of rotational 5-fold averaging of the B subunits

  16. Immunotoxins: The Role of the Toxin

    Directory of Open Access Journals (Sweden)

    David FitzGerald

    2013-08-01

    Full Text Available Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.

  17. Bacterial Signaling to the Nervous System through Toxins and Metabolites.

    Science.gov (United States)

    Yang, Nicole J; Chiu, Isaac M

    2017-03-10

    Mammalian hosts interface intimately with commensal and pathogenic bacteria. It is increasingly clear that molecular interactions between the nervous system and microbes contribute to health and disease. Both commensal and pathogenic bacteria are capable of producing molecules that act on neurons and affect essential aspects of host physiology. Here we highlight several classes of physiologically important molecular interactions that occur between bacteria and the nervous system. First, clostridial neurotoxins block neurotransmission to or from neurons by targeting the SNARE complex, causing the characteristic paralyses of botulism and tetanus during bacterial infection. Second, peripheral sensory neurons-olfactory chemosensory neurons and nociceptor sensory neurons-detect bacterial toxins, formyl peptides, and lipopolysaccharides through distinct molecular mechanisms to elicit smell and pain. Bacteria also damage the central nervous system through toxins that target the brain during infection. Finally, the gut microbiota produces molecules that act on enteric neurons to influence gastrointestinal motility, and metabolites that stimulate the "gut-brain axis" to alter neural circuits, autonomic function, and higher-order brain function and behavior. Furthering the mechanistic and molecular understanding of how bacteria affect the nervous system may uncover potential strategies for modulating neural function and treating neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Protection Against Necrotic Enteritis in Broiler Chickens by Regulated Delayed Lysis Salmonella Vaccines.

    Science.gov (United States)

    Jiang, Yanlong; Mo, Hua; Willingham, Crystal; Wang, Shifeng; Park, Jie-Yeun; Kong, Wei; Roland, Kenneth L; Curtiss, Roy

    2015-12-01

    Necrotic enteritis (NE), caused by Gram-positive Clostridium perfringens type A strains, has gained more attention in the broiler industry due to governmental restrictions affecting the use of growth-promoting antibiotics in feed. To date, there is only one commercial NE vaccine available, based on the C. perfringens alpha toxin. However, recent work has suggested that the NetB toxin, not alpha toxin, is the most critical virulence factor for causing NE. These findings notwithstanding, it is clear from prior research that immune responses against both toxins can provide some protection against NE. In this study, we delivered a carboxyl-terminal fragment of alpha toxin and a GST-NetB fusion protein using a novel attenuated Salmonella vaccine strain designed to lyse after 6-10 rounds of replication in the chicken host. We immunized birds with vaccine strains producing each protein individually, a mixture of the two strains, or with a single vaccine strain that produced both proteins. Immunization with strains producing either of the single proteins was not protective, but immunization with a mixture of the two or with a single strain producing both proteins resulted in protective immunity. The vaccine strain synthesizing both PlcC and GST-NetB was able to elicit strong production of intestinal IgA, IgY, and IgM antibodies and significantly protect broilers against C. perfringens challenge against both mild and severe challenges. Although not part of our experimental plan, the broiler chicks we obtained for these studies were apparently contaminated during transit from the hatchery with group D Salmonella. Despite this drawback, the vaccines worked well, indicating applicability to real-world conditions.

  19. Enteric hyperoxaluria in chronic pancreatitis.

    Science.gov (United States)

    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

  20. Cyanobacterial toxins: risk management for health protection

    International Nuclear Information System (INIS)

    Codd, Geoffrey A.; Morrison, Louise F.; Metcalf, James S.

    2005-01-01

    This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over 45 countries, and in numerous brackish, coastal, and marine environments. The principal toxigenic genera are listed. Known sources of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins, irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in the risk management of cyanobacterial toxins and cells are reviewed, including derivations (where sufficient data are available) of tolerable daily intakes (TDIs) and guideline values (GVs) with reference to the toxins in drinking water, and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties and some gaps in knowledge are also discussed, including the importance of exposure media (animal and plant foods), in addition to potable and recreational waters. Finally, we present an outline of steps to develop and implement risk management strategies for cyanobacterial cells and toxins in waterbodies, with recent applications and the integration of Hazard Assessment Critical Control Point (HACCP) principles

  1. Computational Studies of Snake Venom Toxins.

    Science.gov (United States)

    Ojeda, Paola G; Ramírez, David; Alzate-Morales, Jans; Caballero, Julio; Kaas, Quentin; González, Wendy

    2017-12-22

    Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

  2. Computational Studies of Snake Venom Toxins

    Directory of Open Access Journals (Sweden)

    Paola G. Ojeda

    2017-12-01

    Full Text Available Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

  3. Botulinum toxin for the treatment of bruxism.

    Science.gov (United States)

    Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray

    2015-10-01

    Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.

  4. Engineering toxins for 21st century therapies.

    Science.gov (United States)

    Chaddock, John A; Acharya, K Ravi

    2011-04-01

    'Engineering Toxins for 21st Century Therapies' (9-10 September 2010) was part of the Royal Society International Seminar series held at the Kavli International Centre, UK. Participants were assembled from a range of disciplines (academic, industry, regulatory, public health) to discuss the future potential of toxin-based therapies. The meeting explored how the current structural and mechanistic knowledge of toxins could be used to engineer future toxin-based therapies. To date, significant progress has been made in the design of novel recombinant biologics based on domains of natural toxins, engineered to exhibit advantageous properties. The meeting concluded, firstly that future product development vitally required the appropriate combination of creativity and innovation that can come from the academic, biotechnology and pharma sectors. Second, that continued investigation into understanding the basic science of the toxins and their targets was essential in order to develop new opportunities for the existing products and to create new products with enhanced properties. Finally, it was concluded that the clinical potential for development of novel biologics based on toxin domains was evident. © 2011 The Authors Journal compilation © 2011 FEBS.

  5. Role of Botulinum Toxin in Depression.

    Science.gov (United States)

    Parsaik, Ajay K; Mascarenhas, Sonia S; Hashmi, Aqeel; Prokop, Larry J; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

    2016-03-01

    The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression. We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic. Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo. This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

  6. Botulinum toxin: yesterday, today, tomorrow

    Directory of Open Access Journals (Sweden)

    A. R. Artemenko

    2013-01-01

    Full Text Available Botulinum toxin (BoNT is a bacterial neurotoxin presented with seven serotypes that inhibit neurotransmitter release from nerve endings. The serotypes of BoNT are antigenically dissimilar, act via different, but interconnected mechanisms, and are not interchangeable. The activity of BoNT is associated with impaired neuroexocytosis occurring in several steps: from the binding of BoNT to its specific receptor on the axon terminal membrane to the proteolytic enzymatic cleavage of SNARE substrate. The effect of BoNT is considered to be restricted to the peripheral nervous system, but when given in particularly high doses, it has been recently shown to affect individual brain structures. In addition, by modulating peripheral afferentation, BoNT may influence the excitability of central neuronal structures at both spinal and cortical levels. Only BoNT serotypes A and B are used in clinical practice and aesthetic medicine. The type A has gained the widest acceptance as a therapeutic agent for more than 100 abnormalities manifesting themselves as muscular hyperactivity, hyperfunction of endocrine gland, and chronic pain. The effect of BoNT preparations shows itself 2-5 days after injection, lasts 3 months or more, and gradually decreases with as a result of pharmacokinetic and intracellular reparative processes. Biotechnology advances and potentialities allow purposefully modification of the protein molecular structure of BoNT, which expands the use and efficiency of performed therapy with neurotoxins. Recombinant technologies provide a combination of major therapeutic properties of each used BoNT serotype and expand indications for recombinant chimeric toxins.

  7. Toxin production in Dinophysis and the fate of these toxins in marine mussels

    DEFF Research Database (Denmark)

    Nielsen, Lasse Tor

    Diarrhetic shellfish poisoning (DSP) poses a considerable threat to food safety and to the economy of shellfish fishers and farmers in many parts of the world. Thousands of DSP intoxications have been reported, and bivalve harvesting can sometimes be closed down several months in a row. The toxins....... acuta. I grew the two species in laboratory cultures at different irradiances (7-130 μmol photons m-2 s-1) and with different food availability. The results showed that irradiance had no effects on toxin profiles, and only limited effects of the cellular toxin contents. Rather, toxin production rates...... are primarily produced by the marine mixotrophic dinoflagellates Dinophysis spp., known to occur in most parts of the world. Dinophysis can, along with other planktonic organisms, be consumed by filter-feeding bivalves, and thus the toxins can accumulate. Dinophysis can produce the three toxin groups, okadaic...

  8. Conditional Toxin Splicing Using a Split Intein System.

    Science.gov (United States)

    Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L

    2017-01-01

    Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.

  9. Enteral Nutrition and Acute Pancreatitis: A Review

    NARCIS (Netherlands)

    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

  10. Understanding and controlling the enteric nervous system

    NARCIS (Netherlands)

    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

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

    African Journals Online (AJOL)

    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 ...

  12. NNDSS - Table II. Shiga toxin to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Shiga toxin to Shigellosis - 2015. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  13. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of resistant pathogens.

  14. Bacterial toxins as pathogen weapons against phagocytes

    Directory of Open Access Journals (Sweden)

    Ana edo Vale

    2016-02-01

    Full Text Available Bacterial toxins are virulence factors that manipulate host cell functions and take over the control of vital processes of living organisms to favour microbial infection. Some toxins directly target innate immune cells, thereby annihilating a major branch of the host immune response. In this review we will focus on bacterial toxins that act from the extracellular milieu and hinder the function of macrophages and neutrophils. In particular, we will concentrate on toxins from Gram-positive and Gram-negative bacteria that manipulate cell signalling or induce cell death by either imposing direct damage to the host cells cytoplasmic membrane or enzymatically modifying key eukaryotic targets. Outcomes regarding pathogen dissemination, host damage and disease progression will be discussed.

  15. How Parkinsonian Toxins Dysregulate the Autophagy Machinery

    Directory of Open Access Journals (Sweden)

    Ruben K. Dagda

    2013-11-01

    Full Text Available Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone have been widely employed as in vivo and in vitro chemical models of Parkinson’s disease (PD. Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD.

  16. Botulinum toxin type a for chronic migraine.

    Science.gov (United States)

    Ashkenazi, Avi

    2010-03-01

    Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.

  17. NNDSS - Table II. Shiga toxin to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Shiga toxin to Shigellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  18. Updates on tetanus toxin: a fundamental approach

    Directory of Open Access Journals (Sweden)

    Md. Ahaduzzaman

    2015-03-01

    Full Text Available Clostridium tetani is an anaerobic bacterium that produces second most poisonous protein toxins than any other bacteria. Tetanus in animals is sporadic in nature but difficult to combat even by using antibiotics and antiserum. It is crucial to understand the fundamental mechanisms and signals that control toxin production for advance research and medicinal uses. This review was intended for better understanding the basic patho-physiology of tetanus and neurotoxins (TeNT among the audience of related field.

  19. Botulinum toxin therapy for limb dystonias.

    Science.gov (United States)

    Yoshimura, D M; Aminoff, M J; Olney, R K

    1992-03-01

    We investigated the effectiveness of botulinum toxin in 17 patients with limb dystonias (10 with occupational cramps, three with idiopathic dystonia unrelated to activity, and two each with post-stroke and parkinsonian dystonia) in a placebo-controlled, blinded study. We identified affected muscles clinically and by recording the EMG from implanted wire electrodes at rest and during performance of tasks that precipitated abnormal postures. There were three injections given with graded doses of toxin (average doses, 5 to 10, 10 to 20, and 20 to 40 units per muscle) and one with placebo, in random order. Subjective improvement occurred after 53% of injections of botulinum toxin, and this was substantial in 24%. Only one patient (7%) improved after placebo injection. Subjective improvement occurred in 82% of patients with at least one dose of toxin, lasting for 1 to 4 months. Response rates were similar between clinical groups. Objective evaluation failed to demonstrate significant improvement following treatment with toxin compared with placebo. The major side effect was transient focal weakness after 53% of injections of toxin.

  20. Botulinum toxin for the treatment of strabismus.

    Science.gov (United States)

    Rowe, Fiona J; Noonan, Carmel P

    2017-03-02

    The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus. The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We handsearched the British and Irish Orthoptic Journal, Australian Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and International Orthoptic Association (IOA) (www.liv.ac.uk/orthoptics/research/search.htm) and American Academy of Paediatric Ophthalmology and Strabismus meetings (AAPOS). We contacted researchers who are active in this field for information about further

  1. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    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

  2. Enteral nutrition in inflammatory bowel disease.

    Science.gov (United States)

    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

  3. Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

    Energy Technology Data Exchange (ETDEWEB)

    Habermann, E [Giessen Univ. (Germany, F.R.). Pharmakologisches Inst.

    1976-01-01

    /sup 125/I-labelled tetanus toxin and /sup 125/I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin.

  4. Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum A toxin on synaptosomes, and differentiation of their acceptors

    International Nuclear Information System (INIS)

    Habermann, E.

    1976-01-01

    125 I-labelled tetanus toxin and 125 I-labelled botulinum A neurotoxin are known to be specifically bound to brain synaptosomes. In order to discriminate between active toxin and inactive admixtures present in the starting material or arising during iodination, synaptosome columns were prepared using bromacetylcellulose and/or kieselgur (Celite) as carriers. Both types of columns adsorb the toxins from low ionic strength medium and release them if the pH and ionic strength are raised. Botulinum toxin was eluted with lower ionic strength than tetanus toxin, and could be freed from nontoxic admixtures. Analysis by affinity chromatography disclosed partially toxoided tetanus toxin in both labelled and unlabelled toxin samples. High concentrations of formaldehyde (0.5%) destroyed both toxicity and affinity to the synaptosomes of tetanus toxin. Low concentrations of formaldehyde (0.05%) yielded a derivative of low toxicity which was still, however less firmly, bound to synaptosomes. Tetanus and botulinum toxin differ by their acceptors. Whereas unlabelled botulinum toxin is unable to compete with labelled tetanus toxin, unlabelled tetanus toxin slightly competes with botulinum toxin. Both labelled toxins display anomalous binding behaviour in that they cannot be displaced completely even with a large excess of unlabelled toxin. (orig.) [de

  5. Botulinum toxin in parkinsonism: The when, how, and which for botulinum toxin injections.

    Science.gov (United States)

    Cardoso, Francisco

    2018-06-01

    The aim of this article is to provide a review of the use of injections of botulinum toxin in the management of selected symptoms and signs of Parkinson's disease and other forms of parkinsonism. Sialorrhea is defined as inability to control oral secretions, resulting in excessive saliva in the oropharynx. There is a high level of evidence for the treatment of sialorrhea in parkinsonism with injections of different forms of botulinum toxin type A as well as botulinum toxin type B. Tremor can be improved by the use of botulinum toxin injections but improved tremor control often leads to concomitant motor weakness, limiting its use. Levodopa induced dyskinesias are difficult to treat with botulinum toxin injections because of their variable frequency and direction. Apraxia of eyelid opening, a sign more commonly seen in progressive supranuclear palsy and other tauopathies, often improves after botulinum toxin injections. Recent data suggest that regardless of the underlying mechanism, pain in parkinsonism can be alleviated by botulinum toxin injections. Finally, freezing of gait, camptocormia and Pisa syndrome in parkinsonism almost invariably fail to respond to botulinum toxin injections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. American Society for Parenteral & Enteral Nutrition

    Science.gov (United States)

    ... 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 ...

  7. Do enteric neurons make hypocretin? ☆

    Science.gov (United States)

    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

  8. OCCURRENCE OF ENTERIC VIRUSES IN SURFACE WATERS

    Science.gov (United States)

    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...

  9. effects of enteral glutamine supplementation on reduction

    African Journals Online (AJOL)

    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.

  10. [Indications and practice of enteral nutrition].

    Science.gov (United States)

    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.

  11. Do enteric neurons make hypocretin? ☆

    OpenAIRE

    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...

  12. Single toxin dose-response models revisited

    Energy Technology Data Exchange (ETDEWEB)

    Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

    2017-01-01

    The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

  13. Laboratory Screening for Children Entering Foster Care.

    Science.gov (United States)

    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.

  14. The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death

    Directory of Open Access Journals (Sweden)

    Mohamed Siyabeldin E. Ahmed

    2013-05-01

    Full Text Available Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i. Erythrocytes could be sensitized to cytosolic Ca2+ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. Results: A 48 h exposure to acrolein (30 - 50 µM did not significantly modify [Ca2+]i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 µM induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca2+. Acrolein augmented the annexin-V-binding following treatment with Ca2+ ionophore ionomycin (1 µM. Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca2+.

  15. Botulinum Toxin in Management of Limb Tremor

    Directory of Open Access Journals (Sweden)

    Elina Zakin

    2017-11-01

    Full Text Available Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle that has allowed for success in the management of tremors.

  16. Array biosensor for detection of toxins

    Science.gov (United States)

    Ligler, Frances S.; Taitt, Chris Rowe; Shriver-Lake, Lisa C.; Sapsford, Kim E.; Shubin, Yura; Golden, Joel P.

    2003-01-01

    The array biosensor is capable of detecting multiple targets rapidly and simultaneously on the surface of a single waveguide. Sandwich and competitive fluoroimmunoassays have been developed to detect high and low molecular weight toxins, respectively, in complex samples. Recognition molecules (usually antibodies) were first immobilized in specific locations on the waveguide and the resultant patterned array was used to interrogate up to 12 different samples for the presence of multiple different analytes. Upon binding of a fluorescent analyte or fluorescent immunocomplex, the pattern of fluorescent spots was detected using a CCD camera. Automated image analysis was used to determine a mean fluorescence value for each assay spot and to subtract the local background signal. The location of the spot and its mean fluorescence value were used to determine the toxin identity and concentration. Toxins were measured in clinical fluids, environmental samples and foods, with minimal sample preparation. Results are shown for rapid analyses of staphylococcal enterotoxin B, ricin, cholera toxin, botulinum toxoids, trinitrotoluene, and the mycotoxin fumonisin. Toxins were detected at levels as low as 0.5 ng mL(-1).

  17. Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

    Science.gov (United States)

    Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

    2014-12-19

    In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (seawater at high and low salinity but not in seawater at medium salinity, which demonstrated that the toxin molecules entered into micropores and mesopores (below 10nm in size) in seawaters of high and low salinity. More toxin or other matrix agglomerates were displayed on the surface of resin deployed in the seawater of medium salinity. Taking into consideration the pore-size distribution and surface images, it appears that intra-particle diffusion governs toxin adsorption in seawater at high salinity while film diffusion mainly controls the adsorption process in seawater at medium salinity. This is the first study to confirm that molecules of OA and DTX1 are able to enter into micropores (seawater with high salinity (∼27‰). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Mechanism of Shiga Toxin Clustering on Membranes

    DEFF Research Database (Denmark)

    Pezeshkian, Weria; Gao, Haifei; Arumugam, Senthil

    2017-01-01

    between them. The precise mechanism by which this clustering occurs remains poorly defined. Here, we used vesicle and cell systems and computer simulations to show that line tension due to curvature, height, or compositional mismatch, and lipid or solvent depletion cannot drive the clustering of Shiga...... toxin molecules. By contrast, in coarse-grained computer simulations, a correlation was found between clustering and toxin nanoparticle-driven suppression of membrane fluctuations, and experimentally we observed that clustering required the toxin molecules to be tightly bound to the membrane surface...... molecules (several nanometers), and persist even beyond. This force is predicted to operate between manufactured nanoparticles providing they are sufficiently rigid and tightly bound to the plasma membrane, thereby suggesting a route for the targeting of nanoparticles to cells for biomedical applications....

  19. Update on botulinum toxin and dermal fillers.

    Science.gov (United States)

    Berbos, Zachary J; Lipham, William J

    2010-09-01

    The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

  20. Marine toxins and their toxicological significance: An overview

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.

    , Hemolysins-1 and hemolysin-2, saxitoxin, neosaxitoxin, gonyautoxin, tetrodotoxin, ptychodiscus brevis toxin and theonellamide F. According to their mode of action, these toxins are classified into different categories such as cytotoxin, enterotoxin...

  1. Vth Pan American Symposium on Animal, Plant and Microbial Toxins

    National Research Council Canada - National Science Library

    Ownby, Charlotte

    1996-01-01

    .... Presentations on arthropod toxins included work on scorpion neurotoxins, K+ channel-blocking peptides, lice and wasp proteins, stinging insect venom allergens and Australian funnel-web spider toxins...

  2. Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin

    Directory of Open Access Journals (Sweden)

    Masaya Takehara

    2017-08-01

    Full Text Available Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

  3. Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro

    2017-08-11

    Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

  4. Therapeutic Approaches of Botulinum Toxin in Gynecology

    OpenAIRE

    Marius Alexandru Moga; Oana Gabriela Dimienescu; Andreea Bălan; Ioan Scârneciu; Barna Barabaș; Liana Pleș

    2018-01-01

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT...

  5. The spectrum of radiation enteritis: surgical considerations

    International Nuclear Information System (INIS)

    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

  6. Enteric alpha defensins in norm and pathology

    Directory of Open Access Journals (Sweden)

    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.

  7. The radiological features of chronic radiation enteritis

    International Nuclear Information System (INIS)

    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)

  8. 77 FR 9888 - Shiga Toxin-Producing Escherichia coli

    Science.gov (United States)

    2012-02-21

    ... Toxin-Producing Escherichia coli in Certain Raw Beef Products AGENCY: Food Safety and Inspection Service... toxin-producing Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, and O145). This new date..., that are contaminated with Shiga toxin-producing Escherichia coli (STEC) O26, O45, O103, O111, O121...

  9. Military Importance of Natural Toxins and Their Analogs.

    Science.gov (United States)

    Pitschmann, Vladimír; Hon, Zdeněk

    2016-04-28

    Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    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...

  12. VapC toxins drive cellular dormancy under uranium stress for the extreme thermoacidophile Metallosphaera prunae.

    Science.gov (United States)

    Mukherjee, Arpan; Wheaton, Garrett H; Counts, James A; Ijeomah, Brenda; Desai, Jigar; Kelly, Robert M

    2017-07-01

    When abruptly exposed to toxic levels of hexavalent uranium, the extremely thermoacidophilic archaeon Metallosphaera prunae, originally isolated from an abandoned uranium mine, ceased to grow, and concomitantly exhibited heightened levels of cytosolic ribonuclease activity that corresponded to substantial degradation of cellular RNA. The M. prunae transcriptome during 'uranium-shock' implicated VapC toxins as possible causative agents of the observed RNA degradation. Identifiable VapC toxins and PIN-domain proteins encoded in the M. prunae genome were produced and characterized, three of which (VapC4, VapC7, VapC8) substantially degraded M. prunae rRNA in vitro. RNA cleavage specificity for these VapCs mapped to motifs within M. prunae rRNA. Furthermore, based on frequency of cleavage sequences, putative target mRNAs for these VapCs were identified; these were closely associated with translation, transcription, and replication. It is interesting to note that Metallosphaera sedula, a member of the same genus and which has a nearly identical genome sequence but not isolated from a uranium-rich biotope, showed no evidence of dormancy when exposed to this metal. M. prunae utilizes VapC toxins for post-transcriptional regulation under uranium stress to enter a cellular dormant state, thereby providing an adaptive response to what would otherwise be a deleterious environmental perturbation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.

    Science.gov (United States)

    Wu, Yu; Pons, Valérie; Goudet, Amélie; Panigai, Laetitia; Fischer, Annette; Herweg, Jo-Ana; Kali, Sabrina; Davey, Robert A; Laporte, Jérôme; Bouclier, Céline; Yousfi, Rahima; Aubenque, Céline; Merer, Goulven; Gobbo, Emilie; Lopez, Roman; Gillet, Cynthia; Cojean, Sandrine; Popoff, Michel R; Clayette, Pascal; Le Grand, Roger; Boulogne, Claire; Tordo, Noël; Lemichez, Emmanuel; Loiseau, Philippe M; Rudel, Thomas; Sauvaire, Didier; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien

    2017-11-14

    Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

  14. Fate of Fusarium Toxins during Brewing.

    Science.gov (United States)

    Habler, Katharina; Geissinger, Cajetan; Hofer, Katharina; Schüler, Jan; Moghari, Sarah; Hess, Michael; Gastl, Martina; Rychlik, Michael

    2017-01-11

    Some information is available about the fate of Fusarium toxins during the brewing process, but only little is known about the single processing steps in detail. In our study we produced beer from two different barley cultivars inoculated with three different Fusarium species, namely, Fusarium culmorum, Fusarium sporotrichioides, and Fusarium avenaceum, producing a wide range of mycotoxins such as type B trichothecenes, type A trichothecenes, and enniatins. By the use of multi-mycotoxin LC-MS/MS stable isotope dilution methods we were able to follow the fate of Fusarium toxins during the entire brewing process. In particular, the type B trichothecenes deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol showed similar behaviors. Between 35 and 52% of those toxins remained in the beer after filtration. The contents of the potentially hazardous deoxynivalenol-3-glucoside and the type A trichothecenes increased during mashing, but a rapid decrease of deoxynivalenol-3-glucoside content was found during the following steps of lautering and wort boiling. The concentration of enniatins greatly decreased with the discarding of spent grains or finally with the hot break. The results of our study show the retention of diverse Fusarium toxins during the brewing process and allow for assessing the food safety of beer regarding the monitored Fusarium mycotoxins.

