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Sample records for pertussis toxin treatment

  1. 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.

  2. Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes

    International Nuclear Information System (INIS)

    Luttrell, L.M.; Hewlett, E.L.; Romero, G.; Rogol, A.D.

    1988-01-01

    The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 mycocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [ 32 P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [ 3 H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [ 3 H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin

  3. Contribution of pertussis toxin to the pathogenesis of pertussis disease

    Science.gov (United States)

    Carbonetti, Nicholas H.

    2015-01-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

  4. Pertussis toxin treatment of whole blood. A novel approach to assess G protein function in congestive heart failure

    NARCIS (Netherlands)

    Maisel, A. S.; Michel, M. C.; Insel, P. A.; Ennis, C.; Ziegler, M. G.; Phillips, C.

    1990-01-01

    This study was designed to assess G protein function in mononuclear leukocytes (MNL) of patients with congestive heart failure (CHF). MNL membranes were ADP-ribosylated in vitro in the presence of pertussis or cholera toxin. The amount of pertussis toxin substrates did not differ significantly

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

    International Nuclear Information System (INIS)

    Yamashita, N.; Kojima, I.; Shibuya, N.; Ogata, E.

    1987-01-01

    The effect of pertussis toxin on somatostatin-induced K + current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K + current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K + , Na + , and Ca 2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [ 32 P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment

  10. Pertussis leukocytosis: mechanisms, clinical relevance and treatment

    Science.gov (United States)

    Carbonetti, Nicholas H.

    2016-01-01

    The significant and sometimes dramatic rise in the number of circulating white blood cells (leukocytosis) in infants suffering from pertussis (whooping cough) has been recognized for over a century. Although pertussis is a disease that afflicts people of all ages, it can be particularly severe in young infants, and these are the individuals in whom leukocytosis is most pronounced. Very high levels of leukocytosis are associated with poor outcome in infants hospitalized with pertussis and modern treatments are often aimed at reducing the number of leukocytes. Pertussis leukocytosis is caused by pertussis toxin, a soluble protein toxin released by Bordetella pertussis during infection, but the exact mechanisms by which this occurs are still unclear. In this minireview, I discuss the history of clinical and experimental findings on pertussis leukocytosis, possible contributing mechanisms causing this condition and treatments aimed at reducing leukocytosis in hospitalized infants. Since recent studies have detailed significant associations between specific levels of pertussis leukocytosis and fatal outcome, this is a timely review that may stimulate new thinking on how to understand and combat this problem. PMID:27609461

  11. ADP-ribosylation of transducin by pertussis toxin

    International Nuclear Information System (INIS)

    Watkins, P.A.; Burns, D.L.; Kanaho, Y.; Liu, T.Y.; Hewlett, E.L.; Moss, J.

    1985-01-01

    Transducin, the guanyl nucleotide-binding regulatory protein of retinal rod outer segments that couples the photon receptor, rhodopsin, with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, T alpha and T beta gamma. T alpha (39 kDa), which is [ 32 P]ADP-ribosylated by pertussis toxin and [ 32 P]NAD in rod outer segments and in purified transducin, was also labeled by the toxin after separation from T beta gamma (36 kDa and approximately 10 kDa); neither component of T beta gamma was a pertussis toxin substrate. Labeling of T alpha was enhanced by T beta gamma and was maximal at approximately 1:1 molar ratio of T alpha : T beta gamma. Limited proteolysis by trypsin of T alpha in the presence of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) resulted in the sequential appearance of proteins of 38 and 32 kDa. The amino terminus of both 38- and 32 -kDa proteins was leucine, whereas that of T alpha could not be identified and was assumed to be blocked. The 32 -kDa peptide was not a pertussis toxin substrate. Labeling of the 38-kDa protein was poor and was not enhanced by T beta gamma. Trypsin treatment of [ 32 P]ADP-ribosyl-T alpha produced a labeled 37-38-kDa doublet followed by appearance of radioactivity at the dye front. It appears, therefore, that, although the 38-kDa protein was poor toxin substrate, it contained the ADP-ribosylation site. Without rhodopsin, labeling of T alpha (in the presence of T beta gamma) was unaffected by Gpp(NH)p, guanosine 5'-O-(thiotriphosphate) (GTP gamma S), GTP, GDP, and guanosine 5'-O-(thiodiphosphate) (GDP beta S) but was increased by ATP. When photolyzed rhodopsin and T beta gamma were present, Gpp(NH)p and GTP gamma S decreased [ 32 P]ADP-ribosylation by pertussis toxin. Thus, pertussis toxin-catalyzed [ 32 P]ADP-ribosylation of T alpha was affected by nucleotides, rhodopsin and light in addition to T beta gamma