  15. Botulinum Toxin in Neurogenic Detrusor Overactivity

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Levi D'Ancona

    2012-09-01

    Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

  16. Bioengineered kidney tubules efficiently excrete uremic toxins

    NARCIS (Netherlands)

    Jansen, Jitske; Fedecostante, M.; Wilmer, M.; Peters, J.G.; Kreuser, U.M.; Broek, P.H.; Mensink, R.A.; Boltje, T.J.; Stamatialis, Dimitrios; Wetzels, J.F.; van der Heuvel, L.P.; Hoenderop, J.G.; Masereeuw, R.

    2016-01-01

    The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed

  17. Treatment diary for botulinum toxin spasticity treatment

    DEFF Research Database (Denmark)

    Biering-Sørensen, Bo; Iversen, Helle K; Frederiksen, Inge M S

    2017-01-01

    The aim of this study is to develop a treatment diary for patients receiving spasticity treatment including botulinum toxin injection and physiotherapy and/or occupational therapy. The diary focuses on problems triggered by skeletal muscle overactivity; agreed goals for treatment and the patient...

  18. Diffusion, spread, and migration of botulinum toxin.

    Science.gov (United States)

    Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

    2013-11-01

    Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. © 2013 International Parkinson and Movement Disorder Society.

  19. Isolated Enteric Cyst in the Neck

    Directory of Open Access Journals (Sweden)

    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.

  20. Hypophosphatemia associated with enteral alimentation in cats.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    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

  3. Entering a Crack: An Encounter with Gossip

    Science.gov (United States)

    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.…

  4. Kokainudløst iskaemisk enteritis

    DEFF Research Database (Denmark)

    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...

  5. Astronaut John Glenn Enters Friendship 7

    Science.gov (United States)

    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.

  6. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    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

  7. Mutant with diphtheria toxin receptor and acidification function but defective in entry of toxin

    International Nuclear Information System (INIS)

    Kohno, Kenji; Hayes, H.; Mekada, Eisuke; Uchida, Tsuyoshi

    1987-01-01

    A mutant of Chinese hamster ovary cells, GE1, that is highly resistant to diphtheria toxin was isolated. The mutant contains 50% ADP-ribosylatable elongation factor 2, but its protein synthesis was not inhibited by the toxin even at concentrations above 100 μg/ml. 125 I-labeled diphtheria toxin was associated with GE1 cells as well as with the parent cells but did not block protein synthesis of GE1 cells even when the cells were exposed to low pH in the presence or absence of NH 4 Cl. The infections of GE1 cells and the parent cells by vesicular stomatitis virus were similar. GE1 cells were cross-resistant to Pseudomonas aeruginosa exotoxin A and so were about 1,000 times more resistant to this toxin than the parent cells. Hybrids of GE1 cells and the parent cells or mutant cells lacking a functional receptor were more sensitive to diphtheria toxin than GE1 cells. These results suggest that entry of diphtheria toxin into cells requires a cellular factor(s) in addition to those involved in receptor function and acidification of endosomes and that GE1 cells do not express this cellular factor. This character is recessive in GE1 cells

  8. Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

    International Nuclear Information System (INIS)

    Won, JaeSeon; Nam, PilWon; Lee, YongChan; Choe, MuHyeon

    2009-01-01

    Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G 4 S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38] 2 ) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

  9. Molecular Modeling and docking of Wheat Hydroquinone Glucosyl transferase by using Hydroquinone, Phenyl phosphorodiamate and n-(n butyl) Phosphorothiocic Triamide as Inhibitors

    Science.gov (United States)

    Huma, Tayyaba; Maryam, Arooma; qamar, Tahir ul

    2014-01-01

    In agriculture high urease activity during urea fertilization causes substantial environmental and economical problems by releasing abnormally large amount of ammonia into the atmosphere which leads to plant damage as well as ammonia toxicity. All over the world, urea is the most widely applied nitrogen fertilizer. Due to the action of enzyme urease; urea nitrogen is lost as volatile ammonia. For efficient use of nitrogen fertilizer, urease inhibitor along with the urea fertilizer is one of the best promising strategies. Urease inhibitors also provide an insight in understanding the mechanism of enzyme catalyzed reaction, the role of various amino acids in catalytic activity present at the active site of enzyme and the importance of nickel to this metallo enzyme. By keeping it in view, the present study was designed to dock three urease inhibitors namely Hydroquinone (HQ), Phenyl Phosphorodiamate (PPD) and N-(n-butyl) Phosphorothiocic triamide (NBPT) against Hydroquinone glucosyltransferase using molecular docking approach. The 3D structure of Hydroquinone glucosyltransferase was predicted using homology modeling approach and quality of the structure was assured using Ramachandran plot. This study revealed important interactions among the urease inhibitors and Hydroquinone glucosyltransferase. Thus, it can be inferred that these inhibitors may serve as future anti toxic constituent against plant toxins. PMID:24748751

  10. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  11. Discovery of novel bacterial toxins by genomics and computational biology.

    Science.gov (United States)

    Doxey, Andrew C; Mansfield, Michael J; Montecucco, Cesare

    2018-06-01

    Hundreds and hundreds of bacterial protein toxins are presently known. Traditionally, toxin identification begins with pathological studies of bacterial infectious disease. Following identification and cultivation of a bacterial pathogen, the protein toxin is purified from the culture medium and its pathogenic activity is studied using the methods of biochemistry and structural biology, cell biology, tissue and organ biology, and appropriate animal models, supplemented by bioimaging techniques. The ongoing and explosive development of high-throughput DNA sequencing and bioinformatic approaches have set in motion a revolution in many fields of biology, including microbiology. One consequence is that genes encoding novel bacterial toxins can be identified by bioinformatic and computational methods based on previous knowledge accumulated from studies of the biology and pathology of thousands of known bacterial protein toxins. Starting from the paradigmatic cases of diphtheria toxin, tetanus and botulinum neurotoxins, this review discusses traditional experimental approaches as well as bioinformatics and genomics-driven approaches that facilitate the discovery of novel bacterial toxins. We discuss recent work on the identification of novel botulinum-like toxins from genera such as Weissella, Chryseobacterium, and Enteroccocus, and the implications of these computationally identified toxins in the field. Finally, we discuss the promise of metagenomics in the discovery of novel toxins and their ecological niches, and present data suggesting the existence of uncharacterized, botulinum-like toxin genes in insect gut metagenomes. Copyright © 2018. Published by Elsevier Ltd.

  12. Radioimmunoassay for yeast killer toxin from Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Siddiqui, F.A.; Bussey, H.

    1981-01-01

    A radioimmunoassay was developed for the K1 killer toxin from strain T158C/S14a of Saccharomyces cerevisiae. Iodine 125-labelled toxin was made to a specific activity of 100 μCi/mg of protein. Antibody to purified toxin was prepared in rabbits using toxin cross-linked to itself. These antibodies, partially purified by 50 percent ammonium sulfate precipitation and Sepharose CL-6B column chromatography, produced one precipitation band with killer toxin and bound 125 I-labelled toxin in a radioimmunoassay. The antibody preparation also bound with the toxins from another K1 killer, A364A, and three chromosomal superkiller mutants derived from it. (auth)

  13. Convergent use of RhoGAP toxins by eukaryotic parasites and bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Dominique Colinet

    2007-12-01

    Full Text Available Inactivation of host Rho GTPases is a widespread strategy employed by bacterial pathogens to manipulate mammalian cellular functions and avoid immune defenses. Some bacterial toxins mimic eukaryotic Rho GTPase-activating proteins (GAPs to inactivate mammalian GTPases, probably as a result of evolutionary convergence. An intriguing question remains whether eukaryotic pathogens or parasites may use endogenous GAPs as immune-suppressive toxins to target the same key genes as bacterial pathogens. Interestingly, a RhoGAP domain-containing protein, LbGAP, was recently characterized from the parasitoid wasp Leptopilina boulardi, and shown to protect parasitoid eggs from the immune response of Drosophila host larvae. We demonstrate here that LbGAP has structural characteristics of eukaryotic RhoGAPs but that it acts similarly to bacterial RhoGAP toxins in mammals. First, we show by immunocytochemistry that LbGAP enters Drosophila immune cells, plasmatocytes and lamellocytes, and that morphological changes in lamellocytes are correlated with the quantity of LbGAP they contain. Demonstration that LbGAP displays a GAP activity and specifically interacts with the active, GTP-bound form of the two Drosophila Rho GTPases Rac1 and Rac2, both required for successful encapsulation of Leptopilina eggs, was then achieved using biochemical tests, yeast two-hybrid analysis, and GST pull-down assays. In addition, we show that the overall structure of LbGAP is similar to that of eukaryotic RhoGAP domains, and we identify distinct residues involved in its interaction with Rac GTPases. Altogether, these results show that eukaryotic parasites can use endogenous RhoGAPs as virulence factors and that despite their differences in sequence and structure, eukaryotic and bacterial RhoGAP toxins are similarly used to target the same immune pathways in insects and mammals.

  14. General synthesis of β-alanine-containing spider polyamine toxins and discovery of nephila polyamine toxins 1 and 8 as highly potent inhibitors of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Lucas, Simon; Poulsen, Mette H; Nørager, Niels G

    2012-01-01

    Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotrop...

  15. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

    Science.gov (United States)

    Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

    2016-03-01

    Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

  16. Enteric methane emissions from German pigs

    DEFF Research Database (Denmark)

    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...

  17. Clinical and nutritional implications of radiation enteritis

    International Nuclear Information System (INIS)

    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

  18. Clinical and nutritional implications of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Effects of entering adulthood during a recession

    OpenAIRE

    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...

  20. Enteral Nutrition in Dementia: A Systematic Review

    Directory of Open Access Journals (Sweden)

    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.

  1. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  2. Toxins for Transgenic Resistance to Hemipteran Pests

    Science.gov (United States)

    Chougule, Nanasaheb P.; Bonning, Bryony C.

    2012-01-01

    The sap sucking insects (Hemiptera), which include aphids, whiteflies, plant bugs and stink bugs, have emerged as major agricultural pests. The Hemiptera cause direct damage by feeding on crops, and in some cases indirect damage by transmission of plant viruses. Current management relies almost exclusively on application of classical chemical insecticides. While the development of transgenic crops expressing toxins derived from the bacterium Bacillus thuringiensis (Bt) has provided effective plant protection against some insect pests, Bt toxins exhibit little toxicity against sap sucking insects. Indeed, the pest status of some Hemiptera on Bt-transgenic plants has increased in the absence of pesticide application. The increased pest status of numerous hemipteran species, combined with increased prevalence of resistance to chemical insecticides, provides impetus for the development of biologically based, alternative management strategies. Here, we provide an overview of approaches toward transgenic resistance to hemipteran pests. PMID:22822455

  3. Therapeutic Approaches of Botulinum Toxin in Gynecology.

    Science.gov (United States)

    Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

    2018-04-21

    Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  4. Therapeutic Approaches of Botulinum Toxin in Gynecology

    Directory of Open Access Journals (Sweden)

    Marius Alexandru Moga

    2018-04-01

    Full Text Available Botulinum toxins (BoNTs are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G. Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

  5. The Biology of the Cytolethal Distending Toxins

    Directory of Open Access Journals (Sweden)

    Teresa Frisan

    2011-03-01

    Full Text Available The cytolethal distending toxins (CDTs, produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B2 toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.

  6. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  7. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin

    Science.gov (United States)

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R.; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

    2016-01-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins. PMID:27043629

  8. [Botulinum toxin: An important complement for facial rejuvenation surgery].

    Science.gov (United States)

    Le Louarn, C

    2017-10-01

    The improved understanding of the functional anatomy of the face and of the action of the botulinum toxin A leads us to determine a new injection procedure which consequently decreases the risk of eyebrow and eyelid ptosis and increases the toxin's injection possibilities and efficiencies. With less units of toxin, the technique herein described proposes to be more efficient on more muscles: variable toxin injections concentration adapted to each injected muscle are used. Thanks to a new procedure in the upper face, toxin A injection can be quite close to an endoscopic surgical action. In addition, interesting results are achievable to rejuvenate the lateral canthus with injection on the upper lateral tarsus, to rejuvenate the nose with injection at the alar base, the jawline and the neck region. Lastly, a smoothing effect on the skin (meso botox) is obtained by the anticholinergic action of the toxin A on the dermal receptors. Copyright © 2017. Published by Elsevier Masson SAS.

  9. AB toxins: a paradigm switch from deadly to desirable.

    Science.gov (United States)

    Odumosu, Oludare; Nicholas, Dequina; Yano, Hiroshi; Langridge, William

    2010-07-01

    To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.

  10. Recent Insights into Clostridium perfringens Beta-Toxin

    Directory of Open Access Journals (Sweden)

    Masahiro Nagahama

    2015-02-01

    Full Text Available Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.

  11. Transgastrostomy jejunal intubation for enteric alimentation.

    Science.gov (United States)

    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.

  12. Cnidarian Toxins Acting on Voltage-Gated Ion Channels

    Directory of Open Access Journals (Sweden)

    Robert M. Greenberg

    2006-04-01

    Full Text Available Abstract: Voltage-gated ion channels generate electrical activity in excitable cells. As such, they are essential components of neuromuscular and neuronal systems, and are targeted by toxins from a wide variety of phyla, including the cnidarians. Here, we review cnidarian toxins known to target voltage-gated ion channels, the specific channel types targeted, and, where known, the sites of action of cnidarian toxins on different channels.

  13. Bacterial toxin-antitoxin systems: more than selfish entities?

    OpenAIRE

    Laurence Van Melderen; Manuel Saavedra De Bast

    2009-01-01

    Bacterial toxin?antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence,...

  14. Military Importance of Natural Toxins and Their Analogs

    Directory of Open Access Journals (Sweden)

    Vladimír Pitschmann

    2016-04-01

    Full Text Available Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots; it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

  15. Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue

    Directory of Open Access Journals (Sweden)

    Bryan J. Berube

    2013-06-01

    Full Text Available Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of α-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as α-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for α-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on α-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of α-toxin in modulation of the complex interaction of S. aureus with its human host.

  16. Biotransformation modulation and genotoxicity in white seabream upon exposure to paralytic shellfish toxins produced by Gymnodinium catenatum

    International Nuclear Information System (INIS)

    Reis Costa, Pedro; Pereira, Patrícia; Guilherme, Sofia; Barata, Marisa; Nicolau, Lídia; Santos, Maria Ana; Pacheco, Mário; Pousão-Ferreira, Pedro

    2012-01-01

    Fish are recurrently exposed to paralytic shellfish toxins (PSTs) produced by Gymnodinium catenatum. Nevertheless, the knowledge regarding metabolism of PSTs and their toxic effects in fish is scarce. Consequently, the current study aims to investigate the role of phase I and II detoxification enzymes on PST metabolism in the liver of white seabream (Diplodus sargus), assessing ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities. Moreover, the genotoxic potential of PSTs was examined through the erythrocytic nuclear abnormality (ENA) assay. Fish were intracoelomically (IC) injected with a nominal dose (expressed as saxitoxin equivalents) of 1.60 μg STXeq kg −1 semipurified from a G. catenatum cell culture with previously determined toxin profile. Fish were sacrificed 2 and 6 days after IC injection. PST levels determined in fish liver were15.2 and 12.2 μg STXeq kg −1 , respectively, at 2 and 6 days after the injection. Though several PSTs were administered, only dcSTX was detected in the liver after 2 and 6 days. This was regarded as an evidence that most of the N-sulfocarbamoyl and decarbamoyl toxins were rapidly biotransformed in D. sargus liver and/or eliminated. This was corroborated by a hepatic GST activity induction at 2 days after injection. Hepatic EROD activity was unresponsive to PSTs, suggesting that these toxins enter phase II of biotransformation directly. The genotoxic potential of PSTs was also demonstrated; these toxins were able to induce cytogenetic damage, such as chromosome (or chromatid) breaks or loss and segregational anomalies, measured by the ENA assay. Overall, this study pointed out the ecological risk associated with the contamination of fish with PSTs generated by G. catenatum blooms, providing the necessary first data for a proper interpretation of biomonitoring programs aiming to assess the impact of phytoplankton blooms in fish.

  17. Biotransformation modulation and genotoxicity in white seabream upon exposure to paralytic shellfish toxins produced by Gymnodinium catenatum

    Energy Technology Data Exchange (ETDEWEB)

    Reis Costa, Pedro, E-mail: prcosta@ipimar.pt [IPIMAR - National Institute for Biological Resources (INRB/IPIMAR), Av. Brasilia, 1449-006 Lisboa (Portugal); Pereira, Patricia [IPIMAR - National Institute for Biological Resources (INRB/IPIMAR), Av. Brasilia, 1449-006 Lisboa (Portugal); Department of Biology and CESAM, Aveiro University, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Guilherme, Sofia [Department of Biology and CESAM, Aveiro University, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Barata, Marisa; Nicolau, Lidia [IPIMAR - National Institute for Biological Resources (INRB/IPIMAR), Av. 5 Outubro, 8700-305 Olhao (Portugal); Santos, Maria Ana; Pacheco, Mario [Department of Biology and CESAM, Aveiro University, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Pousao-Ferreira, Pedro [IPIMAR - National Institute for Biological Resources (INRB/IPIMAR), Av. 5 Outubro, 8700-305 Olhao (Portugal)

    2012-01-15

    Fish are recurrently exposed to paralytic shellfish toxins (PSTs) produced by Gymnodinium catenatum. Nevertheless, the knowledge regarding metabolism of PSTs and their toxic effects in fish is scarce. Consequently, the current study aims to investigate the role of phase I and II detoxification enzymes on PST metabolism in the liver of white seabream (Diplodus sargus), assessing ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities. Moreover, the genotoxic potential of PSTs was examined through the erythrocytic nuclear abnormality (ENA) assay. Fish were intracoelomically (IC) injected with a nominal dose (expressed as saxitoxin equivalents) of 1.60 {mu}g STXeq kg{sup -1} semipurified from a G. catenatum cell culture with previously determined toxin profile. Fish were sacrificed 2 and 6 days after IC injection. PST levels determined in fish liver were15.2 and 12.2 {mu}g STXeq kg{sup -1}, respectively, at 2 and 6 days after the injection. Though several PSTs were administered, only dcSTX was detected in the liver after 2 and 6 days. This was regarded as an evidence that most of the N-sulfocarbamoyl and decarbamoyl toxins were rapidly biotransformed in D. sargus liver and/or eliminated. This was corroborated by a hepatic GST activity induction at 2 days after injection. Hepatic EROD activity was unresponsive to PSTs, suggesting that these toxins enter phase II of biotransformation directly. The genotoxic potential of PSTs was also demonstrated; these toxins were able to induce cytogenetic damage, such as chromosome (or chromatid) breaks or loss and segregational anomalies, measured by the ENA assay. Overall, this study pointed out the ecological risk associated with the contamination of fish with PSTs generated by G. catenatum blooms, providing the necessary first data for a proper interpretation of biomonitoring programs aiming to assess the impact of phytoplankton blooms in fish.

  18. Biotransformation modulation and genotoxicity in white seabream upon exposure to paralytic shellfish toxins produced by Gymnodinium catenatum.

    Science.gov (United States)

    Costa, Pedro Reis; Pereira, Patrícia; Guilherme, Sofia; Barata, Marisa; Nicolau, Lídia; Santos, Maria Ana; Pacheco, Mário; Pousão-Ferreira, Pedro

    2012-01-15

    Fish are recurrently exposed to paralytic shellfish toxins (PSTs) produced by Gymnodinium catenatum. Nevertheless, the knowledge regarding metabolism of PSTs and their toxic effects in fish is scarce. Consequently, the current study aims to investigate the role of phase I and II detoxification enzymes on PST metabolism in the liver of white seabream (Diplodus sargus), assessing ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities. Moreover, the genotoxic potential of PSTs was examined through the erythrocytic nuclear abnormality (ENA) assay. Fish were intracoelomically (IC) injected with a nominal dose (expressed as saxitoxin equivalents) of 1.60 μg STXeq kg⁻¹ semipurified from a G. catenatum cell culture with previously determined toxin profile. Fish were sacrificed 2 and 6 days after IC injection. PST levels determined in fish liver were 15.2 and 12.2 μg STXeq kg⁻¹, respectively, at 2 and 6 days after the injection. Though several PSTs were administered, only dcSTX was detected in the liver after 2 and 6 days. This was regarded as an evidence that most of the N-sulfocarbamoyl and decarbamoyl toxins were rapidly biotransformed in D. sargus liver and/or eliminated. This was corroborated by a hepatic GST activity induction at 2 days after injection. Hepatic EROD activity was unresponsive to PSTs, suggesting that these toxins enter phase II of biotransformation directly. The genotoxic potential of PSTs was also demonstrated; these toxins were able to induce cytogenetic damage, such as chromosome (or chromatid) breaks or loss and segregational anomalies, measured by the ENA assay. Overall, this study pointed out the ecological risk associated with the contamination of fish with PSTs generated by G. catenatum blooms, providing the necessary first data for a proper interpretation of biomonitoring programs aiming to assess the impact of phytoplankton blooms in fish. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Toxins That Affect Voltage-Gated Sodium Channels.

    Science.gov (United States)

    Ji, Yonghua

    2017-10-26

    Voltage-gated sodium channels (VGSCs) are critical in generation and conduction of electrical signals in multiple excitable tissues. Natural toxins, produced by animal, plant, and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolutions. Studying of the diverse interaction between VGSC and VGSC-targeting toxins has been contributing to the increasing understanding of molecular structure and function, pharmacology, and drug development potential of VGSCs. This chapter aims to summarize some of the current views on the VGSC-toxin interaction based on the established receptor sites of VGSC for natural toxins.

  20. Tumor Targeting and Drug Delivery by Anthrax Toxin

    Directory of Open Access Journals (Sweden)

    Christopher Bachran

    2016-07-01

    Full Text Available Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  1. Tumor Targeting and Drug Delivery by Anthrax Toxin.

    Science.gov (United States)

    Bachran, Christopher; Leppla, Stephen H

    2016-07-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

  2. Tumor Targeting and Drug Delivery by Anthrax Toxin

    OpenAIRE

    Bachran, Christopher; Leppla, Stephen H.

    2016-01-01

    Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associ...

  3. Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins.

    Science.gov (United States)

    Mantzouki, Evanthia; Lürling, Miquel; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Seelen, Laura; Teurlincx, Sven; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma; Cillero-Castro, Carmen; Budzyńska, Agnieszka; Goldyn, Ryszard; Kozak, Anna; Rosińska, Joanna; Szeląg-Wasielewska, Elżbieta; Domek, Piotr; Jakubowska-Krepska, Natalia; Kwasizur, Kinga; Messyasz, Beata; Pełechaty, Aleksandra; Pełechaty, Mariusz; Kokocinski, Mikolaj; García-Murcia, Ana; Real, Monserrat; Romans, Elvira; Noguero-Ribes, Jordi; Duque, David Parreño; Fernández-Morán, Elísabeth; Karakaya, Nusret; Häggqvist, Kerstin; Demir, Nilsun; Beklioğlu, Meryem; Filiz, Nur; Levi, Eti E.; Iskin, Uğur; Bezirci, Gizem; Tavşanoğlu, Ülkü Nihan; Özhan, Koray; Gkelis, Spyros; Panou, Manthos; Fakioglu, Özden; Avagianos, Christos; Kaloudis, Triantafyllos; Çelik, Kemal; Yilmaz, Mete; Marcé, Rafael; Catalán, Nuria; Bravo, Andrea G.; Buck, Moritz; Colom-Montero, William; Mustonen, Kristiina; Pierson, Don; Yang, Yang; Raposeiro, Pedro M.; Gonçalves, Vítor; Antoniou, Maria G.; Tsiarta, Nikoletta; McCarthy, Valerie; Perello, Victor C.; Feldmann, Tõnu; Laas, Alo; Panksep, Kristel; Tuvikene, Lea; Gagala, Ilona; Mankiewicz-Boczek, Joana; Yağcı, Meral Apaydın; Çınar, Şakir; Çapkın, Kadir; Yağcı, Abdulkadir; Cesur, Mehmet; Bilgin, Fuat; Bulut, Cafer; Uysal, Rahmi; Obertegger, Ulrike; Boscaini, Adriano; Flaim, Giovanna; Salmaso, Nico; Cerasino, Leonardo; Richardson, Jessica; Visser, Petra M.; Verspagen, Jolanda M. H.; Karan, Tünay; Soylu, Elif Neyran; Maraşlıoğlu, Faruk; Napiórkowska-Krzebietke, Agnieszka; Ochocka, Agnieszka; Pasztaleniec, Agnieszka; Antão-Geraldes, Ana M.; Vasconcelos, Vitor; Morais, João; Vale, Micaela; Köker, Latife; Akçaalan, Reyhan; Albay, Meriç; Špoljarić Maronić, Dubravka; Stević, Filip; Žuna Pfeiffer, Tanja; Fonvielle, Jeremy; Straile, Dietmar; Rothhaupt, Karl-Otto; Hansson, Lars-Anders; Urrutia-Cordero, Pablo; Bláha, Luděk; Geriš, Rodan; Fránková, Markéta; Koçer, Mehmet Ali Turan; Alp, Mehmet Tahir; Remec-Rekar, Spela; Elersek, Tina; Triantis, Theodoros; Zervou, Sevasti-Kiriaki; Hiskia, Anastasia; Haande, Sigrid; Skjelbred, Birger; Madrecka, Beata; Nemova, Hana; Drastichova, Iveta; Chomova, Lucia; Edwards, Christine; Sevindik, Tuğba Ongun; Tunca, Hatice; Önem, Burçin; Aleksovski, Boris; Krstić, Svetislav; Vucelić, Itana Bokan; Nawrocka, Lidia; Salmi, Pauliina; Machado-Vieira, Danielle; de Oliveira, Alinne Gurjão; Delgado-Martín, Jordi; García, David; Cereijo, Jose Luís; Gomà, Joan; Trapote, Mari Carmen; Vegas-Vilarrúbia, Teresa; Obrador, Biel; Grabowska, Magdalena; Karpowicz, Maciej; Chmura, Damian; Úbeda, Bárbara; Gálvez, José Ángel; Özen, Arda; Christoffersen, Kirsten Seestern; Warming, Trine Perlt; Kobos, Justyna; Mazur-Marzec, Hanna; Pérez-Martínez, Carmen; Ramos-Rodríguez, Eloísa; Arvola, Lauri; Alcaraz-Párraga, Pablo; Toporowska, Magdalena; Pawlik-Skowronska, Barbara; Niedźwiecki, Michał; Pęczuła, Wojciech; Leira, Manel; Hernández, Armand; Moreno-Ostos, Enrique; Blanco, José María; Rodríguez, Valeriano; Montes-Pérez, Jorge Juan; Palomino, Roberto L.; Rodríguez-Pérez, Estela; Carballeira, Rafael; Camacho, Antonio; Picazo, Antonio; Rochera, Carlos; Santamans, Anna C.; Ferriol, Carmen; Romo, Susana; Soria, Juan Miguel; Dunalska, Julita; Sieńska, Justyna; Szymański, Daniel; Kruk, Marek; Kostrzewska-Szlakowska, Iwona; Jasser, Iwona; Žutinić, Petar; Gligora Udovič, Marija; Plenković-Moraj, Anđelka; Frąk, Magdalena; Bańkowska-Sobczak, Agnieszka; Wasilewicz, Michał; Özkan, Korhan; Maliaka, Valentini; Kangro, Kersti; Grossart, Hans-Peter; Paerl, Hans W.; Carey, Cayelan C.; Ibelings, Bas W.

    2018-04-13

    Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.

  4. Botulinum toxin for treatment of glandular hypersecretory disorders.

    LENUS (Irish Health Repository)

    Laing, T A

    2012-02-03

    SUMMARY: The use of botulinum toxin to treat disorders of the salivary glands is increasing in popularity in recent years. Recent reports of the use of botulinum toxin in glandular hypersecretion suggest overall favourable results with minimal side-effects. However, few randomised clinical trials means that data are limited with respect to candidate suitability, treatment dosages, frequency and duration of treatment. We report a selection of such cases from our own department managed with botulinum toxin and review the current data on use of the toxin to treat salivary gland disorders such as Frey\\'s syndrome, excessive salivation (sialorrhoea), focal and general hyperhidrosis, excessive lacrimation and chronic rhinitis.

  5. Gene therapy for carcinoma of the breast: Genetic toxins

    International Nuclear Information System (INIS)

    Vassaux, Georges; Lemoine, Nick R

    2000-01-01

    Gene therapy was initially envisaged as a potential treatment for genetically inherited, monogenic disorders. The applications of gene therapy have now become wider, however, and include cardiovascular diseases, vaccination and cancers in which conventional therapies have failed. With regard to oncology, various gene therapy approaches have been developed. Among them, the use of genetic toxins to kill cancer cells selectively is emerging. Two different types of genetic toxins have been developed so far: the metabolic toxins and the dominant-negative class of toxins. This review describes these two different approaches, and discusses their potential applications in cancer gene therapy

  6. Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

    Directory of Open Access Journals (Sweden)

    Evanthia Mantzouki

    2018-04-01

    Full Text Available Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins. Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a and cytotoxins (e.g., cylindrospermopsin due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.

  7. Dysport: pharmacological properties and factors that influence toxin action.

    Science.gov (United States)

    Pickett, Andy

    2009-10-01

    The pharmacological properties of Dysport that influence toxin action are reviewed and compared with other botulinum toxin products. In particular, the subject of diffusion is examined and discussed based upon the evidence that currently exists, both from laboratory studies and from clinical data. Diffusion of botulinum toxin products is not related to the size of the toxin complex in the product since the complex dissociates under physiological conditions, releasing the naked neurotoxin to act. The active neurotoxin in Type A products is the same and therefore diffusion is equal when equal doses are administered.

  8. Enteric neurons show a primary cilium.

    Science.gov (United States)

    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.

  9. Combined Effect Of Botulinum Toxin And Splinting On Motor Components And Function Of People With Stroke

    Directory of Open Access Journals (Sweden)

    Aryan Shamili

    2017-02-01

    Full Text Available Background and objective: Spasticity is one of the problems following stroke. Due to this increase in muscle tone, patients are confronted to problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of Simultaneous use of both splint and botulinum toxin-A (BTX-A injection on spasticity, range of motion and upper extremity function in a 3-month period. Methods: The design of this study was a comparison between 3 groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about 3 months and the evaluations were done monthly. Goniometry was the method to measure range of motion, and Modified Ashworth scale was used to examine the spasticity and the upper extremity function was scored based on Fugl-Meyer assessment.   Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times.  Significance was set at 0.05. Results: All outcome measures improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month (p> 0 / 05. The results also showed that the changes in elbow`s spasticity {p= 0.05} and wrist`s spasticity {p= 0.007} and upper extremity function { p = 0.04} were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin and splint was more than other groups. Conclusion: In this

  10. Emergence of Escherichia coli encoding Shiga toxin 2f in human Shiga toxin-producing E-coli (STEC) infections in the Netherlands, January 2008 to December 2011

    NARCIS (Netherlands)

    Friesema, I.; van der Zwaluw, K.; Schuurman, T.; Kooistra-Smid, M.; Franz, E.; van Duynhoven, Y.; van Pelt, W.

    2014-01-01

    The Shiga toxins of Shiga toxin-producing Escherichia coli (STEC) can be divided into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) with several sub-variants. Variant Stx(2f) is one of the latest described, but has been rarely associated with symptomatic human infections. In the enhanced STEC

  11. Siderophore-based immunization strategy to inhibit growth of enteric pathogens.

    Science.gov (United States)

    Sassone-Corsi, Martina; Chairatana, Phoom; Zheng, Tengfei; Perez-Lopez, Araceli; Edwards, Robert A; George, Michael D; Nolan, Elizabeth M; Raffatellu, Manuela

    2016-11-22

    Infections with Gram-negative pathogens pose a serious threat to public health. This scenario is exacerbated by increases in antibiotic resistance and the limited availability of vaccines and therapeutic tools to combat these infections. Here, we report an immunization approach that targets siderophores, which are small molecules exported by enteric Gram-negative pathogens to acquire iron, an essential nutrient, in the host. Because siderophores are nonimmunogenic, we designed and synthesized conjugates of a native siderophore and the immunogenic carrier protein cholera toxin subunit B (CTB). Mice immunized with the CTB-siderophore conjugate developed anti-siderophore antibodies in the gut mucosa, and when mice were infected with the enteric pathogen Salmonella, they exhibited reduced intestinal colonization and reduced systemic dissemination of the pathogen. Moreover, analysis of the gut microbiota revealed that reduction of Salmonella colonization in the inflamed gut was accompanied by expansion of Lactobacillus spp., which are beneficial commensal organisms that thrive in similar locales as Enterobacteriaceae. Collectively, our results demonstrate that anti-siderophore antibodies inhibit Salmonella colonization. Because siderophore-mediated iron acquisition is a virulence trait shared by many bacterial and fungal pathogens, blocking microbial iron acquisition by siderophore-based immunization or other siderophore-targeted approaches may represent a novel strategy to prevent and ameliorate a broad range of infections.

  12. Toxinas de Clostridium perfringens Toxins of Clostridium perfringens

    Directory of Open Access Journals (Sweden)

    W. E. Morris

    2009-12-01

    Full Text Available Clostridium perfringens es un bacilo grampositivo anaerobio con capacidad de formar esporas. Es uno de los patógenos bacterianos con mayor distribución en el medio ambiente, ya que puede ser aislado de muestras de suelo y de agua y además forma parte de la microbiota intestinal de animales y humanos. Sin embargo, en ciertas ocasiones puede actuar como patógeno oportunista y causar enfermedades como la gangrena gaseosa, la enterotoxemia del ovino y del caprino y la disentería del cordero, entre otras. En humanos, está asociado a enfermedades como la intoxicación por alimentos, la enterocolitis necrotizante en niños y la enteritis necrótica o pigbel de las tribus de Papúa-Nueva Guinea. El renovado interés que existe actualmente en el estudio de C. perfringens como patógeno veterinario y humano, junto con el avance de la biología molecular, han hecho posible que la ciencia tenga hoy un conocimiento más profundo sobre la biología y la patogenia de esta bacteria. En esta revisión bibliográfica se discuten y actualizan los principales aspectos de la patogenia intestinal de C. perfringens teniendo en cuenta las toxinas con mayor importancia médica descritas hasta el presente.Clostridium perfringens is an anaerobic gram-positive spore-forming bacillus. It is one of the pathogens with larger distribution in the environment; it can be isolated from soil and water samples, which also belongs to the intestinal flora of animals and humans. However, on some occasions it can act as an opportunistic pathogen, causing diseases such as gas gangrene, enterotoxemia in sheep and goats and lamb dysentery, among others. In human beings, it is associated to diseases such as food poisoning, necrotic enterocolitis of the infant and necrotic enteritis or pigbel in Papua-New Guinea tribes. The renewed interest existing nowadays in the study of C. perfringens as a veterinarian and human pathogen, together with the advance of molecular biology, had enabled

  13. Genomic diversification of giant enteric symbionts reflects host dietary lifestyles

    KAUST Repository

    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

  14. Botulinum toxin for treatment of restrictive strabismus.

    Science.gov (United States)

    Merino, Pilar S; Vera, Rebeca E; Mariñas, Laura G; Gómez de Liaño, Pilar S; Escribano, Jose V

    To study the types of acquired restrictive strabismus treated in a tertiary hospital and the outcome of treatment with botulinum toxin. We performed a 10-year retrospective study of patients with restrictive strabismus aged ≥18 years who were treated with botulinum toxin. Treatment was considered successful if the final vertical deviation was ≤5 PD, horizontal deviation ≤10 PD, with no head turn or diplopia. We included 27 cases (mean age, 61.9 years). Horizontal strabismus was diagnosed in 11.1%, vertical in 51.9%, and mixed in 37%. Strabismus was secondary to cataract surgery in 6 cases, high myopia in 6, orbital fractures in 5, retinal surgery in 5, Graves ophthalmopathy in 4, and repair of conjunctival injury in 1 case. Diplopia was diagnosed in all patients, head turn in 33.3%. The initial deviation was 14 PD (range, 2-40), the mean number of injections per patient was 1.6 (range, 1-3), and the mean dose was 9.5 IU (range, 2.5-22.5). At the end of follow-up, diplopia was recorded in 59.3%, head turn in 18.5%, surgical treatment in 51.9%, and need for prism glasses in 14.8%. Outcome was successful in 37% of patients (4 high myopia, 3 orbital fractures, 2 post-surgical retinal detachment, and 1 post-cataract surgery). Mean follow-up was 3±1.8 years. Vertical deviation was observed in half of the sample. The most frequent deviation was secondary to cataract surgery and high myopia. Treatment with botulinum toxin was successful in one-third of the patients at the end of follow-up. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  15. Ultrasound-guided botulinum toxin injections

    Directory of Open Access Journals (Sweden)

    S. E. Khatkova

    2016-01-01

    Full Text Available One of the key conditions for achieving the desirable result during botulinum toxin therapy for muscular dystonia, spasticity, and other diseases accompanied by spasm, pain, and autonomic dysfunction (dystonias, spasticity, etc. is the proper administration of the agent into the muscles directly involved in the pathological process. The exact entry of botulinum toxin into the target muscles is essential for successful and safe treatment because its injection into a normal muscle may cause side effects. The most common errors are the incorrect depth and incorrect direction of a needle on insertion. Therefore, the exact injection of the agent particularly into the shallow and deep muscles is a difficult task even for an experienced specialist and requires the use of controlling methods.The European Consensus on Botulinum Toxin Therapy points out that various injection techniques are needed for the better identification of necessary muscles. However, there are currently no reports on the clear advantage of any technique. In our country, injections using palpation and anatomical landmarks have been widely used in routine practice so far; electromyographic monitoring and electrostimulation have been less frequently applied. In recent years, the new method ultrasound-guided injection has continued to grow more popular. This effective, accessible, and easy-to-use method makes it possible to manage a real-time injection process and to ensure the exact entry of the agent into the muscle. This paper is dedicated to a comparative analysis of different injection methods and to a description of the ultrasound-guided technique and its advantages over others. 

  16. Prevention, control and detection of Fusarial toxins

    Directory of Open Access Journals (Sweden)

    Nešić Ksenija D.

    2013-01-01

    Full Text Available The past couple of decades have provided considerable details on fungi and the toxins that they produce, as well on the mechanism of toxin action, toxicity and effects on animal and human health. But, since they are natural contaminants, their presence is often inevitable. Fusaria are widespread in all cereal-growing territories of the world, but they are especially common in our geographic area. Therefore, special attention is paid to the prevention and control, and also to the improvement of methods for their detection. Although all collected data were critical for understanding this worldwide problem, managing the impact of these toxins on the feed and food safety is still great practical challenge. There are a number of approaches that can be taken to minimize mycotoxin contamination in this chain: prevention of fungal growth and thus mycotoxin formation, strategies to reduce or eliminate mycotoxins from contaminated feedstuffs or diverting the contaminated products to low risk uses. A control program for mycotoxins from field to table should in­volve the criteria of an HACCP (Hazard Analysis Critical Control Points approach. It requires an understanding of the important aspects of the interactions of the toxigenic fungi with crop plants, the on-farm production and harvest methods for crops, the production of livestock using grains and processed feeds, including diagnostic capabilities for mycotoxicoses, and all the way to the development of processed foods for human consumption, as well as understanding the marketing and trade channels including storage and delivery of foods to the consumer’s table. A good testing protocol for mycotoxins is necessary to manage all of the control points and in order to be able to ensure a food supply free of toxic levels of mycotoxins for the consumer. [Projekat Ministarstva nauke Republike Srbije, br. III 46009

  17. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    Science.gov (United States)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-04-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  18. Uptake and bioaccumulation of Cry toxins by an aphidophagous predator

    International Nuclear Information System (INIS)

    Paula, Débora P.; Andow, David A.

    2016-01-01

    Uptake of Cry toxins by insect natural enemies has rarely been considered and bioaccumulation has not yet been demonstrated. Uptake can be demonstrated by the continued presence of Cry toxin after exposure has stopped and gut contents eliminated. Bioaccumulation can be demonstrated by showing uptake and that the concentration of Cry toxin in the natural enemy exceeds that in its food. We exposed larvae of the aphidophagous predator, Harmonia axyridis, to Cry1Ac and Cry1F through uniform and constant tritrophic exposure via an aphid, Myzus persicae, and looked for toxin presence in the pupae. We repeated the experiment using only Cry1F and tested newly emerged adults. Both Cry toxins were detected in pupae, and Cry1F was detected in recently emerged, unfed adults. Cry1Ac was present 2.05 times and Cry1F 3.09 times higher in predator pupae than in the aphid prey. Uptake and bioaccumulation in the third trophic level might increase the persistence of Cry toxins in the food web and mediate new exposure routes to natural enemies. - Highlights: • Uptake and bioaccumulation of two Cry toxins by a larval coccinellid was tested. • Uptake was demonstrated by presence of the toxins in pupae and adults. • Bioaccumulation was shown by higher toxin concentration in pupae than prey. • Cry1Ac was present 2.05× and Cry1F 3.09× higher in predator pupae than prey. • This might increase persistence of Cry toxins in food webs with new exposure routes. - Immatures of the predaceous coccinellid Harmonia axyridis can uptake and bioaccumulate Cry toxins delivered via their aphid prey.

  19. Gastric emptying of enteric-coated tablets

    International Nuclear Information System (INIS)

    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

  20. Russian Gas Market: Entering New Era

    International Nuclear Information System (INIS)

    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

  1. Enteric methane emissions from German dairy cows

    DEFF Research Database (Denmark)

    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...

  2. Radiation enteritis. Evaluation of surgical cases

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Optimal Time to Enter a Retirement Village

    Directory of Open Access Journals (Sweden)

    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.

  4. APOLLO 10 ASTRONAUT ENTERS LUNAR MODULE SIMULATOR

    Science.gov (United States)

    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.

  5. Reactive Arthritis Caused by Yersinia enterocolitica Enteritis.

    Science.gov (United States)

    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.

  6. Compounded Apixaban Suspensions for Enteral Feeding Tubes.

    Science.gov (United States)

    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.

  7. Enteral Feeding in Abdominal Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    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

  8. Early enteral nutrition compared to outcome in critically ill trauma ...

    African Journals Online (AJOL)

    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 ...

  9. 30 CFR 77.1502 - Auger holes; restriction against entering.

    Science.gov (United States)

    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...

  10. Isolation of Shiga toxin-producing Escherichia coli harboring variant Shiga toxin genes from seafood

    Directory of Open Access Journals (Sweden)

    Sreepriya Prakasan

    2018-03-01

    Full Text Available Background and Aim: Shiga toxin-producing Escherichia coli (STEC are important pathogens of global significance. STEC are responsible for numerous food-borne outbreaks worldwide and their presence in food is a potential health hazard. The objective of the present study was to determine the incidence of STEC in fresh seafood in Mumbai, India, and to characterize STEC with respect to their virulence determinants. Materials and Methods: A total of 368 E. coli were isolated from 39 fresh seafood samples (18 finfish and 21 shellfish using culture-based methods. The isolates were screened by polymerase chain reaction (PCR for the genes commonly associated with STEC. The variant Shiga toxin genes were confirmed by Southern blotting and hybridization followed by DNA sequencing. Results: One or more Shiga toxins genes were detected in 61 isolates. Of 39 samples analyzed, 10 (25.64% samples harbored STEC. Other virulence genes, namely, eaeA (coding for an intimin and hlyA (hemolysin A were detected in 43 and 15 seafood isolates, respectively. The variant stx1 genes from 6 isolates were sequenced, five of which were found to be stx1d variants, while one sequence varied considerably from known stx1 sequences. Southern hybridization and DNA sequence analysis suggested putative Shiga toxin variant genes (stx2 in at least 3 other isolates. Conclusion: The results of this study showed the occurrence of STEC in seafood harboring one or more Shiga toxin genes. The detection of STEC by PCR may be hampered due to the presence of variant genes such as the stx1d in STEC. This is the first report of stx1d gene in STEC isolated from Indian seafood.

  11. 76 FR 78215 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review; Proposed Rule

    Science.gov (United States)

    2011-12-16

    ... agents and toxins list; whether minimum standards for personnel reliability, physical and cyber security... toxins list; (3) whether minimum standards for personnel reliability, physical and cyber security should...

  12. Shiga Toxin (Stx) Gene Detection and Verotoxigenic Potentials of ...

    African Journals Online (AJOL)

    DR-AMADI

    Nigerian Journal of Basic and Applied Science (June, 2016), 24(1): 98-105 .... dangerous pathogenic shiga- toxin producing E. coli from the food product. Consequent .... Table 3: Vero Toxin Analysis of non – 0157 E. coli Isolates From Nono Sold in Nigeria. City .... receptors in their plasma membranes and will detect all ...

  13. EFFECT OF MARINE TOXINS ON THERMOREGULATION IN MICE.

    Science.gov (United States)

    Marine algal toxins are extremely toxic and can represent a major health problem to humans and animals. Temperature regulation is one of many processes to be affected by exposure to these toxins. Mice and rats become markedly hypothermic when subjected to acute exposure to the ma...

  14. Oxidative Stress in Shiga Toxin Production by Enterohemorrhagic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Katarzyna Licznerska

    2016-01-01

    Full Text Available Virulence of enterohemorrhagic Escherichia coli (EHEC strains depends on production of Shiga toxins. These toxins are encoded in genomes of lambdoid bacteriophages (Shiga toxin-converting phages, present in EHEC cells as prophages. The genes coding for Shiga toxins are silent in lysogenic bacteria, and prophage induction is necessary for their efficient expression and toxin production. Under laboratory conditions, treatment with UV light or antibiotics interfering with DNA replication are commonly used to induce lambdoid prophages. Since such conditions are unlikely to occur in human intestine, various research groups searched for other factors or agents that might induce Shiga toxin-converting prophages. Among other conditions, it was reported that treatment with H2O2 caused induction of these prophages, though with efficiency significantly lower relative to UV-irradiation or mitomycin C treatment. A molecular mechanism of this phenomenon has been proposed. It appears that the oxidative stress represents natural conditions provoking induction of Shiga toxin-converting prophages as a consequence of H2O2 excretion by either neutrophils in infected humans or protist predators outside human body. Finally, the recently proposed biological role of Shiga toxin production is described in this paper, and the “bacterial altruism” and “Trojan Horse” hypotheses, which are connected to the oxidative stress, are discussed.

  15. Short Toxin-like Proteins Abound in Cnidaria Genomes

    Directory of Open Access Journals (Sweden)

    Michal Linial

    2012-11-01

    Full Text Available Cnidaria is a rich phylum that includes thousands of marine species. In this study, we focused on Anthozoa and Hydrozoa that are represented by the Nematostella vectensis (Sea anemone and Hydra magnipapillata genomes. We present a method for ranking the toxin-like candidates from complete proteomes of Cnidaria. Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. Fundamental features that were emphasized in training ClanTox include cysteines and their spacing along the sequences. Among the 83,000 proteins derived from Cnidaria representatives, we found 170 candidates that fulfill the properties of toxin-like-proteins, the vast majority of which were previously unrecognized as toxins. An additional 394 short proteins exhibit characteristics of toxin-like proteins at a moderate degree of confidence. Remarkably, only 11% of the predicted toxin-like proteins were previously classified as toxins. Based on our prediction methodology and manual annotation, we inferred functions for over 400 of these proteins. Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of the proteins belong to small families of paralogs. We conclude that the evolutionary expansion of toxin-like proteins in Cnidaria contributes to their fitness in the complex environment of the aquatic ecosystem.

  16. Physiological effect of the toxin from Xanthomonas retroflexus on ...

    African Journals Online (AJOL)

    Physiological effect of the toxin from Xanthomonas retroflexus on redroot pigweed (Amaranthus retroflexus). Z Sun, M Li, J Chen, Y Li. Abstract. A new toxin from Xanthomonas retroflexus could cause a series of physiological responses on seedlings of redroot pigweed. The experimental results revealed that respiratory ratio ...

  17. Treatment of anismus in intractable constipation with botulinum A toxin.

    Science.gov (United States)

    Hallan, R I; Williams, N S; Melling, J; Waldron, D J; Womack, N R; Morrison, J F

    1988-09-24

    In seven patients with anismus the striated sphincter muscle complex was selectively weakened by local injection of Clostridium botulinum type A toxin. Symptom scores improved significantly and correlated with a significant reduction in the maximum voluntary and canal squeeze pressure and a significant increase in the anorectal angle on straining. Botulinum A toxin seems to be promising treatment for some patients with anismus.

  18. T-2 toxin Analysis in Poultry and Cattle Feedstuff.

    Science.gov (United States)

    Gholampour Azizi, Issa; Azarmi, Masumeh; Danesh Pouya, Naser; Rouhi, Samaneh

    2014-05-01

    T-2 toxin is a mycotoxin that is produced by the Fusarium fungi. Consumption of food and feed contaminated with T-2 toxin causes diseases in humans and animals. In this study T-2 toxin was analyzed in poultry and cattle feedstuff in cities of Mazandaran province (Babol, Sari, Chalus), Northern Iran. In this study, 90 samples were analyzed for T-2 toxin contamination by the ELISA method. Out of 60 concentrate and bagasse samples collected from various cities of Mazandaran province, 11.7% and 3.3% were contaminated with T-2 toxin at concentrations > 25 and 50 µg/kg, respectively. For mixed poultry diets, while 10% of the 30 analyzed samples were contaminated with > 25 µg/kg, none of the tested samples contained T-2 toxin at levels > 50 µg/kg. The results obtained from this study show that poultry and cattle feedstuff can be contaminated with different amounts of T-2 toxin in different conditions and locations. Feedstuff that are contaminated by this toxin cause different diseases in animals; thus, potential transfer of mycotoxins to edible by-products from animals fed mycotoxin-contaminated feeds drives the need to routinely monitor mycotoxins in animal feeds and their components. This is the basis on which effective management of mycotoxins and their effects can be implemented.

  19. Retrograde transport of protein toxins through the Golgi apparatus

    DEFF Research Database (Denmark)

    Sandvig, Kirsten; Skotland, Tore; van Deurs, Bo

    2013-01-01

    at the cell surface, and they are endocytosed both by clathrin-dependent and clathrin-independent mechanisms. Sorting to the Golgi and retrograde transport to the endoplasmic reticulum (ER) are common to these toxins, but the exact mechanisms turn out to be toxin and cell-type dependent. In the ER...

  20. Short inventory of EU legislation on plant toxins in food

    NARCIS (Netherlands)

    Nijs, de M.; Noordam, M.Y.; Mol, H.G.J.

    2017-01-01

    Plant toxins, secondary metabolites that are not essential for the survival of the organism itself but are toxic to human health, are produced by many plants. Plant toxins can be present as inherent metabolites in daily foods such as potatoes, herbs and spices or in herbal preparations. Plant

  1. 9 CFR 121.3 - VS select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

  2. Solid-phase synthesis of polyamine toxin analogues

    DEFF Research Database (Denmark)

    Kromann, Hasse; Krikstolaityte, Sonata; Andersen, Anne J

    2002-01-01

    The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate re...

  3. Guidelines for safe handling of toxins. Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Szilagyi, M.

    1995-11-01

    Toxins are highly toxic chemicals which cause illness through all routes of entry into the body. This technical note has been prepared to ensure that preparation, handling, and disposal of toxins does not constitute a greater occupational hazard than is necessary. It includes hazards that may be encountered and the precautions that should be taken against such hazards.

  4. Recent advances in the medicinal chemistry of polyamine toxins

    DEFF Research Database (Denmark)

    Strømgaard, K; Andersen, K; Krogsgaard-Larsen, P

    2001-01-01

    This review describes the recent developments in the field of polyamine toxins, with focus on structure activity relationship investigations, including studies of importance of the polyamine moiety for biological activity, photolabeling studies using polyamine toxins as templates, as well as use ...

  5. The resurgence of botulinum toxin injection for strabismus in children.

    Science.gov (United States)

    Mahan, Marielle; Engel, J Mark

    2017-09-01

    The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.

  6. Effect of Cryphonectria parasitica toxin on lipid peroxidation and ...

    African Journals Online (AJOL)

    In order to clarify the responses of different chestnut cultivars to Cp-toxin stress, the effect of Cp-toxin from Cryphonectria parasitica (Murr.) Barr on Castanea mollissima Blume, especially on its cell structure, was examined. Chestnut shoots of both resistant (Beiyu No. 2) and susceptible (Hongguang) cultivars were treated ...

  7. Enhanced sporulation and toxin production by a mutant derivative of ...

    African Journals Online (AJOL)

    fatima

    total proteins determined with the toxin producing organism. All values are the ... synthesis specific yield was the ratio of δ-endo-toxin (mg L-1) divided by .... corresponding to 31.8 mg. 108 spore. −1 delta-endotoxins, it became apparent that ...

  8. The Biochemical Toxin Arsenal from Ant Venoms

    Directory of Open Access Journals (Sweden)

    Axel Touchard

    2016-01-01

    Full Text Available Ants (Formicidae represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents.

  9. Cardiovascular-Active Venom Toxins: An Overview.

    Science.gov (United States)

    Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

    2016-01-01

    Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.

  10. The Biochemical Toxin Arsenal from Ant Venoms

    Science.gov (United States)

    Touchard, Axel; Aili, Samira R.; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M.; Dejean, Alain

    2016-01-01

    Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID:26805882

  11. Lactobacillus bulgaricus mutants decompose uremic toxins.

    Science.gov (United States)

    Bai, Yun-Huan; Jiang, Ya-Fen; Jiang, Yun-Sheng

    2014-06-01

    We aim to obtain a probiotic strain from Lactobacillus bulgaricus by testing its capability to decompose uremic toxins to provide new intestinal bacteria for the treatment of chronic renal failure. Original L. bulgaricus was cultured with the serum of uremic patients and then mutated by physical (ultraviolet) and chemical (diethyl sulfate) methods repeatedly. Using creatinine decomposition rate as an observed index, we selected the best strains which decreased the most concentration of the creatinine. We then tested its ability to decompose urea, uric acid, serum phosphate, parathyroid hormone, and homocysteine and its genetic stability. After inductive and mutagenic treatment, DUC3-17 was selected. Its decomposition rate of creatinine, urea nitrogen, uric acid, phosphorus, parathyroid hormone, and homocysteine were 17.23%, 36.02%, 9.84%, 15.73%, 78.26%, and 12.69%, respectively. The degrading capacity was sustained over five generations. After directional induction and compound mutation, L. bulgaricus has greater capacity to decompose uremic toxins, with a stable inheritance.

  12. [Botulinum toxin and rejuvenation of the eye].

    Science.gov (United States)

    Volpei, Ch; Miniconi, M-J; Brunner, C I; Besins, T; Braccini, F

    2013-01-01

    Treatments with botulinum toxin in the forehead and periorbital areas may induce disappointing or even paradoxical results. Our study, focused on this area aimed at refining injection techniques by analyzing muscular balances and comparing the effect according to injection doses and topography. This experimental study has been carried out in the form of 2 session workshops, with volunteers duly informed of the study contents and giving their informed consent. It was conducted by physicians and surgeons members of SAMCEP* (Société Avancée de Médecine et Chirurgie Esthétique et Plastique). The botulinum toxin was onabotulinumtoxin A. Results were evaluated 15 days after treatment, in regard to global eyebrow position, eyebrow head and tail position; muscle interactions; lines above the eyebrow. Eleven case reports and their results are shown and discussed. Our study underlines two important insights: muscle balances and "border areas", between orbicularis oculi and corrugator, key features for eyebrow head, and between frontalis and orbicularis oculifor eyebrow tail.

  13. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

    International Nuclear Information System (INIS)

    Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

    1986-01-01

    Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release

  14. Milling technological experiments to reduce Fusarium toxin contamination in wheat

    Directory of Open Access Journals (Sweden)

    Véha A.

    2015-01-01

    Full Text Available We examine 4 different DON-toxin-containing (0.74 - 1.15 - 1.19 - 2.14 mg/kg winter wheat samples: they were debranned and undebranned, and we investigated the flour’s and the by-products’ (coarse, fine bran toxin content changes. SATAKE lab-debranner was used for debranning and BRABENDER lab-mill for the milling process. Without debranning, two sample flours were above the DON toxin limit (0.75 mg/kg, which are waste. By minimum debranning (and minimum debranning mass loss; 6-8%, our experience with whole flour is that the multi-stage debranning measurement significantly reduces the content of the flour’s DON toxin, while the milling by-products, only after careful consideration and DON toxin measurements, may be produced for public consumption and for feeding.

  15. Botulinum toxin in the treatment of vocal fold nodules.

    Science.gov (United States)

    Allen, Jacqui E; Belafsky, Peter C

    2009-12-01

    Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

  16. Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A

    Directory of Open Access Journals (Sweden)

    Giuseppe Brisinda

    2015-05-01

    Full Text Available Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract.

  17. Proteomic profiling of Mycobacterium tuberculosis identifies nutrient-starvation-responsive toxin-antitoxin systems

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Agner, Jeppe; Piersma, Sander R

    2013-01-01

    In order to successfully enter the latent stage, Mycobacterium tuberculosis must adapt to conditions such as nutrient limitation and hypoxia. In vitro models that mimic latent infection are valuable tools for describing the changes in metabolism that occur when the bacterium exists in a non......-growing form. We used two complementary proteomic approaches, label-free LC-MS/MS analysis and two-dimensional difference gel electrophoresis, to determine the proteome profile of extracellular proteins from M. tuberculosis cultured under nutrient starvation. Through the label-free LC-MS/MS analysis......, significant differences in the overall metabolism during nutrient starvation were detected. Notably, members of the toxin-antitoxin systems were present in larger quantities in nutrient-starved cultures, supporting a role for these global modules as M. tuberculosis switches its metabolism into dormancy...

  18. Intrinsic Toxin-Derived Peptides Destabilize and Inactivate Clostridium difficile TcdB

    Directory of Open Access Journals (Sweden)

    Jason L. Larabee

    2017-05-01

    Full Text Available Clostridium difficile infection (CDI is a major cause of hospital-associated, antibiotic-induced diarrhea, which is largely mediated by the production of two large multidomain clostridial toxins, TcdA and TcdB. Both toxins coordinate the action of specific domains to bind receptors, enter cells, and deliver a catalytic fragment into the cytosol. This results in GTPase inactivation, actin disassembly, and cytotoxicity. TcdB in particular has been shown to encode a region covering amino acids 1753 to 1851 that affects epitope exposure and cytotoxicity. Surprisingly, studies here show that several peptides derived from this region, which share the consensus sequence 1769NVFKGNTISDK1779, protect cells from the action of TcdB. One peptide, PepB2, forms multiple interactions with the carboxy-terminal region of TcdB, destabilizes TcdB structure, and disrupts cell binding. We further show that these effects require PepB2 to form a higher-order polymeric complex, a process that requires the central GN amino acid pair. These data suggest that TcdB1769–1779 interacts with repeat sequences in the proximal carboxy-terminal domain of TcdB (i.e., the CROP domain to alter the conformation of TcdB. Furthermore, these studies provide insights into TcdB structure and functions that can be exploited to inactivate this critical virulence factor and ameliorate the course of CDI.

  19. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    Science.gov (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  20. Measurement and prediction of enteric methane emission

    Science.gov (United States)

    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

  1. [Enteral nutrition: reduction in the contamination risk].

    Science.gov (United States)

    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

  2. Enter as an outsider: Teaching organizational humility.

    Science.gov (United States)

    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.

  3. Treatment of radiation enteritis: a comparison study

    International Nuclear Information System (INIS)

    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

  4. Pathophysiology and surgical treatment for radiation enteritis

    International Nuclear Information System (INIS)

    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)

  5. Pathophysiology and surgical treatment for radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    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).

  6. Enteral Nutrition in Pancreaticoduodenectomy: A Literature Review

    Directory of Open Access Journals (Sweden)

    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.

  7. Chronic radiation enteritis: A community hospital experience

    International Nuclear Information System (INIS)

    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

  8. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree and developed an algorithm (SpiderP for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html, a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from

  9. Osmolality and pH in handmade enteral diets used in domiciliary enteral nutritional therapy

    Directory of Open Access Journals (Sweden)

    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.

  10. Botulinum toxin injection in laryngeal dyspnea.

    Science.gov (United States)

    Woisard, Virginie; Liu, Xuelai; Bes, Marie Christine Arné; Simonetta-Moreau, Marion

    2017-02-01

    Data, regarding the use of botulinum toxin (BT-A) in laryngeal dyspnea, are scarce, coming from some cases reports in the literature, including Vocal fold paralysis, laryngeal dystonia, vocal cord dysfunction also called paradoxical motion of the vocal fold (PMVF), and post-neuroleptic laryngeal dyskinesia. There is no consensus regarding the muscles and the doses to inject. The aim of this study is to present a retrospective review of patients treated in our ENT Department by BT-A injection in this indication. This study is a retrospective study describing patients who underwent an injection of botulinum toxin for laryngeal dyspnea in the ENT Department from 2005 to 2015 years. The inclusion criteria were a dyspnea associated with a laryngeal dysfunction, confirmed by flexible fiberoptic nasopharyngolaryngoscopy. Information concerning the causes of the dyspnea, the botulinum toxin BT-A injections procedure, post-injection follow-up, and respiratory outcome were collected for all patients included. In the group of 13 patients included, the main cause identified as principal factor linked with the short breath was: a bilateral VF paralysis (Patel et al., Otolaryngol Head Neck Surg 130:686-689, 7), laryngeal dystonia (Balkissoon and Kenn, Semin Respir Crit Care Med 33:595-605, 2), Anxiety syndrome associated with unilateral vocal fold paralysis or asthma (Marcinow et al., Laryngoscope 124:1425-1430, 3), and an isolated asthma (Zwirner et al., Eur Arch Otorhinolaryngol 254:242-245, 1). Nine out of the thirteen patients were improved by the injections. A BT-A-induced stable benefit for four patients led them to stop the injections in the follow-up. Good outcome was observed in five other patients (main cause: bilateral VP paralysis), allowing a progressive lengthening of the delay between BT-A injections. Four patients did not report a positive risk/benefit ratio after BT-A injections; two of them (with bilateral VF paralysis), because of respiratory side effects and

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

    Science.gov (United States)

    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.

  12. Potentiometric chemical sensors for the detection of paralytic shellfish toxins.

    Science.gov (United States)

    Ferreira, Nádia S; Cruz, Marco G N; Gomes, Maria Teresa S R; Rudnitskaya, Alisa

    2018-05-01

    Potentiometric chemical sensors for the detection of paralytic shellfish toxins have been developed. Four toxins typically encountered in Portuguese waters, namely saxitoxin, decarbamoyl saxitoxin, gonyautoxin GTX5 and C1&C2, were selected for the study. A series of miniaturized sensors with solid inner contact and plasticized polyvinylchloride membranes containing ionophores, nine compositions in total, were prepared and their characteristics evaluated. Sensors displayed cross-sensitivity to four studied toxins, i.e. response to several toxins together with low selectivity. High selectivity towards paralytic shellfish toxins was observed in the presence of inorganic cations with selectivity coefficients ranging from 0.04 to 0.001 for Na + and K + and 3.6*10 -4 to 3.4*10 -5 for Ca 2+ . Detection limits were in the range from 0.25 to 0.9 μmolL -1 for saxitoxin and decarbamoyl saxitoxin, and from 0.08 to 1.8 μmolL -1 for GTX5 and C1&C2, which allows toxin detection at the concentration levels corresponding to the legal limits. Characteristics of the developed sensors allow their use in the electronic tongue multisensor system for simultaneous quantification of paralytic shellfish toxins. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Synthesis of protein in intestinal cells exposed to cholera toxin

    International Nuclear Information System (INIS)

    Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

    1987-01-01

    The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells and Chinese hamster ovary cells exposed to cholera toxin. An increase in [ 3 H] leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of [ 35 S] methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed

  14. Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish

    Science.gov (United States)

    Reguera, Beatriz; Riobó, Pilar; Rodríguez, Francisco; Díaz, Patricio A.; Pizarro, Gemita; Paz, Beatriz; Franco, José M.; Blanco, Juan

    2014-01-01

    Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated. PMID:24447996

  15. ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

    Science.gov (United States)

    Baseman, Joel B.; Pappenheimer, A. M.; Gill, D. M.; Harper, Annabel A.

    1970-01-01

    The blood clearance and distribution in the tissues of 125I after intravenous injection of small doses (1.5–5 MLD or 0.08–0.25 µg) of 125I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected 125I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal. PMID:5511567

  16. Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish

    Directory of Open Access Journals (Sweden)

    Beatriz Reguera

    2014-01-01

    Full Text Available Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP, even at low cell densities (<103 cells·L−1. They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins, and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated.

  17. Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

    Science.gov (United States)

    Scobie, Heather M; Wigelsworth, Darran J; Marlett, John M; Thomas, Diane; Rainey, G. Jonah A; Lacy, D. Borden; Manchester, Marianne; Collier, R. John; Young, John A. T

    2006-01-01

    Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis. PMID:17054395

  18. Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications

    Directory of Open Access Journals (Sweden)

    Chew Chieng Yeo

    2016-02-01

    Full Text Available Toxin-antitoxin (TA systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies.

  19. Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications

    Science.gov (United States)

    Yeo, Chew Chieng; Abu Bakar, Fauziah; Chan, Wai Ting; Espinosa, Manuel; Harikrishna, Jennifer Ann

    2016-01-01

    Toxin-antitoxin (TA) systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies. PMID:26907343

  20. Botulinum toxin drugs: brief history and outlook.

    Science.gov (United States)

    Dressler, D

    2016-03-01

    The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

  1. [Applications of botulinum toxin in Neurology].

    Science.gov (United States)

    Garcia-Ruiz, Pedro J

    2013-07-07

    At present, botulinum toxin (BT) is one of the most fundamental available drugs in Neurology, only comparable with levodopa. BT is currently used in those entities characterized by excessive muscle contraction, including dystonia and spasticity. In addition, BT has been used to control pain associated with increased muscle contraction in dystonia and spasticity, but also is useful to control chronic pain not associated with muscle contraction, such as chronic daily headache. Finally, BT is useful in sialorrhoea and bruxism. The mechanism of action is complex, mainly acting on terminal neuromuscular junction, but also exhibiting analgesic properties, probably through inhibition of pain neurotransmitters release. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  2. [Sensory evaluation of enteral nutritional supplements].

    Science.gov (United States)

    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.

  3. Uric Acid: The Unknown Uremic Toxin.

    Science.gov (United States)

    Treviño-Becerra, Alejandro

    2018-01-01

    This review brings together concepts of uric acid metabolism affecting renal parenchyma and its function and the current therapies to reduce hyperuricemia (HyU) and avoid renal disease progression. High uric acid plays an important role in several chronic diseases including kidney diseases such as lithiasis, gout nephropathy, and preeclampsia. In the last 30 years, it has been shown that reducing HyU with low protein and low purine diets in addition to allopurinol creates physiopathological conditions that produce a slight increase in the glomerular filtration rate (GFR). In recent years, in a new era of research in clinical, genetics, pharmacological, and epidemiologic fields, they have been moving forward to support the idea that reduction in HyU could benefit the chronic renal failure (CRF) patients (stage III-IV), thereby avoiding the drop of GFR for undefined mechanisms. There are several clinical trials in progress that show the HyU reducing to very low values and an increased GFR. In a young population, when treating HyU there is a reduction in high blood pressure. There are some reports showing that HyU could play a role in the diabetic nephropathy. Therefore, there have been some speculations that HyU treatment could stop the progression of CRF modifying the natural history of the diseases. So there will be new clinical trials with old and new medication and metabolic procedure to maintain a very low blood levels in the unknown uremic toxin know as uric acid which seems to be the toxin to the damage kidney. © 2018 S. Karger AG, Basel.

  4. Polycystic ovary syndrome and environmental toxins.

    Science.gov (United States)

    Rutkowska, Aleksandra Zofia; Diamanti-Kandarakis, Evanthia

    2016-09-15

    Polycystic ovary syndrome (PCOS) is the most common, heterogeneous, and multifactorial endocrine disorder in premenopausal women. The pathophysiology of this endocrinopathy is still unclear; however, the heterogeneity of its features within ethnic races, geographic location, and families suggests that environment and lifestyle are of prime importance. This work is mainly focused on the possible role of the most common and studied environmental toxins for this syndrome in the pathogenesis of PCOS. Plasticizers, such as bisphenol A (BPA) or phthalates, which belong to the categories of endocrine disrupting chemicals (EDCs) and advanced glycation end products (AGEs), affect humans' health in everyday, industrialized life; therefore special attention should be paid to such exposure. Timing of exposure to EDCs is crucial for the intensity of adverse health effects. It is now evident that fetuses, infants, and/or young children are the most susceptible groups, especially in the early development periods. Prenatal exposure to EDCs that mimic endogenous hormones may contribute to the altered fetal programming and in consequence lead to PCOS and other adverse health effects, potentially transgenerationally. Acute or prolonged exposure to EDCs and AGEs through different life cycle stages may result in destabilization of the hormonal homeostasis and lead to disruption of reproductive functions. They may also interfere with metabolic alterations such as obesity, insulin resistance, and compensatory hyperinsulinemia that can exacerbate the PCOS phenotype and contribute to PCOS consequences such as type 2 diabetes and cardiovascular disease. Since wide exposure to environmental toxins and their role in the pathophysiology of PCOS are supported by extensive data derived from diverse scientific models, protective strategies and strong recommendations should be considered to reduce human exposure to protect present and future generations from their adverse health effects. Copyright

  5. Botulinum toxin A, brain and pain.

    Science.gov (United States)

    Matak, Ivica; Lacković, Zdravko

    2014-01-01

    Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Algal Toxins Alter Copepod Feeding Behavior

    Science.gov (United States)

    Hong, Jiarong; Talapatra, Siddharth; Katz, Joseph; Tester, Patricia A.; Waggett, Rebecca J.; Place, Allen R.

    2012-01-01

    Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major) to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod’s feeding appendages–a “sampling beating” that has short durations (<100 ms) and involves little fluid entrainment and a longer duration “grazing beating” that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod’s grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod’s feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods. PMID:22629336

  7. Algal toxins alter copepod feeding behavior.

    Directory of Open Access Journals (Sweden)

    Jiarong Hong

    Full Text Available Using digital holographic cinematography, we quantify and compare the feeding behavior of free-swimming copepods, Acartia tonsa, on nutritional prey (Storeatula major to that occurring during exposure to toxic and non-toxic strains of Karenia brevis and Karlodinium veneficum. These two harmful algal species produce polyketide toxins with different modes of action and potency. We distinguish between two different beating modes of the copepod's feeding appendages-a "sampling beating" that has short durations (<100 ms and involves little fluid entrainment and a longer duration "grazing beating" that persists up to 1200 ms and generates feeding currents. The durations of both beating modes have log-normal distributions. Without prey, A. tonsa only samples the environment at low frequency. Upon introduction of non-toxic food, it increases its sampling time moderately and the grazing period substantially. On mono algal diets for either of the toxic dinoflagellates, sampling time fraction is high but the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling and grazing diminish rapidly, presumably due to neurological effects of consuming brevetoxins while trying to feed on S. major. In contrast, on mixtures of cytotoxin producing K. veneficum, both behavioral modes persist, indicating that intake of karlotoxins does not immediately inhibit the copepod's grazing behavior. These findings add critical insight into how these algal toxins may influence the copepod's feeding behavior, and suggest how some harmful algal species may alter top-down control exerted by grazers like copepods.

  8. Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

    Science.gov (United States)

    Shiga toxin 1, exotoxin A, diphtheria toxin and ricin are all AB-type protein toxins that act within the host cytosol to kill the host cell through a pathway involving the inhibition of protein synthesis. It is thought that a single molecule of cytosolic toxin is sufficient to kill the host cell. In...

  9. Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

    International Nuclear Information System (INIS)

    Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

    1981-01-01

    Cholera toxin catalyzes transfer of radiolabel from [ 32 P]NAD + to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and [ 32 P]NAD + caused radiolabeling of purified microtubule and intermediate filament proteins

  10. Treatment of proctalgia fugax with botulinum A toxin.

    Science.gov (United States)

    Katsinelos, P; Kalomenopoulou, M; Christodoulou, K; Katsiba, D; Tsolkas, P; Pilpilidis, I; Papagiannis, A; Kapitsinis, I; Vasiliadis, I; Souparis, T

    2001-11-01

    Two recent studies described a temporal association between a high-amplitude and high-frequency myoelectrical activity of the anal sphincter and the occurrence of proctalgia, which suggest that paroxysmal hyperkinesis of the anus may cause proctalgia fugax. We describe a single case of proctalgia fugax responding to anal sphincter injection of Clostridium botulinum type A toxin. The presumed aetiology of proctalgia fugax is discussed and the possible mechanism of action of botulinum toxin (BTX) in this condition is outlined. Botulinum A toxin seems to be a promising treatment for patients with proctalgia fugax, and further trials appear to be worthwhile for this condition, which has been described as incurable.

  11. Cosmetic Effect of Botulinum Toxin In Focal Hyperhydrosis

    Directory of Open Access Journals (Sweden)

    Jain S

    2005-01-01

    Full Text Available Hyperhydrosis of axillae, palm and sole is not a very uncommon problem. It leads to great embarrassment and considerable emotional stress to the individuals. Botulinum toxins prevent the release of acetylcholine at nerve terminals, therefore, reduces sweat secretion. Six patients of axillary and 4 patients of palmer and planter hyperhydrosis were treated with botulinum toxin. All patients experienced relatively satisfactory reduction of hyperhydrosis for period ranging between 4-7 months. No adverse effects were observed. Botulinum toxin therefore can be considered as an effective treatment in focal hyperhydrosis.

  12. The effect of chronic feeding of diacetoxyscirpenol and T-2 toxin on performance, health, small intestinal physiology and antibody production in turkey poults.

    Science.gov (United States)

    Sklan, D; Shelly, M; Makovsky, B; Geyra, A; Klipper, E; Friedman, A

    2003-03-01

    1. The effects of feeding T-2 toxin or diacetoxyscirpenol (DAS) at levels up to 1 ppm for 32 d on performance, health, small intestinal physiology and immune response to enteral and parenteral immunisation were examined in young poults. 2. Slight improvement in growth was observed in some groups of poults fed T-2 or DAS mycotoxins for 32 d, with no change in feed efficiency. Feeding both T-2 and DAS resulted in oral lesions which had maximal severity after 7-15 d. 3. Mild intestinal changes were observed at 32 d but no pathological or histopathological lesions were found. Both mycotoxins altered small intestinal morphology, especially in the jejunum where villi were shorter and thinner. In addition, both DAS and T-2 mycotoxins enhanced the proportion of proliferating cells both in the crypts and along the villi. Migration rates were reduced in the jejunum of poults fed T-2 toxin but did not change in the duodenum or in poults fed DAS. 4. No significant effects of T-2 or DAS were observed on antibody production to antigens administered by enteral or parenteral routes. 5. This study indicates that tricothecene toxins at concentrations of up to 1 ppm for more than 30 d influenced small intestinal morphology but did not affect growth or antibody production.

  13. Coronavirus–associated enteritis in a quail farm

    Directory of Open Access Journals (Sweden)

    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.

  14. Monoclonal antibodies and toxins--a perspective on function and isotype.

    Science.gov (United States)

    Chow, Siu-Kei; Casadevall, Arturo

    2012-06-01

    Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

  15. Comparison of clinical marking and ultrasound-guided injection of Botulinum type A toxin into the masseter muscles for treating bruxism and its cosmetic effects.

    Science.gov (United States)

    Quezada-Gaon, Natacha; Wortsman, Ximena; Peñaloza, Osvaldo; Carrasco, Juan Eduardo

    2016-09-01

    Botulinum toxin type A has been used for treating the hypertrophy of the masseter muscles and its cosmetic effects. Ultrasound is increasingly used in dermatology, along with the guidance of mini-invasive procedures. To evaluate the role of ultrasound for guiding the application of Botulinum A toxin in patients with cosmetic alterations due to bruxism, correlate the clinical landmarks with the ultrasound findings, and study the effect on the symptoms, cosmetics, and quality of life. Twenty individuals with bruxism and cosmetic alterations underwent an ultrasound-guided injection of Botulinum toxin type A in each masseter muscle. Clinical and ultrasound marking of the procedure was compared. Clinical and sonographic evaluation was performed at the time of injection and 3 months later. Ten normal individuals underwent ultrasound of the masseter muscles as a control group. Up to 65% of individuals showed anatomical variants of the salivary glands. The method for clinically marking the skin showed a frequently erroneous location of the anterior point (up to 40% of cases) that was proven by ultrasound to be out of the muscle. In 20% of cases, ultrasound showed that the needle should be longer to enter the muscle. After injection, most of the patients demonstrated a decrease of the symptoms and cosmetic and quality of life improvements. Ultrasound can be a potent tool for guiding the injection of Botulinum toxin into the masseter muscles. It may contribute to a more personalized procedure, better cosmetic results, and help to avoid potential complications. © 2016 Wiley Periodicals, Inc.

  16. Enteral feeding pumps: efficacy, safety, and patient acceptability

    Directory of Open Access Journals (Sweden)

    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

  17. Loading and Light Degradation Characteristics of B t Toxin on Nano goethite: A Potential Material for Controlling the Environmental Risk of B t Toxin

    International Nuclear Information System (INIS)

    Zhou, X.; She, Ch.; She, Ch.; Liu, H.

    2015-01-01

    Transgenic B t-modified crops release toxins into soil through root exudate s and upon decomposition of residues. The fate of these toxins in soil has not been yet clearly elucidated. Nano goethite was found to have a different influence on the lifetime and identicalness activity of B t toxin. The aim of this study was to elucidate the adsorption characteristics of B t toxin on nano goethite and its activity changes before and after adsorption. The adsorption of toxin on nano goethite reached equilibrium within 5 h, and the adsorption isotherm of B t toxin on nano goethite conformed to the Langmuir equation (). In the range of ph from 6.0 to 8.0, larger adsorption occurred at lower ph value. The toxin adsorption decreased with the temperature between 10 and 50 degree. The results of Ftir, XRD, and SEM indicated that toxin did not influence the structure of nano goethite and the adsorption of toxin only on the surface of nano goethite. The LC_5_0 value for bound toxin was higher than that of free toxin, and the nano goethite greatly accelerated the degradation of toxin by ultraviolet irradiation. The above results suggested that nano goethite is a potential material for controlling the environmental risk of toxin released by Bt transgenic plants

  18. Syndromic diarrhea/Tricho-hepato-enteric syndrome

    Directory of Open Access Journals (Sweden)

    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

  19. In Vivo Tumor Targeting by the B-Subunit of Shiga Toxin

    Directory of Open Access Journals (Sweden)

    Thomas Viel

    2008-11-01

    Full Text Available Delivery of drugs to the appropriate target cells would improve efficacy and reduce potential side effects. The nontoxic B-subunit of the intestinal pathogen-produced Shiga toxin (STxB binds specifically to the glycosphingolipid Gb3, overex-pressed in membranes of certain tumor cells, and enters these cells through the retrograde pathway. Therefore, STxB binding to Gb3 receptors may be useful for cell-specific vectorization or imaging purposes. Here we labeled STxB with a fluorophore to evaluate its potential as an in vivo cell-specific targeting reagent in two different models of human colorectal carcinoma. Fluorescent STxB was administered systemically to xenografted nude mice, and its biodistribution was studied by optical imaging. The use of fluorescent STxB allowed the combination of the macroscopic observations with analyses at the cellular level using confocal microscopy. After administration, the fluorescent STxB was slowly eliminated by renal excretion. However, it accumulated in the tumor area. Furthermore, STxB was demonstrated to enter the Gb3-expressing tumoral cells, as well as the epithelial cells of the neovascularization and the monocytes and macrophages surrounding the xenografts.

  20. Bacterial toxin-antitoxin systems: more than selfish entities?

    Science.gov (United States)

    Van Melderen, Laurence; Saavedra De Bast, Manuel

    2009-03-01

    Bacterial toxin-antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.

  1. 42 CFR 73.3 - HHS select agents and toxins.

    Science.gov (United States)

    2010-10-01

    ... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are... Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

  2. 42 CFR 73.4 - Overlap select agents and toxins.

    Science.gov (United States)

    2010-10-01

    ... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

  3. 7 CFR 331.3 - PPQ select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

  4. Webinar Presentation: The Impact of Toxins on the Developing Brain

    Science.gov (United States)

    This presentation, The Impact of Toxins on the Developing Brain, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Historical Perspectives and Research Updates from Previously Funded Children's Centers held on Nov. 18, 2015.

  5. Botulinum toxin for treatment of the focal dystonia.

    Science.gov (United States)

    Nakamura, Yusaku

    2017-07-29

    Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.

  6. Three-Dimensional Structure Determination of Botulinum Toxin

    National Research Council Canada - National Science Library

    Stevens, Ray

    1997-01-01

    ...) Based on the structure of the neurotoxin, understand the toxins mechanism of action. We have accomplished the first goal of determining the three-dimensional structure of the 150 kD botulinum neurotoxin serotype...

  7. Three-Dimensional Structure Determination of Botulinum Toxin

    National Research Council Canada - National Science Library

    Stevens, Ray

    1998-01-01

    ...) Based on the structure of the neurotoxin, understand the toxins mechanism of action. We have accomplished the first goal of determining the three-dimensional structure of the 150 kD botulinum neurotoxin serotype...

  8. Two Contrasting Failure Modes of Enteric Coated Beads.

    Science.gov (United States)

    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.

  9. EFEKTIFITAS TOXIN BOTULLINUM UNTUK MANAJEMEN BLEFAROSPASME ESSENSIAL DAN SPASME HEMIFASIAL

    Directory of Open Access Journals (Sweden)

    Hendriati Hendriati

    2010-09-01

    Full Text Available AbstrakUntuk mengukur efektifikas toxin Botullinum pada kasus-kasus okuloplastik (blefarospasme essensial dan spasme hemifasial.Laporan kasus 16 pasien yang terdiri dari 14 kasus spasme hemifasial dan 2 kasus blefarospasme essensial. Digunakan 6 vial toxin Botullinum. Vial pertama digunakan untuk pasien spasme hemifasial dan 1 pasien blefasrospasme di minggu berikutnya. vial kedua dan ketiga masing-masing digunakan untuk 2 pasien spasme hemifasial. Vial keempat digunakan untuk pasien blefarospasme yang menggunakan vial pertama (setelah 6 bulan, dan 1 pasien spasme hemifasial yang menggunakan vial kedua ( setelah 4 bulan dan 1 pasien spasme hemifasial baru. Setelah 1 minggu, toxin Botullinum vial keempat digunakan untuk 6 pasien spasme hemifasial dan 1 pasien blefarospasme essensial yang menggunakan vial pertama 8 hari berikutnya (setelah 7 bulan.Terdapat 16 pasien pada studi ini ; 14 spasme hemifasial dan 2 blefarospasme essensial. Pada 5 pasien dilakukan injeksi ulangan dengan jangka waktu yang berbeda. Tidak ditemukan efek samping pada pasien-pasien ini.Toxin Botulinum efektif untuk manajemen spasme hemifasial dan blefarospasme essensial tetapi efeknya temporer. Pada studi ini, jangka waktu injeksi ulangan bervariasi sekitar 4 – 7 bulan pada 5 pasien.Kata Kunci : Toxin Botulinum toxin, spasme hemifasial, blefarospasmeAbstractTo asses Botulinum Toxin efficacy in oculoplastic cases (blepharospasm and hemifacial spasm.A case report on 16 patients consisted of 14 hemifacial spasms and 2 essential blepharospasm. Six vials of botulinum toxin were used. First vial was used for two patients of hemifacial spasm and one blepharospasm patient one week later. Second and third vials were used each for two patients of hemifacial spasms. Fourth vial was used for one blepharospasm patient from first vial user (after six month, one hemifacial spasm from second vial user (after four months and one new hemifacial spasm. After one week, Botulinum toxin from

  10. Identification of rice Os4BGlu13 as a β-glucosidase which hydrolyzes gibberellin A4 1-O-β-d-glucosyl ester, in addition to tuberonic acid glucoside and salicylic acid derivative glucosides.

    Science.gov (United States)

    Hua, Yanling; Ekkhara, Watsamon; Sansenya, Sompong; Srisomsap, Chantragan; Roytrakul, Sittiruk; Saburi, Wataru; Takeda, Ryosuke; Matsuura, Hideyuki; Mori, Haruhide; Ketudat Cairns, James R

    2015-10-01

    Gibberellin 1-O-β-d-glucose ester hydrolysis activity has been detected in rice seedling extracts, but no enzyme responsible for this activity has ever been purified and identified. Therefore, gibberellin A4 glucosyl ester (GA4-GE) β-d-glucosidase activity was purified from ten-day rice seedling stems and leaves. The family 1 glycoside hydrolase Os4BGlu13 was identified in the final purification fraction. The Os4BGlu13 cDNA was amplified from rice seedlings and expressed as an N-terminal thioredoxin-tagged fusion protein in Escherichia coli. The purified recombinant Os4BGlu13 protein (rOs4BGlu13) had an optimum pH of 4.5, for hydrolysis of p-nitrophenyl β-d-glucopyranoside (pNPGlc), which was the best substrate identified, with a kcat/Km of 637 mM(-1) s(-1). rOs4BGlu13 hydrolyzed helicin best among natural glycosides tested (kcat/Km of 74.4 mM(-1) s(-1)). Os4BGlu13 was previously designated tuberonic acid glucoside (TAG) β-glucosidase (TAGG), and here the kcat/Km of rOsBGlu13 for TAG was 6.68 mM(-1) s(-1), while that for GA4-GE was 3.63 mM(-1) s(-1) and for salicylic acid glucoside (SAG) is 0.88 mM(-1) s(-1). rOs4BGlu13 also hydrolyzed oligosaccharides, with preference for short β-(1 → 3)-linked over β-(1 → 4)-linked glucooligosaccharides. The enzymatic data suggests that Os4BGlu13 may contribute to TAG, SAG, oligosaccharide and GA4-GE hydrolysis in the rice plant, although helicin or a similar compound may be its primary target. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Dieta enteral prescrita versus dieta infundida Prescribed enteral diet versus infused diet

    Directory of Open Access Journals (Sweden)

    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.

  12. Alternaria Toxins: Potential Virulence Factors and Genes Related to Pathogenesis

    Directory of Open Access Journals (Sweden)

    Mukesh Meena

    2017-08-01

    Full Text Available Alternaria is an important fungus to study due to their different life style from saprophytes to endophytes and a very successful fungal pathogen that causes diseases to a number of economically important crops. Alternaria species have been well-characterized for the production of different host-specific toxins (HSTs and non-host specific toxins (nHSTs which depend upon their physiological and morphological stages. The pathogenicity of Alternaria species depends on host susceptibility or resistance as well as quantitative production of HSTs and nHSTs. These toxins are chemically low molecular weight secondary metabolites (SMs. The effects of toxins are mainly on different parts of cells like mitochondria, chloroplast, plasma membrane, Golgi complex, nucleus, etc. Alternaria species produce several nHSTs such as brefeldin A, tenuazonic acid, tentoxin, and zinniol. HSTs that act in very low concentrations affect only certain plant varieties or genotype and play a role in determining the host range of specificity of plant pathogens. The commonly known HSTs are AAL-, AK-, AM-, AF-, ACR-, and ACT-toxins which are named by their host specificity and these toxins are classified into different family groups. The HSTs are differentiated on the basis of bio-statistical and other molecular analyses. All these toxins have different mode of action, biochemical reactions and signaling mechanisms to cause diseases. Different species of Alternaria produced toxins which reveal its biochemical and genetic effects on itself as well as on its host cells tissues. The genes responsible for the production of HSTs are found on the conditionally dispensable chromosomes (CDCs which have been well characterized. Different bio-statistical methods like basic local alignment search tool (BLAST data analysis used for the annotation of gene prediction, pathogenicity-related genes may provide surprising knowledge in present and future.

  13. Genetic Markers for Western Corn Rootworm Resistance to Bt Toxin

    OpenAIRE

    Flagel, Lex E.; Swarup, Shilpa; Chen, Mao; Bauer, Christopher; Wanjugi, Humphrey; Carroll, Matthew; Hill, Patrick; Tuscan, Meghan; Bansal, Raman; Flannagan, Ronald; Clark, Thomas L.; Michel, Andrew P.; Head, Graham P.; Goldman, Barry S.

    2015-01-01

    Western corn rootworm (WCR) is a major maize (Zea mays L.) pest leading to annual economic losses of more than 1 billion dollars in the United States. Transgenic maize expressing insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt) are widely used for the management of WCR. However, cultivation of Bt-expressing maize places intense selection pressure on pest populations to evolve resistance. Instances of resistance to Bt toxins have been reported in WCR. Developing genet...

  14. Studies on marine toxins: chemical and biological aspects

    International Nuclear Information System (INIS)

    Stonik, Valentin A; Stonik, Inna V

    2010-01-01

    The structures and mechanisms of biological action of the best known representatives of the main groups of marine toxins are presented. It is shown that many compounds have complex chemical structures and possess extremely high toxicities. Characteristic features of isolation, structure determination and syntheses of these compounds using the achievement of modern organic chemistry are discussed. The methods of identification and quantitative analysis of marine toxins are briefly reviewed.

  15. Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

    OpenAIRE

    Mantzouki, Evanthia; Lürling, Miquel; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Seelen, Laura; Teurlincx, Sven; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma

    2018-01-01

    Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and li...

  16. Temperature effects explain continental scale distribution of cyanobacterial toxins

    OpenAIRE

    Mantzouki, Evanthia; Lürling, Miquel; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Seelen, Laura; Teurlincx, Sven; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma

    2018-01-01

    Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and li...

  17. Genetics and genomics of susceptibility and immune response to necrotic enteritis in chicken: a review.

    Science.gov (United States)

    Zahoor, Imran; Ghayas, Abdul; Basheer, Atia

    2018-02-01

    Global poultry production is facing many challenges and is currently under pressure due to the presence of several diseases like Necrotic Enteritis (NE). It is estimated that NE-caused global economic losses has increased from 2 billion to 6 billion US$ in 2015 because it is not easy to diagnose and control disease at the earlier stage of occurrence. Additionally, ban on the in-feed antibiotics and some other genetic and non-genetic predisposing factors affect the occurrence of the disease. Though the incidence of the disease can be reduced by minimizing the predisposing factors and through immunization of birds but there is no single remedy to control the disease. Therefore, we suggest that there is need to find out the genetic variants that could help to select the birds resistant to NE. The current review details the pertinent features about the genetic and genomics of susceptibility and immune response of birds to Necrotic Enteritis. We report here the list of candidate gene reported for their involvement with the susceptibility and/or resistance to the disease. However, most of these genes are involved in immune-related functions. For better understanding of the role of Clostridium perfringens and its toxins in the pathogenesis of disease there is need to unveil the association between any specific genetic variation and clinical status of NE. However, the presence of substantial genetic variations among different breeds/strains of chicken shows that it is possible to develop broiler strain with genetic resistant against NE. It would help in the cost-effective and sustainable production of safe broiler meat.

  18. Toxin-independent virulence of Bacillus anthracis in rabbits.

    Directory of Open Access Journals (Sweden)

    Haim Levy

    Full Text Available The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play a major role in pathogenicity. In the guinea pig (GP model we have previously shown that deletion of all three toxin components results in a relatively moderate attenuation in virulence, indicating that B. anthracis possesses an additional toxin-independent virulence mechanism. To characterize this toxin-independent mechanism in anthrax disease, we developed a new rabbit model by intravenous injection (IV of B. anthracis encapsulated vegetative cells, artificially creating bacteremia. Using this model we were able to demonstrate that also in rabbits, B. anthracis mutants lacking the toxins are capable of killing the host within 24 hours. This virulent trait depends on the activity of AtxA in the presence of pXO2, as, in the absence of the toxin genes, deletion of either component abolishes virulence. Furthermore, this IV virulence depends mainly on AtxA rather than the whole pXO1. A similar pattern was shown in the GP model using subcutaneous (SC administration of spores of the mutant strains, demonstrating the generality of the phenomenon. The virulent strains showed higher bacteremia levels and more efficient tissue dissemination; however our interpretation is that tissue dissemination per se is not the main determinant of virulence whose exact nature requires further elucidation.

  19. Doc toxin is a kinase that inactivates elongation factor Tu.

    Science.gov (United States)

    Cruz, Jonathan W; Rothenbacher, Francesca P; Maehigashi, Tatsuya; Lane, William S; Dunham, Christine M; Woychik, Nancy A

    2014-03-14

    The Doc toxin from bacteriophage P1 (of the phd-doc toxin-antitoxin system) has served as a model for the family of Doc toxins, many of which are harbored in the genomes of pathogens. We have shown previously that the mode of action of this toxin is distinct from the majority derived from toxin-antitoxin systems: it does not cleave RNA; in fact P1 Doc expression leads to mRNA stabilization. However, the molecular triggers that lead to translation arrest are not understood. The presence of a Fic domain, albeit slightly altered in length and at the catalytic site, provided a clue to the mechanism of P1 Doc action, as most proteins with this conserved domain inactivate GTPases through addition of an adenylyl group (also referred to as AMPylation). We demonstrated that P1 Doc added a single phosphate group to the essential translation elongation factor and GTPase, elongation factor (EF)-Tu. The phosphorylation site was at a highly conserved threonine, Thr-382, which was blocked when EF-Tu was treated with the antibiotic kirromycin. Therefore, we have established that Fic domain proteins can function as kinases. This distinct enzymatic activity exhibited by P1 Doc also solves the mystery of the degenerate Fic motif unique to the Doc family of toxins. Moreover, we have established that all characterized Fic domain proteins, even those that phosphorylate, target pivotal GTPases for inactivation through a post-translational modification at a single functionally critical acceptor site.

  20. Doc Toxin Is a Kinase That Inactivates Elongation Factor Tu*

    Science.gov (United States)

    Cruz, Jonathan W.; Rothenbacher, Francesca P.; Maehigashi, Tatsuya; Lane, William S.; Dunham, Christine M.; Woychik, Nancy A.

    2014-01-01

    The Doc toxin from bacteriophage P1 (of the phd-doc toxin-antitoxin system) has served as a model for the family of Doc toxins, many of which are harbored in the genomes of pathogens. We have shown previously that the mode of action of this toxin is distinct from the majority derived from toxin-antitoxin systems: it does not cleave RNA; in fact P1 Doc expression leads to mRNA stabilization. However, the molecular triggers that lead to translation arrest are not understood. The presence of a Fic domain, albeit slightly altered in length and at the catalytic site, provided a clue to the mechanism of P1 Doc action, as most proteins with this conserved domain inactivate GTPases through addition of an adenylyl group (also referred to as AMPylation). We demonstrated that P1 Doc added a single phosphate group to the essential translation elongation factor and GTPase, elongation factor (EF)-Tu. The phosphorylation site was at a highly conserved threonine, Thr-382, which was blocked when EF-Tu was treated with the antibiotic kirromycin. Therefore, we have established that Fic domain proteins can function as kinases. This distinct enzymatic activity exhibited by P1 Doc also solves the mystery of the degenerate Fic motif unique to the Doc family of toxins. Moreover, we have established that all characterized Fic domain proteins, even those that phosphorylate, target pivotal GTPases for inactivation through a post-translational modification at a single functionally critical acceptor site. PMID:24448800

  1. AB Toxins: A Paradigm Switch from Deadly to Desirable

    Directory of Open Access Journals (Sweden)

    Oludare Odumosu

    2010-06-01

    Full Text Available To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.

  2. Toxin studies using an integrated biophysical and structural biology approach.

    Energy Technology Data Exchange (ETDEWEB)

    Last, Julie A.; Schroeder, Anne E.; Slade, Andrea Lynn; Sasaki, Darryl Yoshio; Yip, Christopher M. (University of Toronto, Toronto, Ontario, Canada); Schoeniger, Joseph S. (Sandia National Laboratories, Livermore, CA)

    2005-03-01

    Clostridial neurotoxins, such as botulinum and tetanus, are generally thought to invade neural cells through a process of high affinity binding mediated by gangliosides, internalization via endosome formation, and subsequent membrane penetration of the catalytic domain activated by a pH drop in the endosome. This surface recognition and internalization process is still not well understood with regard to what specific membrane features the toxins target, the intermolecular interactions between bound toxins, and the molecular conformational changes that occur as a result of pH lowering. In an effort to elucidate the mechanism of tetanus toxin binding and permeation through the membrane a simple yet representative model was developed that consisted of the ganglioside G{sub tlb} incorporated in a bilayer of cholesterol and DPPC (dipalmitoylphosphatidyl choline). The bilayers were stable over time yet sensitive towards the binding and activity of whole toxin. A liposome leakage study at constant pH as well as with a pH gradient, to mimic the processes of the endosome, was used to elucidate the effect of pH on the toxin's membrane binding and permeation capability. Topographic imaging of the membrane surface, via in situ tapping mode AFM, provided nanoscale characterization of the toxin's binding location and pore formation activity.

  3. Toxin gene determination and evolution in scorpaenoid fish.

    Science.gov (United States)

    Chuang, Po-Shun; Shiao, Jen-Chieh

    2014-09-01

    In this study, we determine the toxin genes from both cDNA and genomic DNA of four scorpaenoid fish and reconstruct their evolutionary relationship. The deduced protein sequences of the two toxin subunits in Sebastapistes strongia, Scorpaenopsis oxycephala, and Sebastiscus marmoratus are about 700 amino acid, similar to the sizes of the stonefish (Synanceia horrida, and Synanceia verrucosa) and lionfish (Pterois antennata and Pterois volitans) toxins previously published. The intron positions are highly conserved among these species, which indicate the applicability of gene finding by using genomic DNA template. The phylogenetic analysis shows that the two toxin subunits were duplicated prior to the speciation of Scorpaenoidei. The precedence of the gene duplication over speciation indicates that the toxin genes may be common to the whole family of Scorpaeniform. Furthermore, one additional toxin gene has been determined in the genomic DNA of Dendrochirus zebra. The phylogenetic analysis suggests that an additional gene duplication occurred before the speciation of the lionfish (Pteroinae) and a pseudogene may be generally present in the lineage of lionfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Association of Bordetella dermonecrotic toxin with the extracellular matrix

    Directory of Open Access Journals (Sweden)

    Miyake Masami

    2010-09-01

    Full Text Available Abstract Background Bordetella dermonecrotic toxin (DNT causes the turbinate atrophy in swine atrophic rhinitis, caused by a Bordetella bronchiseptica infection of pigs, by inhibiting osteoblastic differentiation. The toxin is not actively secreted from the bacteria, and is presumed to be present in only small amounts in infected areas. How such small amounts can affect target tissues is unknown. Results Fluorescence microscopy revealed that DNT associated with a fibrillar structure developed on cultured cells. A cellular component cross-linked with DNT conjugated with a cross-linker was identified as fibronectin by mass spectrometry. Colocalization of the fibronectin network on the cells with DNT was also observed by fluorescence microscope. Several lines of evidence suggested that DNT interacts with fibronectin not directly, but through another cellular component that remains to be identified. The colocalization was observed in not only DNT-sensitive cells but also insensitive cells, indicating that the fibronectin network neither serves as a receptor for the toxin nor is involved in the intoxicating procedures. The fibronectin network-associated toxin was easily liberated when the concentration of toxin in the local environment decreased, and was still active. Conclusions Components in the extracellular matrix are known to regulate activities of various growth factors by binding and liberating them in response to alterations in the extracellular environment. Similarly, the fibronectin-based extracellular matrix may function as a temporary storage system for DNT, enabling small amounts of the toxin to efficiently affect target tissues or cells.

  5. Botulinum toxin A for the Treatment of Overactive Bladder.

    Science.gov (United States)

    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-02-29

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  6. Botulinum toxin treatment for facial palsy: A systematic review.

    Science.gov (United States)

    Cooper, Lilli; Lui, Michael; Nduka, Charles

    2017-06-01

    Facial palsy may be complicated by ipsilateral synkinesis or contralateral hyperkinesis. Botulinum toxin is increasingly used in the management of facial palsy; however, the optimum dose, treatment interval, adjunct therapy and performance as compared with alternative treatments have not been well established. This study aimed to systematically review the evidence for the use of botulinum toxin in facial palsy. The Cochrane central register of controlled trials (CENTRAL), MEDLINE(R) (1946 to September 2015) and Embase Classic + Embase (1947 to September 2015) were searched for randomised studies using botulinum toxin in facial palsy. Forty-seven studies were identified, and three included. Their physical and patient-reported outcomes are described, and observations and cautions are discussed. Facial asymmetry has a strong correlation to subjective domains such as impairment in social interaction and perception of self-image and appearance. Botulinum toxin injections represent a minimally invasive technique that is helpful in restoring facial symmetry at rest and during movement in chronic, and potentially acute, facial palsy. Botulinum toxin in combination with physical therapy may be particularly helpful. Currently, there is a paucity of data; areas for further research are suggested. A strong body of evidence may allow botulinum toxin treatment to be nationally standardised and recommended in the management of facial palsy. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Pufferfish mortality associated with novel polar marine toxins in Hawaii

    Science.gov (United States)

    Work, Thierry M.; Moeller, Perer D. R.; Beauchesne, Kevin R.; Dagenais, Julie; Breeden, Renee; Rameyer, Robert; Walsh, Willliam A.; Abecassis, Melanie; Kobayashi, Donald R.; Conway, Carla M.; Winton, James

    2017-01-01

    Fish die-offs are important signals in tropical marine ecosystems. In 2010, a mass mortality of pufferfish in Hawaii (USA) was dominated by Arothron hispidus showing aberrant neurological behaviors. Using pathology, toxinology, and field surveys, we implicated a series of novel, polar, marine toxins as a likely cause of this mass mortality. Our findings are striking in that (1) a marine toxin was associated with a kill of a fish species that is itself toxic; (2) we provide a plausible mechanism to explain clinical signs of affected fish; and (3) this epizootic likely depleted puffer populations. Whilst our data are compelling, we did not synthesize the toxin de novo, and we were unable to categorically prove that the polar toxins caused mortality or that they were metabolites of an undefined parent compound. However, our approach does provide a template for marine fish kill investigations associated with marine toxins and inherent limitations of existing methods. Our study also highlights the need for more rapid and cost-effective tools to identify new marine toxins, particularly small, highly polar molecules.

  8. Removal of cyanobacterial toxins by sediment passage

    Science.gov (United States)

    Gruetzmacher, G.; Boettcher, G.; Chorus, I.; Bartel, H.

    2003-04-01

    Cyanbacterial toxins ("Cyanotoxins") comprise a wide range of toxic substances produced by cyanobacteria ("blue-green algae"). Cyanobacteria occur in surface water word wide and can be found in high concentrations during so-called algal blooms when conditions are favourable (e.g. high nutrient levels, high temperatures). Some cyanobacteria produce hepato- or neurotoxins, of which the hepatotoxic microcystins are the most common in Germany. The WHO guideline value for drinking water was set at 1 μg/L. However, maximum concentrations in surface water can reach 25 mg/L, so that a secure method for toxin elimination has to be found when this water is used as source water for drinking water production. In order to assess if cyanotoxins can be removed by sediment passage the German Federal Environmental Agency (UBA) conducted laboratory- and field scale experiments as well as observations on bank filtration field sites. Laboratory experiments (batch- and column experiments for adsorption and degradation parameters) were conducted in order to vary a multitude of experimental conditions. These experiments were followed by field scale experiments on the UBA's experimental field in Berlin. This plant offers the unique possibility to conduct experiments on the behaviour of various agents - such as harmful substances - during infiltration and bank filtration under well-defined conditions on a field scale, and without releasing these substances to the environment. Finally the development of microcystin concentrations was observed between infiltrating surface water and a drinking water well along a transsecte of observation wells. The results obtained show that infiltration and bank filtration normally seem to be secure treatment methods for source water contaminated by microcystins. However, elimination was shown to be difficult under the following circumstances: - dying cyanobacterial population due to insufficient light and / or nutrients, low temperatures or application of

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

    NARCIS (Netherlands)

    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.

  10. Complications relating to enteral and parenteral nutrition in trauma ...

    African Journals Online (AJOL)

    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 ...

  11. Enteric pathogen modification by anaecic earthworm, Lampito Mauritii

    African Journals Online (AJOL)

    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 ...

  12. Lipophilic Toxins in WA - Clear and present danger: monitoring and management of lipophilic shellfish toxins in Washington State

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Lipophilic shellfish toxins comprise an extensive suite of compounds including those associated with the human syndromes known as diarrhetic shellfish poisoning...

  13. Detection of Cholera Toxin by Optical Methods: A Mechanism-Based Approach to the Generic Detection of Protein Toxins

    National Research Council Canada - National Science Library

    Young, Ronald

    1997-01-01

    ... after its ADP-ribosylation. The sensitive technique of fluorescence spectroscopy can be employed to monitor the action of cholera toxin without regards to the substituents on the acceptor molecule by use of epsilon NAD...

  14. Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients.

    Science.gov (United States)

    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.

  15. Can a toxin gene NAAT be used to predict toxin EIA and the severity of Clostridium difficile infection?

    Directory of Open Access Journals (Sweden)

    Mark I. Garvey

    2017-12-01

    Full Text Available Abstract Background Diagnosis of C. difficile infection (CDI is controversial because of the many laboratory methods available and their lack of ability to distinguish between carriage, mild or severe disease. Here we describe whether a low C. difficile toxin B nucleic acid amplification test (NAAT cycle threshold (CT can predict toxin EIA, CDI severity and mortality. Methods A three-stage algorithm was employed for CDI testing, comprising a screening test for glutamate dehydrogenase (GDH, followed by a NAAT, then a toxin enzyme immunoassay (EIA. All diarrhoeal samples positive for GDH and NAAT between 2012 and 2016 were analysed. The performance of the NAAT CT value as a classifier of toxin EIA outcome was analysed using a ROC curve; patient mortality was compared to CTs and toxin EIA via linear regression models. Results A CT value ≤26 was associated with ≥72% toxin EIA positivity; applying a logistic regression model we demonstrated an association between low CT values and toxin EIA positivity. A CT value of ≤26 was significantly associated (p = 0.0262 with increased one month mortality, severe cases of CDI or failure of first line treatment. The ROC curve probabilities demonstrated a CT cut off value of 26.6. Discussions Here we demonstrate that a CT ≤26 indicates more severe CDI and is associated with higher mortality. Samples with a low CT value are often toxin EIA positive, questioning the need for this additional EIA test. Conclusions A CT ≤26 could be used to assess the potential for severity of CDI and guide patient treatment.

  16. Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins.

    Science.gov (United States)

    Narayanaswami, Pushpa; Geisbush, Thomas; Tarulli, Andrew; Raynor, Elizabeth; Gautam, Shiva; Tarsy, Daniel; Gronseth, Gary

    2016-09-01

    Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Why do females use botulinum toxin injections?

    Directory of Open Access Journals (Sweden)

    Carter Singh

    2015-01-01

    Full Text Available Background: Botulinum toxin (BT use for enhancing the facial features has become a commonly accepted form of aesthetic intervention. This study conducted a self-report survey of female BT users in order to explore the motivating factors in its use (cost-benefit analysis. Settings and Design: This is a cross-sectional exploratory pilot study. Materials and Methods: Self-report questionnaires were administered to 41 consecutive clients attending an independent medical practice for BT injections for cosmetic purposes. All the participants were females and represented a range of age groups from the 20s to above 60s. Items in the nonstandardized questionnaire elicited questions relating to the reasons for and against BT use. Statistical Analysis Used: Descriptive analysis was used rather than inferential statistics, and involved ranking the responses according to the most likely reasons for using BT and disadvantages of its use. Results: In general, the primary motivating factor for BT use was to improve self-esteem, and the greatest disadvantage involved financial costs associated with the procedure. Conclusions: The main findings of this study suggest that females who use BT for aesthetic purposes are motivated by personal psychological gains (intrapersonal attributes rather than social gains (interpersonal factors. In other words, they do not believe that having BT will equate to being treated any better by other people but would rather provide them with confidence and satisfaction regarding their self-image.

  18. Bioluminescent bioreporter sensing of foodborne toxins

    Science.gov (United States)

    Fraley, Amanda C.; Ripp, Steven; Sayler, Gary S.

    2004-06-01

    Histamine is the primary etiological agent in the foodborne disease scombrotoxicosis, one of the most common food toxicities related to fish consumption. Procedures for detecting histamine in fish products are available, but are often too expensive or too complex for routine use. As an alternative, a bacterial bioluminescent bioreporter has been constructed to develop a biosensor system that autonomously responds to low levels of histamine. The bioreporter contains a promoterless Photorhabdus luminescens lux operon (luxCDABE) fused with the Vibrio anguillarum angR regulatory gene promoter of the anguibactin biosynthetic operon. The bioreporter emitted 1.46 times more bioluminescence than background, 30 minutes after the addition of 100mM histamine. However, specificity was not optimal, as this biosensor generated significant bioluminescence in the presence of L-proline and L-histidine. As a means towards improving histamine specificity, the promoter region of a histamine oxidase gene from Arthrobacter globiformis was cloned upstream of the promotorless lux operon from Photorhabdus luminescens. This recently constructed whole-cell, lux-based bioluminescent bioreporter is currently being tested for optimal performance in the presence of histamine in order to provide a rapid, simple, and inexpensive model sensor for the detection of foodborne toxins.

  19. SHELL DISEASES AND TOXINS REGULATED BY LAW

    Directory of Open Access Journals (Sweden)

    Natalija Topić Popović

    1999-06-01

    Full Text Available There is a long tradition of cultivating shells in Croatia, and the shell industry has a good perspective of further development. Since shells are delicate organisms that require special breeding conditions and climate, they are also subject to many diseases. Bonamiosis, haplospioridiosis, marteiliosis, microcytosis and perkinsosis are stated by the International Bureau for Epizootics as shell diseases that, in keeping with law, must be reported, and iridovirosis as a disease of a potential international importance. The same diseases are regulated by the Veterinary Law from 1997 as infectious diseases prevention of which is of an interest for the Republic of Croatia. Although, according to the law, it does not have to be prevented, in this article the disease Mytilicola is also described. According to the Health Department Statute from 1994, eatable part of shells are being tested for toxins of some marine dinoflagelates that can damage human health, and these are PSP (Paralytic Shellfish Poison, DSP (Diarrhoeic Shellfish Poison and NSP (Neuroparalytic Shellfish Poison.

  20. A toxin-binding alkaline phosphatase fragment synergizes Bt toxin Cry1Ac against susceptible and resistant Helicoverpa armigera.

    Directory of Open Access Journals (Sweden)

    Wenbo Chen

    Full Text Available Evolution of resistance by insects threatens the continued success of pest control using insecticidal crystal (Cry proteins from the bacterium Bacillus thuringiensis (Bt in sprays and transgenic plants. In this study, laboratory selection with Cry1Ac yielded five strains of cotton bollworm, Helicoverpa armigera, with resistance ratios at the median lethal concentration (LC50 of activated Cry1Ac ranging from 22 to 1700. Reduced activity and reduced transcription of an alkaline phosphatase protein that binds Cry1Ac was associated with resistance to Cry1Ac in the four most resistant strains. A Cry1Ac-binding fragment of alkaline phosphatase from H. armigera (HaALP1f was not toxic by itself, but it increased mortality caused by Cry1Ac in a susceptible strain and in all five resistant strains. Although synergism of Bt toxins against susceptible insects by toxin-binding fragments of cadherin and aminopeptidase N has been reported previously, the results here provide the first evidence of synergism of a Bt toxin by a toxin-binding fragment of alkaline phosphatase. The results here also provide the first evidence of synergism of a Bt toxin by any toxin-binding peptide against resistant insects.

  1. In vitro reconstitution of the Clostridium botulinum type D progenitor toxin.

    Science.gov (United States)

    Kouguchi, Hirokazu; Watanabe, Toshihiro; Sagane, Yoshimasa; Sunagawa, Hiroyuki; Ohyama, Tohru

    2002-01-25

    Clostridium botulinum type D strain 4947 produces two different sizes of progenitor toxins (M and L) as intact forms without proteolytic processing. The M toxin is composed of neurotoxin (NT) and nontoxic-nonhemagglutinin (NTNHA), whereas the L toxin is composed of the M toxin and hemagglutinin (HA) subcomponents (HA-70, HA-17, and HA-33). The HA-70 subcomponent and the HA-33/17 complex were isolated from the L toxin to near homogeneity by chromatography in the presence of denaturing agents. We were able to demonstrate, for the first time, in vitro reconstitution of the L toxin formed by mixing purified M toxin, HA-70, and HA-33/17. The properties of reconstituted and native L toxins are indistinguishable with respect to their gel filtration profiles, native-PAGE profiles, hemagglutination activity, binding activity to erythrocytes, and oral toxicity to mice. M toxin, which contained nicked NTNHA prepared by treatment with trypsin, could no longer be reconstituted to the L toxin with HA subcomponents, whereas the L toxin treated with proteases was not degraded into M toxin and HA subcomponents. We conclude that the M toxin forms first by assembly of NT with NTNHA and is subsequently converted to the L toxin by assembly with HA-70 and HA-33/17.

  2. Peracylated Glucosyl Kaempferols from Pasania dodonfifolia Leaf.

    Science.gov (United States)

    Chang, Chi-Chih; Lee, Shoei-Sheng

    2015-08-01

    Phytochemical investigation of the ethanolic extract of Pasania dodoniifolia leaf led to the isolation of four kaempferol 3-0-peracylated glucosides (1-4), together with four flavonoid glucosides (5-8), epicatechin (9), and (7S, 7'S, 8R, 8'R)-icariol A2 (10). Of these, kaempferol-3-O-(3",4"-di-O-acetyl-2"-O-(Z)-p- coumaroyl)-6"-O-(E)-p-coumaroyl)-beta-glucopyranoside (3) and 3-O-(3",4"-di-O-acetyl-2",6"-di-O-(Z)-p-coumaroyl)-beta-glucopyranoside (4) are new and their structures were elucidated by 2D NMR spectroscopic analyses and MS data.

  3. Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

    Science.gov (United States)

    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.

  4. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia.

    Science.gov (United States)

    Duarte, Gonçalo S; Castelão, Mafalda; Rodrigues, Filipe B; Marques, Raquel E; Ferreira, Joaquim; Sampaio, Cristina; Moore, Austen P; Costa, João

    2016-10-26

    This is an update of a Cochrane review first published in 2003. Cervical dystonia is the most common form of focal dystonia and is a disabling disorder characterised by painful involuntary head posturing. There are two available formulations of botulinum toxin, with botulinum toxin type A (BtA) usually considered the first line therapy for this condition. Botulinum toxin type B (BtB) is an alternative option, with no compelling theoretical reason why it might not be as- or even more effective - than BtA. To compare the efficacy, safety and tolerability of botulinum toxin type A (BtA) versus botulinum toxin type B (BtB) in people with cervical dystonia. To identify studies for this review we searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, reference lists of articles and conference proceedings. All elements of the search, with no language restrictions, were last run in October 2016. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) comparing BtA versus BtB in adults with cervical dystonia. Two independent authors assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed meta-analyses using the random-effects model, for the comparison BtA versus BtB to estimate pooled effects and corresponding 95% confidence intervals (95% CI). No prespecified subgroup analyses were carried out. The primary efficacy outcome was improvement on any validated symptomatic rating scale, and the primary safety outcome was the proportion of participants with adverse events. We included three RCTs, all new to this update, of very low to low methodological quality, with a total of 270 participants.Two studies exclusively enrolled participants with a known positive response to BtA treatment. This raises concerns of population enrichment

  5. Toxin formation by Clostridium botulinum type B in radurized fish

    International Nuclear Information System (INIS)

    Suhadi, F.; Thayib, S.S.

    1981-01-01

    The relation between maximum storage life and earliest toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in irradiated and unirradiated raw fish was determinated. The fish species used were Rastrelliger sp., Euthynnus sp. and Scomberomorus sp. Uninoculated fish samples held under the same treatment conditions were evaluated for the estimation of storage life by untrained panelist. The results showed that a storage temperature at or lower than 5.6 0 C is recommended in order to avoid botulism hazard caused by nonproteolytic type B. When the samples were inoculated with spores of proteolytic strains, no toxic samples were found during the storage life in all treatments with storage temperatures at or lower than 10.2 0 C. Toxin formation by proteolytic strains of C. botulinum type B in boiled (''Pindang'') chub mackerel (Rastrelliger sp.) under storage at ambient temperatures (27-31 0 C) was also determinated. The results showed that in the samples which were inoculated before the process of ''Pindang'', the earliest toxin formations were detected after the samples were spoiled regardless of the irradiation dose, strain and inoculum level; while in control unsalted samples, toxin was detected before or after the samples were spoiled, depending on the strain and inoculum level. Salt content in ordinary ''Pindang'' fish plays a major role both in extension of the storage life and the delay in toxin formation. When the samples were inoculated after the process of ''Pindang'', toxin was detected before or after the samples were spoiled, depending on the strain, salt content, irradiation dose and inoculum level. Irradiation does not prevent the toxin formation in ''Pindang'' fish if the samples are heavily contaminated with proteolytic strains of C. botulinum type B after cooking. (author)

  6. Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay.

    Directory of Open Access Journals (Sweden)

    Richard J Lewis

    Full Text Available Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins.We established a simplified procedure for extracting polyether toxins from Gambierdiscus and Fukuyoa spp. based on the ciguatoxin rapid extraction method (CREM. Fractionated extracts from identified Pacific and Caribbean isolates were analysed using a functional bioassay that recorded intracellular calcium changes (Ca2+ in response to sample addition in SH-SY5Y cells. Maitotoxin directly elevated Ca2+i, while low levels of ciguatoxin-like toxins were detected using veratridine to enhance responses.We identified significant maitotoxin production in 11 of 12 isolates analysed, with 6 of 12 producing at least two forms of maitotoxin. In contrast, only 2 Caribbean isolates produced detectable levels of ciguatoxin-like activity despite a detection limit of >30 pM. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same Gambierdiscus spp. were also identified.The ability to rapidly identify polyether toxins produced by Gambierdiscus spp. in culture has the potential to distinguish ciguatoxin-producing species prior to large-scale culture and in naturally occurring blooms of Gambierdiscus and Fukuyoa spp. Our results have implications for the evaluation of ciguatera risk associated with Gambierdiscus and related species.

  7. The inhibition of cholera toxin-induced 5-HT release by the 5-HT3 receptor antagonist, granisetron, in the rat

    Science.gov (United States)

    Turvill, J L; Connor, P; Farthing, M J G

    2000-01-01

    The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT2 dependent) and neuronally (5-HT3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT3 receptors, the activation of which is known to enhance 5-HT release. Until now, 5-HT3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 μg kg−1, lidoocaine 6 mg kg−1 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT3 receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. PMID:10882387

  8. Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay.

    Science.gov (United States)

    Lewis, Richard J; Inserra, Marco; Vetter, Irina; Holland, William C; Hardison, D Ransom; Tester, Patricia A; Litaker, R Wayne

    2016-01-01

    Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins. We established a simplified procedure for extracting polyether toxins from Gambierdiscus and Fukuyoa spp. based on the ciguatoxin rapid extraction method (CREM). Fractionated extracts from identified Pacific and Caribbean isolates were analysed using a functional bioassay that recorded intracellular calcium changes (Ca2+) in response to sample addition in SH-SY5Y cells. Maitotoxin directly elevated Ca2+i, while low levels of ciguatoxin-like toxins were detected using veratridine to enhance responses. We identified significant maitotoxin production in 11 of 12 isolates analysed, with 6 of 12 producing at least two forms of maitotoxin. In contrast, only 2 Caribbean isolates produced detectable levels of ciguatoxin-like activity despite a detection limit of >30 pM. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same Gambierdiscus spp. were also identified. The ability to rapidly identify polyether toxins produced by Gambierdiscus spp. in culture has the potential to distinguish ciguatoxin-producing species prior to large-scale culture and in naturally occurring blooms of Gambierdiscus and Fukuyoa spp. Our results have implications for the evaluation of ciguatera risk associated with Gambierdiscus and related species.

  9. Cellular changes in the enteric nervous system during ageing.

    Science.gov (United States)

    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

  10. Pediatric Enteric Feeding Techniques: Insertion, Maintenance, and Management of Problems

    International Nuclear Information System (INIS)

    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.

  11. Toxins not neutralized by brown snake antivenom

    International Nuclear Information System (INIS)

    Judge, Roopwant K.; Henry, Peter J.; Mirtschin, Peter; Jelinek, George; Wilce, Jacqueline A.

    2006-01-01

    The Australian snakes of the genus Pseudonaja (dugite, gwardar and common brown) account for the majority of snake bite related deaths in Australia. Without antivenom treatment, the risk of mortality is significant. There is an accumulating body of evidence to suggest that the efficacy of the antivenom is limited. The current study investigates the protein constituents recognized by the antivenom using 2-DE, immuno-blot techniques and rat tracheal organ bath assays. The 2-DE profiles for all three snake venoms were similar, with major species visualized at 78-132 kDa, 32-45 kDa and 6-15 kDa. Proteins characterized by LC-MS/MS revealed a coagulant toxin (∼42 kDa) and coagulant peptide (∼6 kDa), as well as two PLA 2 (∼14 kDa). Peptides isolated from ∼78 kDa and 15-32 kDa protein components showed no similarity to known protein sequences. Protein recognition by the antivenom occurred predominantly for the higher molecular weight components with little recognition of 6-32 kDa MW species. The ability of antivenom to neutralize venom activity was also investigated using rat tracheal organ bath assays. The venoms of Pseudonaja affinis affinis and Pseudonaja nuchalis incited a sustained, significant contraction of the trachea. These contractions were attributed to PLA 2 enzymatic activity as pre-treatment with the PLA 2 inhibitor 4-BPB attenuated the venom-induced contractions. The venom of Pseudonaja textilis incited tracheal contractility through a non-PLA 2 enzymatic activity. Neither activity was attenuated by the antivenom treatment. These results represent the first proteomic investigation of the venoms from the snakes of the genus Pseudonaja, revealing a possible limitation of the brown snake antivenom in binding to the low MW protein components

  12. Endoribonuclease type II toxin-antitoxin systems: functional or selfish?

    Science.gov (United States)

    Ramisetty, Bhaskar Chandra Mohan; Santhosh, Ramachandran Sarojini

    2017-07-01

    Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids. However, the programmed cell death and persistence hypotheses have been challenged because of conceptual, methodological and/or strain issues. In an alternative view, chromosomal TAs seem to be retained by virtue of addiction at two levels: via a poison-antidote combination (TA proteins) and via transcriptional reprogramming of the downstream core gene (due to integration). Any perturbation in the chromosomal TA operons could cause fitness loss due to polar effects on the downstream genes and hence be detrimental under natural conditions. The endoribonucleases encoding chromosomal TAs are most likely selfish DNA as they are retained by bacterial genomes, even though TAs do not confer a direct advantage via the TA proteins. TAs are likely used by various replicons as 'genetic arms' that allow the maintenance of themselves and associated genetic elements. TAs seem to be the 'selfish arms' that make the best use of the 'arms race' between bacterial genomes and plasmids.

  13. The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

    Science.gov (United States)

    Martin-Verstraete, Isabelle; Peltier, Johann; Dupuy, Bruno

    2016-01-01

    The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection. PMID:27187475

  14. Biooxidation of Ciguatoxins Leads to Species-Specific Toxin Profiles.

    Science.gov (United States)

    Ikehara, Tsuyoshi; Kuniyoshi, Kyoko; Oshiro, Naomasa; Yasumoto, Takeshi

    2017-06-29

    Ciguatoxins (CTXs) contaminate fish worldwide and cause the foodborne illness ciguatera. In the Pacific, these toxins are produced by the dinoflagellate Gambierdiscus toxicus , which accumulates in fish through the food chain and undergoes oxidative modification, giving rise to numerous analogs. In this study, we examined the oxidation of CTXs in vitro with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using reference toxins, and found that CTX4A, CTX4B, and CTX3C, which are produced by the alga, are oxidized to the analogs found in fish, namely CTX1B, 52- epi -54-deoxyCTX1B, 54-deoxyCTX1B, 2-hydroxyCTX3C, and 2,3-dihydroxyCTX3C. This oxidation was catalyzed by human CYP3A4, fish liver S9 fractions, and microsomal fractions prepared from representative ciguateric fishes ( Lutjanus bohar , L. monostigumus , and Oplegnathus punctatus ). In addition, fish liver S9 fractions prepared from non-ciguateric fishes ( L. gibbus and L. fulviflamma ) in Okinawa also converted CTX4A and CTX4B to CTX1B, 54-deoxyCTX1B, and 52- epi -54-deoxyCTX1B in vitro. This is the first study to demonstrate the enzymatic oxidation of these toxins, and provides insight into the mechanism underlying the development of species-specific toxin profiles and the fate of these toxins in humans and fish.

  15. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    Science.gov (United States)

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-09-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  16. Evolution of Bacillus thuringiensis Cry toxins insecticidal activity.

    Science.gov (United States)

    Bravo, Alejandra; Gómez, Isabel; Porta, Helena; García-Gómez, Blanca Ines; Rodriguez-Almazan, Claudia; Pardo, Liliana; Soberón, Mario

    2013-01-01

    Insecticidal Cry proteins produced by Bacillus thuringiensis are use worldwide in transgenic crops for efficient pest control. Among the family of Cry toxins, the three domain Cry family is the better characterized regarding their natural evolution leading to a large number of Cry proteins with similar structure, mode of action but different insect specificity. Also, this group is the better characterized regarding the study of their mode of action and the molecular basis of insect specificity. In this review we discuss how Cry toxins have evolved insect specificity in nature and analyse several cases of improvement of Cry toxin action by genetic engineering, some of these examples are currently used in transgenic crops. We believe that the success in the improvement of insecticidal activity by genetic evolution of Cry toxins will depend on the knowledge of the rate-limiting steps of Cry toxicity in different insect pests, the mapping of the specificity binding regions in the Cry toxins, as well as the improvement of mutagenesis strategies and selection procedures. © 2012 The Authors. Microbial Biotechnology © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  17. Removal of Cholera Toxin from Aqueous Solution by Probiotic Bacteria

    Directory of Open Access Journals (Sweden)

    Jussi A. O. Meriluoto

    2012-06-01

    Full Text Available Cholera remains a serious health problem, especially in developing countries where basic hygiene standards are not met. The symptoms of cholera are caused by cholera toxin, an enterotoxin, which is produced by the bacterium Vibrio cholerae. We have recently shown that human probiotic bacteria are capable of removing cyanobacterial toxins from aqueous solutions. In the present study we investigate the ability of the human probiotic bacteria, Lactobacillus rhamnosus strain GG (ATCC 53103 and Bifidobacterium longum 46 (DSM 14583, to remove cholera toxin from solution in vitro. Lactobacillus rhamnosus strain GG and Bifidobacterium longum 46 were able to remove 68% and 59% of cholera toxin from aqueous solutions during 18 h of incubation at 37 °C, respectively. The effect was dependent on bacterial concentration and L. rhamnosus GG was more effective at lower bacterial concentrations. No significant effect on cholera toxin concentration was observed when nonviable bacteria or bacterial supernatant was used.

  18. Escherichia coli Shiga Toxin Mechanisms of Action in Renal Disease

    Directory of Open Access Journals (Sweden)

    Tom G. Obrig

    2010-12-01

    Full Text Available Shiga toxin-producing Escherichia coli is a contaminant of food and water that in humans causes a diarrheal prodrome followed by more severe disease of the kidneys and an array of symptoms of the central nervous system. The systemic disease is a complex referred to as diarrhea-associated hemolytic uremic syndrome (D+HUS. D+HUS is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. This review focuses on the renal aspects of D+HUS. Current knowledge of this renal disease is derived from a combination of human samples, animal models of D+HUS, and interaction of Shiga toxin with isolated renal cell types. Shiga toxin is a multi-subunit protein complex that binds to a glycosphingolipid receptor, Gb3, on select eukaryotic cell types. Location of Gb3 in the kidney is predictive of the sites of action of Shiga toxin. However, the toxin is cytotoxic to some, but not all cell types that express Gb3. It also can cause apoptosis or generate an inflammatory response in some cells. Together, this myriad of results is responsible for D+HUS disease.

  19. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  20. Treatment of Palatal Myoclonus with Botulinum Toxin Injection

    Directory of Open Access Journals (Sweden)

    Mursalin M. Anis

    2013-01-01

    Full Text Available Palatal myoclonus is a rare cause of pulsatile tinnitus in patients presenting to the otolaryngology office. Rhythmic involuntary contractions of the palatal muscles produce the pulsatile tinnitus in these patients. Treatment of this benign but distressing condition with anxiolytics, anticonvulsants, and surgery has been largely unsuccessful. A few investigators have obtained promising results with botulinum toxin injection into the palatal muscles. We present a patient with palatal myoclonus who failed conservative treatment with anxiolytics. Unilateral injection of botulinum toxin into her tensor veli palatini muscle under electromyographic guidance resolved pulsatile tinnitus in her ipsilateral ear and unmasked pulsatile tinnitus in the contralateral ear. A novel method of following transient postinjection symptoms using a diary is presented in this study. Botulinum toxin dose must be titrated to achieve optimal results in each individual patient, analogous to titrations done for spasmodic dysphonia. Knowledge of the temporal onset of postinjection side effects and symptomatic relief may aid physicians in dose titration and surveillance. We present suggestions on titrating the botulinum toxin dose to optimal levels. A review of the literature on the use of botulinum toxin for palatal myoclonus and some common complications are discussed.

  1. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  2. Communication Skill Attributes Needed for Vocational Education enter The Workplace

    Science.gov (United States)

    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

  3. High enteric bacterial contamination of drinking water in Jigjiga city ...

    African Journals Online (AJOL)

    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.

  4. Problems experienced by women re-entering the education profession

    African Journals Online (AJOL)

    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 ...

  5. Parenteral and Early Enteral Feeding in Patients with Colonic Tumor

    Directory of Open Access Journals (Sweden)

    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.

  6. Nurses' Competency and Challenges in Enteral feeding in the ...

    African Journals Online (AJOL)

    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.

  7. Environmental enteric dysfunction is associated with altered bile acid metabolism

    Science.gov (United States)

    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...

  8. Epigenetic regulation of enteric neurotransmission by gut bacteria.

    Directory of Open Access Journals (Sweden)

    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.

  9. Emerging antibiotic resistant enteric bacterial flora among food ...

    African Journals Online (AJOL)

    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 ...

  10. Quantification of gut lesions in a subclinical necrotic enteritis model

    DEFF Research Database (Denmark)

    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....

  11. Antimicrobial effect of Malaysian vegetables against enteric bacteria

    Directory of Open Access Journals (Sweden)

    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.

  12. [Biological evaluation of a protein mixture intended for enteral nutrition].

    Science.gov (United States)

    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.

  13. Treatment of displaced mandibular condylar fracture with botulinum toxin A.

    Science.gov (United States)

    Akbay, Ercan; Cevik, Cengiz; Damlar, Ibrahim; Altan, Ahmet

    2014-04-01

    The aim of this case report is to discuss the effect on condylar reduction of botulinum toxin A treatment used in a child with displaced fracture at condylar neck of mandible. A 3-years old boy was admitted to our clinic for incomplete fracture of mandibular symphysis and displaced condylar fracture at the left side. An asymmetrical occlusal splint with intermaxillary fixation was used instead of open reduction and internal fixation because of incomplete fracture of symphysis and possible complications of condyle surgery. However, it was observed that condylar angulation persisted despite this procedure. Thus, botulinum toxin A was administered to masseter, temporalis and pterygoideus medialis muscles. At the end of first month, it was seen that mandibular condyle was almost completely recovered and that fusion was achieved. In conclusion, Botulinum A toxin injection aiming the suppression of masticatory muscle strength facilitates the reduction in the conservative management of displaced condyle in pediatric patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Selective effects of an octopus toxin on action potentials

    Science.gov (United States)

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  15. Botulinum Toxin for the Treatment of Tremor and Tics.

    Science.gov (United States)

    Lotia, Mitesh; Jankovic, Joseph

    2016-02-01

    The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. CD28: Direct and Critical Receptor for Superantigen Toxins

    Directory of Open Access Journals (Sweden)

    Ziv Rotfogel

    2013-09-01

    Full Text Available Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on T-cells functioning as principal costimulatory receptor. Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell-mediated immune response by orders of magnitude, inducing a lethal cytokine storm. We show that to elicit an inflammatory cytokine storm and lethality, superantigens must bind directly to CD28. Blocking access of the superantigen to its CD28 receptor with peptides mimicking the contact domains in either toxin or CD28 suffices to protect mice effectively from lethal shock. Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms.

  17. Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

    Directory of Open Access Journals (Sweden)

    Kuan-Hsiang Lin

    2013-05-01

    Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

  18. 77 FR 61083 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review

    Science.gov (United States)

    2012-10-05

    ... inhibitory effects on bacterial cells of over-expressed toxin; and There are limitations to purification and... require large quantities of toxin for delivery by food, water, or air. We have considered all of the...

  19. Application and Development of Biological AFM for the Study of Bacterial Toxins

    National Research Council Canada - National Science Library

    Yang, Jie

    1999-01-01

    ... with other conventional methods. These studies have also established a solid foundation for our structural elucidation of molecular level conformation of membranous bacterial toxins, such as cholera toxin and alpha-hemolysin...

  20. Announcing the 2016 Toxins Travel Awards for Post-Doctoral Fellows and Ph.D. Students

    OpenAIRE

    Tesh, Vernon L.

    2016-01-01

    With the goal of promoting the development of early career investigators in the field of toxinology, Toxins welcomed applications for the 2016 Toxins Travel Awards for post-doctoral fellows and Ph.D. students. [...

  1. Announcing the 2016 Toxins Travel Awards for Post-Doctoral Fellows and Ph.D. Students

    Directory of Open Access Journals (Sweden)

    Vernon L. Tesh

    2016-02-01

    Full Text Available With the goal of promoting the development of early career investigators in the field of toxinology, Toxins welcomed applications for the 2016 Toxins Travel Awards for post-doctoral fellows and Ph.D. students. [...

  2. Toxin production in food as influenced by pH, thermal treatment and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... toxigenic properties and thirteen of the sixteen were positive for toxin production ... treatment and chemical preservatives on the growth rate and toxin ..... Clostridium botulinum in cooked pureed vegetables at Refrigerated.

  3. 42 CFR 73.10 - Restricting access to select agents and toxins; security risk assessments.

    Science.gov (United States)

    2010-10-01

    ... have access at any point in time if the individual has possession of a select agent or toxin (e.g., ability to carry, use, or manipulate) or the ability to gain possession of a select agent or toxin. (c...

  4. Brown Spider (Loxosceles genus Venom Toxins: Tools for Biological Purposes

    Directory of Open Access Journals (Sweden)

    Andrea Senff-Ribeiro

    2011-03-01

    Full Text Available Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus venom is enriched in low molecular mass proteins (5–40 kDa. Although their venom is produced in minute volumes (a few microliters, and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins.

  5. Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis

    OpenAIRE

    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...

  6. Radiation resistance of paralytic shellfish poison (PSP) toxins

    Energy Technology Data Exchange (ETDEWEB)

    San Juan, Edith M

    2000-04-01

    Radiation resistance of paralytic shellfish poison (PSP) toxins, obtained from Pyrodinium bahamense var. compressum in shellstocks of green mussels, was determined by subjecting the semi-purified toxin extract as well as the shellstocks of green mussels to high doses of ionizing radiation of 5, 10, 15 and 20 kGy. The concentration of the PSP toxins was determined by the Standard Mouse Bioassay (SMB) method. The radiation assistance of the toxins was determined by plotting the PSP toxin concentration versus applied dose in a semilog paper. The D{sub 10} value or decimal reduction dose was obtained from the straight line which is the dose required to reduce the toxicity level by 90%. The effects of irradiation on the quality of green mussels in terms of its physico-chemical, microbiological and sensory attributes were also conducted. The effect of irradiation on the fatty acid components of green mussels was determined by gas chromatography. Radiation resistance of the PSP toxins was determined to be lower in samples with initially high toxicity level as compared with samples with initially low toxicity level. The D{sub 10} values of samples with initially high PSP level were 28.5 kGy in shellstocks of green musssels and 17.5 kGy in the semi-purified toxin extract. When the PSP level was low initially, the D{sub 10} values were as high as 57.5 and 43.5 kGy in shellstocks of green mussels for the two trials, and 43.0 kGy in semi-purified toxin extract. The microbial load of the irradiated mussels was remarkably reduced. No differnce in color and odor characteristics were observed in the mussel samples subjected to varying doses of ionizing radiation. There was darkening in the color of mussel meat and its juice. The concentration of the fatty acid components in the fresh green mussels were considerably higher as compared with those present in the irradiated mussels, though some volatile fatty acids were detected as a result of irradiation. (Author)

  7. Radiation resistance of paralytic shellfish poison (PSP) toxins

    International Nuclear Information System (INIS)

    San Juan, Edith M.

    2000-04-01

    Radiation resistance of paralytic shellfish poison (PSP) toxins, obtained from Pyrodinium bahamense var. compressum in shellstocks of green mussels, was determined by subjecting the semi-purified toxin extract as well as the shellstocks of green mussels to high doses of ionizing radiation of 5, 10, 15 and 20 kGy. The concentration of the PSP toxins was determined by the Standard Mouse Bioassay (SMB) method. The radiation assistance of the toxins was determined by plotting the PSP toxin concentration versus applied dose in a semilog paper. The D 10 value or decimal reduction dose was obtained from the straight line which is the dose required to reduce the toxicity level by 90%. The effects of irradiation on the quality of green mussels in terms of its physico-chemical, microbiological and sensory attributes were also conducted. The effect of irradiation on the fatty acid components of green mussels was determined by gas chromatography. Radiation resistance of the PSP toxins was determined to be lower in samples with initially high toxicity level as compared with samples with initially low toxicity level. The D 10 values of samples with initially high PSP level were 28.5 kGy in shellstocks of green musssels and 17.5 kGy in the semi-purified toxin extract. When the PSP level was low initially, the D 10 values were as high as 57.5 and 43.5 kGy in shellstocks of green mussels for the two trials, and 43.0 kGy in semi-purified toxin extract. The microbial load of the irradiated mussels was remarkably reduced. No differnce in color and odor characteristics were observed in the mussel samples subjected to varying doses of ionizing radiation. There was darkening in the color of mussel meat and its juice. The concentration of the fatty acid components in the fresh green mussels were considerably higher as compared with those present in the irradiated mussels, though some volatile fatty acids were detected as a result of irradiation. (Author)

  8. Alpha-Toxin Promotes Mucosal Biofilm Formation by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Michele J Anderson

    2012-05-01

    Full Text Available Staphylococcus aureus causes numerous diseases in humans ranging from the mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS. S. aureus may also be asymptomatically carried in the anterior nares, vagina or on the skin, which serve as reservoirs for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and a major cause of TSS. Our prior studies indicated that α-toxin was a major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. It also facilitated the penetration of TSS Toxin-1 (TSST-1 across vaginal mucosa. However, the majority of menstrual TSS isolates produce low α-toxin due to a nonsense point mutation at codon 113, designated hly, suggesting mucosal adaptation. The aim of this study was to characterize the differences between TSS USA200 strains [high (hla+ and low (hly+ α-toxin producers] in their abilities to infect and disrupt vaginal mucosal tissue. A mucosal model was developed using ex vivo porcine vaginal mucosa, LIVE/DEAD® staining and confocal microscropy to characterize biofilm formation and tissue viability of TSS USA 200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hly, MNPE (hla+ and MNPE isogenic hla knockout (hlaKO. All TSS strains grew to similar bacterial densities (1-5 x 108 CFU on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587, MN8 (hly+, or MNPE hlaKO, formed biofilms and were less cytotoxic. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. Our studies suggest α-toxin affects S. aureus phenotypic growth on vaginal mucosa, by promoting tissue disruption and biofilm formation; and α–toxin mutants (hly are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic

  9. Botulinum toxin (BoNT) and back pain.

    Science.gov (United States)

    Porta, Mauro; Maggioni, G

    2004-02-01

    Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.

  10. BOTULINUM TOXIN FOR THE TREATMENT OF CHRONIC HEADACHE

    Directory of Open Access Journals (Sweden)

    L. B. Zavaliy

    2015-01-01

    Full Text Available ABSTRACT. The article deals with the use of botulinum toxin in the treatment of chronic headache. We present four clinical cases of patients who sought treatment in the “Pain Clinic” of N.V. Sklifosovsky Research Institute for Emergency Medicine with a chronic severe cephalgic syndrome of different genesis (migraine, tension headache, dystonia, which had not responded to outpatient treatment for a long time. The paper shows the change of pain in patients with various forms of headache after treatment with botulinum toxin type A, indicating the effectiveness of the method in these patients. 

  11. Bacterial community affects toxin production by Gymnodinium catenatum.

    Directory of Open Access Journals (Sweden)

    Maria E Albinsson

    Full Text Available The paralytic shellfish toxin (PST-producing dinoflagellate Gymnodinium catenatum grows in association with a complex marine bacterial community that is both essential for growth and can alter culture growth dynamics. Using a bacterial community replacement approach, we examined the intracellular PST content, production rate, and profile of G. catenatum cultures grown with bacterial communities of differing complexity and composition. Clonal offspring were established from surface-sterilized resting cysts (produced by sexual crosses of strain GCDE06 and strain GCLV01 and grown with: 1 complex bacterial communities derived from each of the two parent cultures; 2 simplified bacterial communities composed of the G. catenatum-associated bacteria Marinobacter sp. strain DG879 or Alcanivorax sp. strain DG881; 3 a complex bacterial community associated with an untreated, unsterilized sexual cross of the parents. Toxin content (STX-equivalent per cell of clonal offspring (134-197 fmol STX cell(-1 was similar to the parent cultures (169-206 fmol STX cell(-1, however cultures grown with single bacterial types contained less toxin (134-146 fmol STX cell(-1 than offspring or parent cultures grown with more complex mixed bacterial communities (152-176 fmol STX cell(-1. Specific toxin production rate (fmol STX day(-1 was strongly correlated with culture growth rate. Net toxin production rate (fmol STX cell(-1 day(-1 did not differ among treatments, however, mean net toxin production rate of offspring was 8-fold lower than the parent cultures, suggesting that completion of the sexual lifecycle in laboratory cultures leads to reduced toxin production. The PST profiles of offspring cultures were most similar to parent GCDE06 with the exception of cultures grown with Marinobacter sp. DG879 which produced higher proportions of dcGTX2+3 and GC1+2, and lower proportions of C1+2 and C3+4. Our data demonstrate that the bacterial community can alter intracellular STX

  12. Bacterial community affects toxin production by Gymnodinium catenatum.

    Science.gov (United States)

    Albinsson, Maria E; Negri, Andrew P; Blackburn, Susan I; Bolch, Christopher J S

    2014-01-01

    The paralytic shellfish toxin (PST)-producing dinoflagellate Gymnodinium catenatum grows in association with a complex marine bacterial community that is both essential for growth and can alter culture growth dynamics. Using a bacterial community replacement approach, we examined the intracellular PST content, production rate, and profile of G. catenatum cultures grown with bacterial communities of differing complexity and composition. Clonal offspring were established from surface-sterilized resting cysts (produced by sexual crosses of strain GCDE06 and strain GCLV01) and grown with: 1) complex bacterial communities derived from each of the two parent cultures; 2) simplified bacterial communities composed of the G. catenatum-associated bacteria Marinobacter sp. strain DG879 or Alcanivorax sp. strain DG881; 3) a complex bacterial community associated with an untreated, unsterilized sexual cross of the parents. Toxin content (STX-equivalent per cell) of clonal offspring (134-197 fmol STX cell(-1)) was similar to the parent cultures (169-206 fmol STX cell(-1)), however cultures grown with single bacterial types contained less toxin (134-146 fmol STX cell(-1)) than offspring or parent cultures grown with more complex mixed bacterial communities (152-176 fmol STX cell(-1)). Specific toxin production rate (fmol STX day(-1)) was strongly correlated with culture growth rate. Net toxin production rate (fmol STX cell(-1) day(-1)) did not differ among treatments, however, mean net toxin production rate of offspring was 8-fold lower than the parent cultures, suggesting that completion of the sexual lifecycle in laboratory cultures leads to reduced toxin production. The PST profiles of offspring cultures were most similar to parent GCDE06 with the exception of cultures grown with Marinobacter sp. DG879 which produced higher proportions of dcGTX2+3 and GC1+2, and lower proportions of C1+2 and C3+4. Our data demonstrate that the bacterial community can alter intracellular STX

  13. Discovery Of Human Antibodies Against Spitting Cobra Toxins

    DEFF Research Database (Denmark)

    Bojsen-Møller, Laura; Lohse, Brian; Harrison, Robert

    Current snakebite envenoming treatment options consist of animal-derived antisera and are associated with severe adverse reactions due to the heterologous nature of the animal-derived antibodies present in these antisera, and the presence of therapeutically irrelevant antibodies. The African...... spitting cobras are among the most medically important snakes in sub-Saharan regions due to the severity of the clinical outcomes caused by their cytotoxic venom, which is derived from cytotoxins of the 3FTx toxin family and PLA2. Here we report the results of our progress in identifying human antibodies...... targeting relevant toxins from the venom of the black necked spitting cobra (Naja nigricolis)....

  14. Palytoxin: a new marine toxin from a coelenterate.

    Science.gov (United States)

    Moore, R E; Scheuer, P J

    1971-04-30

    Palytoxin has been isolated from the zoanthids "limu-make-o-Hana" (Tentatively identified as Palythoa sp.) as a noncrystalline, chromatographically pure entity. Apart from polypeptide and protein toxins, it is the most highly toxic substance known, with a lethal dose (LD(59)) in mice of 0.15 microgram per kilogram by intravenous injection. Unlike the potent toxins batrachotoxin, saxitoxin, and tetrodotoxin which have molecular weights of 500 or less, palytoxin has an estimated molecular weight of 3300 and contains no repetitive amino acid or sugar units.

  15. Role of FODMAP content in enteral nutrition-associated diarrhea.

    Science.gov (United States)

    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.

  16. N-chlorotaurine, a long-lived oxidant produced by human leukocytes, inactivates Shiga toxin of enterohemorrhagic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Christian Eitzinger

    Full Text Available N-chlorotaurine (NCT, the main representative of long-lived oxidants produced by granulocytes and monocytes, is known to exert broad-spectrum microbicidal activity. Here we show that NCT directly inactivates Shiga toxin 2 (Stx2, used as a model toxin secreted by enterohemorrhagic Escherichia coli (EHEC. Bacterial growth and Stx2 production were both inhibited by 2 mM NCT. The cytotoxic effect of Stx2 on Vero cells was removed by ≥5.5 mM NCT. Confocal microscopy and FACS analyses showed that the binding of Stx2 to human kidney glomerular endothelial cells was inhibited, and no NCT-treated Stx2 entered the cytosol. Mass spectrometry displayed oxidation of thio groups and aromatic amino acids of Stx2 by NCT. Therefore, long-lived oxidants may act as powerful tools of innate immunity against soluble virulence factors of pathogens. Moreover, inactivation of virulence factors may contribute to therapeutic success of NCT and novel analogs, which are in development as topical antiinfectives.

  17. Special issue: engineering toxins for 21st-century therapies: introduction.

    Science.gov (United States)

    Acharya, K Ravi

    2011-12-01

    This special issue on 'Engineering toxins for 21st century therapies' provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products. © 2011 The Author Journal compilation © 2011 FEBS.

  18. Development of a quail embryo model for the detection of botulinum toxin type A activity

    Science.gov (United States)

    Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

  19. Structure–Activity Relationship Study of Spider Polyamine Toxins as Inhibitors of Ionotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Poulsen, Mette H; Hussein, Rama A

    2014-01-01

    The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only...

  20. Climate change impacts on natural toxins in food production systems, exemplified by deoxynivalenol in wheat and diarrhetic shellfish toxins

    DEFF Research Database (Denmark)

    van der Fels-Klerx, H J; Olesen, Jørgen E; Naustvoll, L-J

    2012-01-01

    Climate change is expected to affect food and feed safety, including the occurrence of natural toxins in primary crop and seafood production; however, to date, quantitative estimates are scarce. This study aimed to estimate the impact of climate change effects on mycotoxin contamination of cereal...... on food safety hazards, rather than median or average values only. Furthermore, it is recommended to closely monitor levels of mycotoxins and marine biotoxins in the future, in particular related to risky situations associated with favourable climatic conditions for toxin producing organisms...

  1. Cholera Toxin Induces Sustained Hyperexcitability in Myenteric, but Not Submucosal, AH Neurons in Guinea Pig Jejunum

    Directory of Open Access Journals (Sweden)

    Joel C. Bornstein

    2017-04-01

    Full Text Available Background and Aims: Cholera toxin (CT-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS. AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs, are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons.Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX in their lumen. After washing CT away, submucosal or myenteric plexus preparations were dissected keeping circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was monitored by injecting 500 ms current pulses through the recording electrode.Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to intact mucosa (n = 29 was greater than that of control neurons (n = 24, but submucosal AH neurons (n = 33, control n = 27 were unaffected. CT also induced excitability increases in myenteric AH neurons impaled distant from the mucosa (n = 6 or in its absence (n = 5. Coincubation with tetrodotoxin or SR142801 (NK3 receptor antagonist, but not SR140333 (NK1 antagonist or granisetron (5-HT3 receptor antagonist prevented the increased excitability induced by CT. Increased excitability was associated with a reduction in the characteristic AHP and an increase in the ADP of these neurons, but not a change in the hyperpolarization-activated inward current, Ih.Conclusions: CT increases excitability of myenteric, but not submucosal, AH neurons. This is neurally mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to amplify the secretomotor response to CT via an increase in the

  2. Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test.

    Science.gov (United States)

    Yu, Fang Fang; Lin, Xia Lu; Yang, Lei; Liu, Huan; Wang, Xi; Fang, Hua; Lammi, ZMikko J; Guo, Xiong

    2017-11-01

    Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  3. Implementation of enteral feeding protocol in an intensive care unit

    DEFF Research Database (Denmark)

    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

    Science.gov (United States)

    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

    Science.gov (United States)

    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

    KAUST Repository

    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. Bordetella adenylate cyclase toxin: a swift saboteur of host defense

    Czech Academy of Sciences Publication Activity Database

    Vojtová, Jana; Kamanová, Jana; Šebo, Peter

    2006-01-01

    Roč. 9, - (2006), s. 1-7 ISSN 1369-5274 R&D Projects: GA AV ČR IAA5020406; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50200510 Keywords : cyaa * scanning electron microscopy * cyclase toxin Subject RIV: EE - Microbiology, Virology Impact factor: 7.445, year: 2006

  8. Discovery of human antibodies against black cobra toxins

    DEFF Research Database (Denmark)

    Øhlenschlæger, Mia; Andersen, Mikael Rørdam; Lohse, Brian

    Snakebite envenoming represents a major health threat intropical parts of the developing world1. Animal-derivedantisera currently constitute the only effective treatment option,but are associated with severe side effects due toincompatibility with the human immune system. We aim atdiscovering hum...... antibodies that target the medically mostimportant toxins from N. melanoleuca venom using phagedisplay technology....

  9. Sterol-specific membrane interactions with the toxins from ...

    African Journals Online (AJOL)

    The lipophilic toxins from Karlodinium micrum, KmTX, have negative effects on several co-occurring phytoplankton species, yet appear to have no effect on K. micrum itself. One of these compounds, KmTX2, has differing toxicity towards eukaryotic membranes with differing sterol compositions (vertebrate > fungal ...

  10. Effect of Cryphonectria parasitica toxin on lipid peroxidation and ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... African Journal of Biotechnology Vol. 10(65) ... on membrane systems of the cells were lighter and they occurred later than expected in the resistant ..... Starch was accumulated normally in chloroplasts after Cp-toxin treatment and the starch inclusions continued to enlarge in all stages of treated leaves cells ...

  11. Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

    Directory of Open Access Journals (Sweden)

    Badshah Syed Lal

    2016-01-01

    Full Text Available A molecular dynamics (MD simulation study of the enzymatic portion of cholera toxin; cholera toxin A-1 polypeptide (CTA1 was performed at 283, 310 and 323 K. From total energy analysis it was observed that this toxin is stable thermodynamically and these outcomes were likewise confirmed by root mean square deviations (RMSD investigations. The Cα root mean square fluctuation (RMSF examinations revealed that there are a number of residues inside CTA1, which can be used as target for designing and synthesizing inhibitory drugs, in order to inactivate cholera toxin inside the human body. The fluctuations in the radius of gyration and hydrogen bonding in CTA1 proved that protein unfolding and refolding were normal routine phenomena in its structure at all temperatures. Solvent accessible surface area study identified the hydrophilic nature of the CTA1, and due to this property it can be a potential biological weapon. The structural identification (STRIDE algorithm for proteins was successfully used to determine the partially disordered secondary structure of CTA1. On account of this partially disordered secondary structure, it can easily deceive the proteolytic enzymes of the endoplasmic reticulum of host cells.

  12. Cyanobacterial toxins: A short review on phytotoxic effect in an ...

    African Journals Online (AJOL)

    Cyanobacteria are photosynthetic prokaryotes which frequently form blooms in eutrophic water bodies. Some species of cyanobacteria are able to produce toxins (cyanotoxins) that can cause aquatic environment and diverse organisms living there to be at a serious risk. One of the more serious impacts of eutrophication on ...

  13. An Overview of Helicobacter pylori VacA Toxin Biology

    Science.gov (United States)

    Foegeding, Nora J.; Caston, Rhonda R.; McClain, Mark S.; Ohi, Melanie D.; Cover, Timothy L.

    2016-01-01

    The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease. PMID:27271669

  14. High-throughput epitope profiling of snake venom toxins

    DEFF Research Database (Denmark)

    Engmark, Mikael; Andersen, Mikael Rørdam; Laustsen, Andreas Hougaard

    Insight into the molecular details of polyclonal antivenom antibody specificity is a prerequisite for accurate prediction of cross-reactivity and can provide a basis for design of novel antivenoms. In this work, a highthroughput approach was applied to characterize linear elements in epitopes in ...... toxins from four African mamba and three neurotoxic cobra snakes obtained from public databases....

  15. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    Expression and purification of recombinant Shiga toxin 2B from Escherichia coli O157:H7. ... (SDS-PAGE) and StxB2 yield was 450 μg ml-1 confirmed by Bradford assay. Recombinant Stx2B protein was produced in highly pure yield using ...

  16. Bacterial toxin-antitoxin systems: more than selfish entities?

    Directory of Open Access Journals (Sweden)

    Laurence Van Melderen

    2009-03-01

    Full Text Available Bacterial toxin-antitoxin (TA systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.

  17. Breakthrough of Oscillatoria limnetica and microcystin toxins into ...

    African Journals Online (AJOL)

    The presence of cyanobacteria and their toxins (cyanotoxins) in processed drinking water may pose a health risk to humans and animals. The efficiency of conventional drinking water treatment processes (coagulation, flocculation, rapid sand filtration and disinfection) in removing cyanobacteria and cyanotoxins varies ...

  18. Centrifugal microfluidic platform for ultrasensitive detection of Botulinum Toxin

    Science.gov (United States)

    Botulinum neurotoxin – a global public health threat and category A bioterrorism agent - is the most toxic substance known and one of the most challenging toxins to detect due to its lethality at extremely low concentrations. Hence the live-mouse bioassay because of its superior sensitivity, remains...

  19. Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

    Science.gov (United States)

    Disease pathways form overlapping networks, and hub proteins represent attractive targets for broad-spectrum drugs. Using bacterial toxins as a proof of concept, we describe a new approach of discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pa...

  20. Investigation of inactivation of Clostridium botulinum toxin by nuclear radiation

    International Nuclear Information System (INIS)

    Kaltenhaeuser, A.; Werner, K.H.

    1989-01-01

    The effect of nuclear radiation on the toxicity and the molecular structure of the toxin produced by the microorganism Clostridium botulinum type A was investigated. The radiation induced changes in the structure of the toxin molecule. This effect is influenced by the composition or the medium above the toxin solution as well as by the temperature during the irradiation. The results of the investigation indicate that with increasing irradiation dose a new molecule was formed with immunological properties similar to the properties of the original molecule however with a greater molecular weight. After exposure to a radiation dose of 3,4 Mrad at normal temperature in air, complete detoxification of the substance was found. Immunizing experiments with the toxoid with two guinea-pigs indicated a pronounced increase of the antibody titer in the serum after 4 weeks. Vaccination experiments with the toxoid on animals show, that the protection against the effect of the toxin corresponds to the demands of the European Pharmacopoeia. The efficiency of the toxoid shows a similar efficiency as toxoids produced by chemical methods. The production of a toxoid-viccine with the relatively simple method of nuclear radiation appears possible. (orig./MG) With 12 refs., 3 tabs., 11 figs [de

  1. Regulations for marine microalgal toxins: Towards harmonization of ...

    African Journals Online (AJOL)

    The World Trade Organization and the General Agreements on Tariffs and Trade encourage the harmonization of regulations on food safety requirements. The current policy on trade liberalization of seafood is presented, together with a review of the regulations for marine microalgal toxins. Activities on harmonization of ...

  2. Prevalence and antimicrobial sensitivity of Shiga-toxin-producing ...

    African Journals Online (AJOL)

    Background: Escherichia coli is among the most common causes of diarrhoea in children below five years of age in developing countries. Diarrhoeal diseases rank the second most common cause of morbidity and mortality in developing countries. Here we report the magnitude of Shiga toxin-producing Escherichia coli ...

  3. The cyanobacteria toxins, microcystins – emerging risks to human health

    Science.gov (United States)

    Dialysis patients appear to be at increased risk for exposure to cyanobacteria toxins; episodes of microcystin (MCYST) exposure via dialysate during 1996 and 2001 have been previously reported. During 2001, as many as 44 renal insufficiency patients were exposed to contaminated d...

  4. Yessotoxins, a Group of Marine Polyether Toxins: an Overview

    Directory of Open Access Journals (Sweden)

    José J. Fernández

    2008-05-01

    Full Text Available Yessotoxin (YTX is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA and dinophyisistoxin-1 (DTX-1, YTXs do not cause either diarrhea or inhibition of protein phosphatases . In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs.

  5. Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells.

    Science.gov (United States)

    Martín, César; Etxaniz, Asier; Uribe, Kepa B; Etxebarria, Aitor; González-Bullón, David; Arlucea, Jon; Goñi, Félix M; Aréchaga, Juan; Ostolaza, Helena

    2015-09-08

    Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca(2+)-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

  6. A Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin

    Science.gov (United States)

    2006-08-10

    Doyle, L.R. Beuchat, T.J. Montville (Eds.), Food Microbiology : Fundamentals and Fron- tiers, Second ed., ASM Press, Washington, D.C., 2001, pp. 351...D.E. Lorant, A.E. Bryant, G.A. Zimmerman, T.M. McIn- tyre, D.L. Stevens, S.M. Prescott , Alpha toxin from Clostridium per- fringens induces

  7. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    Science.gov (United States)

    Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  8. Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

    Science.gov (United States)

    Förstner, Philip; Bayer, Fabienne; Kalu, Nnanya; Felsen, Susanne; Förtsch, Christina; Aloufi, Abrar; Ng, David Y W; Weil, Tanja; Nestorovich, Ekaterina M; Barth, Holger

    2014-07-14

    Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.

  9. Structure of a bacterial toxin-activating acyltransferase.

    Science.gov (United States)

    Greene, Nicholas P; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

    2015-06-09

    Secreted pore-forming toxins of pathogenic Gram-negative bacteria such as Escherichia coli hemolysin (HlyA) insert into host-cell membranes to subvert signal transduction and induce apoptosis and cell lysis. Unusually, these toxins are synthesized in an inactive form that requires posttranslational activation in the bacterial cytosol. We have previously shown that the activation mechanism is an acylation event directed by a specialized acyl-transferase that uses acyl carrier protein (ACP) to covalently link fatty acids, via an amide bond, to specific internal lysine residues of the protoxin. We now reveal the 2.15-Å resolution X-ray structure of the 172-aa ApxC, a toxin-activating acyl-transferase (TAAT) from pathogenic Actinobacillus pleuropneumoniae. This determination shows that bacterial TAATs are a structurally homologous family that, despite indiscernible sequence similarity, form a distinct branch of the Gcn5-like N-acetyl transferase (GNAT) superfamily of enzymes that typically use acyl-CoA to modify diverse bacterial, archaeal, and eukaryotic substrates. A combination of structural analysis, small angle X-ray scattering, mutagenesis, and cross-linking defined the solution state of TAATs, with intermonomer interactions mediated by an N-terminal α-helix. Superposition of ApxC with substrate-bound GNATs, and assay of toxin activation and binding of acyl-ACP and protoxin peptide substrates by mutated ApxC variants, indicates the enzyme active site to be a deep surface groove.

  10. Susceptibility of Phelipanche and Orobanche species to AAL-toxin.

    Science.gov (United States)

    de Zélicourt, Axel; Montiel, Grégory; Pouvreau, Jean-Bernard; Thoiron, Séverine; Delgrange, Sabine; Simier, Philippe; Delavault, Philippe

    2009-10-01

    Fusarium and Alternaria spp. are phytopathogenic fungi which are known to be virulent on broomrapes and to produce sphinganine-analog mycotoxins (SAMs). AAL-toxin is a SAM produced by Alternaria alternata which causes the inhibition of sphinganine N-acyltransferase, a key enzyme in sphingolipid biosynthesis, leading to accumulation of sphingoid bases. These long chain bases (LCBs) are determinant in the occurrence of programmed cell death (PCD) in susceptible plants. We showed that broomrapes are sensitive to AAL-toxin, which is not common plant behavior, and that AAL-toxin triggers cell death at the apex of the radicle as well as LCB accumulation and DNA laddering. We also demonstrated that three Lag1 homologs, encoding components of sphinganine N-acyltransferase in yeast, are present in the Orobanche cumana genome and two of them are mutated leading to an enhanced susceptibility to AAL-toxin. We therefore propose a model for the molecular mechanism governing broomrape susceptibility to the fungus Alternaria alternata.

  11. Freshwater Cyanobacteria (Blue-Green Algae) Toxins: Isolation and Characterization

    Science.gov (United States)

    1985-10-01

    These toxins have caused loss of cattle and wild animals, due to the consumption of the contami- nated water and the bloom mass, in several countries...of American Association of Anatomists, Miami, 1979. Koenig, H. and Dabholkar, A.S.: Rapid effects of testosterone, pilocarpine and castration in rat

  12. The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis

    DEFF Research Database (Denmark)

    Mortensen, Ninell P; Schiellerup, Peter; Boisen, Nadia

    2011-01-01

    The role of Campylobacter jejuni cytolethal distending toxin (CDT) on clinical outcome after gastroenteritis was investigated. Clinical data, blood serum samples, and Campylobacter spp. isolated, from each of 30 patients were collected over a period of 6 months. The CDT encoding genes, cdt...

  13. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    sunny t

    2016-05-25

    May 25, 2016 ... MATERIALS AND METHODS. Bacterial strains, plasmid and media ... toxin 2B gene after purified by wizard genomic DNA purification kit. (Promega, USA) ..... This result was approximately two times higher compared to Halo .... manual, 3rd Eds. New York: Cold Spring Harbor Laboratory Press,. Cold Spring ...

  14. Shiga Toxin (Stx) Gene Detection and Verotoxigenic Potentials of ...

    African Journals Online (AJOL)

    Non-0157 Escherichia coli, isolated from Nono (fermented fresh cow milk) sampled from four major Nigerian cities, namely, Abuja, Benin City, Lagos and Onitsha were investigated for the presence shiga toxins (stx1 and stx2) genes using PCR technique and for their verotoxigenic potentials using tissue culture assay on ...

  15. 9 CFR 121.4 - Overlap select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ... in paragraph (b) of this section that have been genetically modified. (d) Overlap select agents or... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE... elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce...

  16. Longitudinal Phonatory Characteristics after Botulinum Toxin Type A Injection.

    Science.gov (United States)

    Fisher, Kimberly V.; And Others

    1996-01-01

    A study investigated the long-term effects of a Botulinum Toxin Type A injection on the glottal competency of a man with adductor spasmodic dysphonia. Results suggest that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. (CR)

  17. Phenol-Soluble Modulin Toxins of Staphylococcus haemolyticus

    Directory of Open Access Journals (Sweden)

    Fei Da

    2017-05-01

    Full Text Available Coagulase-negative staphylococci (CoNS are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, after Staphylococcus epidermidis, is Staphylococcus haemolyticus. However, we have a significant lack of knowledge about what causes virulence of S. haemolyticus, as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogen Staphylococcus aureus, toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs, amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other than S. epidermidis. Here, we identified, purified, and characterized PSMs of S. haemolyticus. We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed that S. haemolyticus does not produce a δ-toxin, as results from genome sequencing had indicated. All four S. haemolyticus PSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM, S. haemolyticus PSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis.

  18. Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

    NARCIS (Netherlands)

    Mantzouki, Evanthia; Lürling, Miquel; Fastner, Jutta; de Senerpont Domis, Lisette; Wilk-Woźniak, Elżbieta; Koreivienė, Judita; Seelen, Laura; Teurlincx, Sven; Verstijnen, Yvon; Krztoń, Wojciech; Walusiak, Edward; Karosienė, Jūratė; Kasperovičienė, Jūratė; Savadova, Ksenija; Vitonytė, Irma; Cillero-Castro, Carmen; Budzyńska, Agnieszka; Goldyn, Ryszard; Kozak, Anna; Rosińska, Joanna; Szeląg-Wasielewska, Elżbieta; Domek, Piotr; Jakubowska-Krepska, Natalia; Kwasizur, Kinga; Messyasz, Beata; Pełechaty, Aleksandra; Pełechaty, Mariusz; Kokocinski, Mikolaj; García-Murcia, Ana; Real, Monserrat; Romans, Elvira; Noguero-Ribes, Jordi; Duque, David Parreño; Fernández-Morán, Elísabeth; Karakaya, Nusret; Häggqvist, Kerstin; Demir, Nilsun; Beklioğlu, Meryem; Filiz, Nur; Levi, Eti E.; Iskin, Uğur; Bezirci, Gizem; Tavşanoğlu, Ülkü Nihan; Özhan, Koray; Gkelis, Spyros; Panou, Manthos; Fakioglu, Özden; Avagianos, Christos; Kaloudis, Triantafyllos; Çelik, Kemal; Yilmaz, Mete; Marcé, Rafael; Catalán, Nuria; Bravo, Andrea G.; Buck, Moritz; Colom-Montero, William; Mustonen, Kristiina; Pierson, Don; Yang, Yang; Raposeiro, Pedro M.; Gonçalves, Vítor; Antoniou, Maria G.; Tsiarta, Nikoletta; McCarthy, Valerie; Perello, Victor C.; Feldmann, Tõnu; Laas, Alo; Panksep, Kristel; Tuvikene, Lea; Gagala, Ilona; Mankiewicz-Boczek, Joana; Yağcı, Meral Apaydın; Çınar, Şakir; Çapkın, Kadir; Yağcı, Abdulkadir; Cesur, Mehmet; Bilgin, Fuat; Bulut, Cafer; Uysal, Rahmi; Obertegger, Ulrike; Boscaini, Adriano; Flaim, Giovanna; Salmaso, Nico; Cerasino, Leonardo; Richardson, Jessica; Visser, Petra M; Verspagen, Jolanda M. H.; Karan, Tünay; Soylu, Elif Neyran; Maraşlıoğlu, Faruk; Napiórkowska-Krzebietke, Agnieszka; Ochocka, Agnieszka; Pasztaleniec, Agnieszka; Antão-Geraldes, Ana M.; Vasconcelos, Vitor; Morais, João; Vale, Micaela; Köker, Latife; Akçaalan, Reyhan; Albay, Meriç; Špoljarić Maronić, Dubravka; Stević, Filip; Žuna Pfeiffer, Tanja; Fonvielle, Jeremy; Straile, Dietmar; Rothhaupt, Karl-Otto; Hansson, Lars-Anders; Urrutia-Cordero, Pablo; Bláha, Luděk; Geriš, Rodan; Fránková, Markéta; Koçer, Mehmet Ali Turan; Alp, Mehmet Tahir; Remec-Rekar, Spela; Elersek, Tina; Triantis, Theodoros; Zervou, Sevasti-Kiriaki; Hiskia, Anastasia; Haande, Sigrid; Skjelbred, Birger; Madrecka, Beata; Nemova, Hana; Drastichova, Iveta; Chomova, Lucia; Edwards, Christine; Sevindik, Tuğba Ongun; Tunca, Hatice; Önem, Burçin; Aleksovski, Boris; Krstić, Svetislav; Vucelić, Itana Bokan; Nawrocka, Lidia; Salmi, Pauliina; Machado-Vieira, Danielle; de Oliveira, Alinne Gurjão; Delgado-Martín, Jordi; García-García, David; Cereijo, Jose Luís; Gomà, Joan; Trapote, Mari Carmen; Vegas-Vilarrúbia, Teresa; Obrador, Biel; Grabowska, Magdalena; Karpowicz, Maciej; Chmura, Damian; Úbeda, Bárbara; Gálvez, José Ángel; Özen, Arda; Christoffersen, Kirsten Seestern; Warming, Trine Perlt; Kobos, Justyna; Mazur-Marzec, Hanna; Pérez-Martínez, Carmen; Ramos-Rodríguez, Eloísa; Arvola, Lauri; Alcaraz-Párraga, Pablo; Toporowska, Magdalena; Pawlik-Skowronska, Barbara; Niedźwiecki, Michał; Pęczuła, Wojciech; Leira, Manel; Hernández, Armand; Moreno-Ostos, Enrique; Blanco, José María; Rodríguez, Valeriano; Montes-Pérez, Jorge Juan; Palomino, Roberto L.; Rodríguez-Pérez, Estela; Carballeira, Rafael; Camacho, Antonio; Picazo, Antonio; Rochera, Carlos; Santamans, Anna C.; Ferriol, Carmen; Romo, Susana; Soria, Juan Miguel; Dunalska, Julita; Sieńska, Justyna; Szymański, Daniel; Kruk, Marek; Kostrzewska-Szlakowska, Iwona; Jasser, Iwona; Žutinić, Petar; Gligora Udovič, Marija; Plenković-Moraj, Anđelka; Frąk, Magdalena; Bańkowska-Sobczak, Agnieszka; Wasilewicz, Michał; Özkan, Korhan; Maliaka, Valentini; Kangro, Kersti; Grossart, Hans-Peter; Paerl, Hans W.; Carey, Cayelan C.; Ibelings, Bas W.

    2018-01-01

    Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and

  19. Experience with botulinum toxin in the treatment of cerebral palsy

    African Journals Online (AJOL)

    Institute of Child Health, Red Cross War Memorial Children's. Hospital and University of .... A majority of the children in this study showed definite short- term benefit following botulinum toxin injection and this form of therapy constitutes ... repeated when necessary as long as the spasticity remains dynamic. Patients with ...

  20. Bupivacaine and botulinum toxin to treat comitant strabismus

    Directory of Open Access Journals (Sweden)

    Luisa Moreira Hopker

    2012-04-01

    Full Text Available PURPOSE: To evaluate the change in ocular motility and muscle thickness measured with ultrasonography after intramuscular injection of bupivacaine and botulinum toxin A. METHODS: Eight patients (five female were enrolled to measure ocular motility prior and 1, 7, 30 and 180 days after one injection of 2 ml of 1.5% bupivacaine and 2.5 U of botulinum toxin A in agonist and antagonist muscles, respectively, of eight amblyopic eyes. Muscle thickness was measured prior and on days 1, 7 and 30 after injection using 10-MHz ultrasonography (eyelid technique. RESULTS: Mean change in alignment was 10 prism diopters after 180 days (n=6. An average increase of 1.01 mm in muscle thickness was observed after 30 days of bupivacaine injection and 0.28 mm increase was observed after botulinum toxin A injection, as measured by ultrasonography. Lateral rectus muscles injected with bupivacaine had a mean increase of 1.5 mm in muscle thickness. CONCLUSION: In this study, a change in ocular motility was observed after 180 days of intramuscular injection of bupivacaine and botulinum toxin in horizontal extraocular muscles. Overall, there was an increase of muscle thickness in both botulinum toxinum A and bupivacaine injected muscles after 30 days of injection when measured by ultrasonography. This change was more pronounced on lateral rectus muscles after bupivacaine injection.