  12. Pertussis Diagnosis & Treatment

    Science.gov (United States)

    ... in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & Epidemiology Materials ... been exposed to pertussis and by doing a: History of typical signs and symptoms Physical examination Laboratory ...

  13. The effect of pertussis toxin (PTX) treatment on blood pressure (BP), norepinephrine pressor responsiveness and BP response to acute nifedipine administration in genetic hypertension

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 48, č. 4 (2006), s. 773-774 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] R&D Projects: GA MZd(CZ) NR7786 Keywords : pertussis toxin * blood pressure * norepinephrine * nifedipine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  14. Pertussis toxin treatment does not block inhibition by atrial natriuretic factor of aldosterone secretion in cultured bovine zona glomerulosa cells

    International Nuclear Information System (INIS)

    De Lean, A.; Cantin, M.

    1986-01-01

    The authors have previously reported that atrial natriuretic factor (ANF) potently inhibits PGE or forskolin-stimulation aldosterone secretion in bovine zona glomerulosa (ZG) by acting through specific high affinity receptors. In order to evaluate the functional role of the regulatory protein N/sub i/ and the inhibition of adenylate cyclase activity (AC) in ZG, the authors have studied the effect of treatment with PT on inhibition by ANF of aldosterone production. Primary cultures of ZG were treated for 18 hours in serum-free F12 medium with (0-100 ng/ml PT). No effect of PT pretreatment was observed either on basal, PGE-stimulated or ANF-inhibited levels of steroidogenesis. When membranes prepared from control ZG were ADP-ribosylated with [ 32 P] NAD in the presence of PT, two toxin-specific bands with 39 Kd and 41 Kd were documented on SDS gel. Cell pretreatment with as low as 1 ng/ml drastically reduced further labelling of these two bands while higher doses completely abolished them. Since PT treatment covalently modifies completely the toxin substrate without altering ANF inhibition of adrenal steroidogenesis, the authors conclude that N/sub i/ is not involved in the mode of action of ANF on aldosterone production

  15. [Production of pertussis toxin by Bordetella pertussis strains isolated from patients with whooping cough].

    Science.gov (United States)

    Zaĭtsev, E M; Mertsalova, N U; Shinkarev, A S; Mazurova, I K; Zakharova, N S

    2011-01-01

    To assess level of pertussin toxin (PT) production by vaccine strains of Bordetella pertussis and strains isolated from patients with whooping cough. Concentration of PT in supernatants of microbial cultures of 3 vaccine strains and 25 strains of B. pertussis isolated from patients with pertussis in 2001 - 2005 was measured with enzyme immunoassay using gamma-globulin fractions of rabbit antiserum to PT as immunosorbent or included in peroxidase conjugates. Level of PT production by strains isolated from infected persons varied from 3 +/- 0.5 to 64.8 +/- 12.2 ng/MFU/ml: in 9 strains--from 3 +/- 0.5 to 9.4 +/- 2.1 ng/MFU/ml, in 7--10.5 +/- 1.8 to 18.4 +/- 2.6 ng/MFU/ml, and in 9--23.6 +/- 4.5 to 64.8 +/- 12.2 ng/MFU/ml. B. pertussis strains isolated from patients were heterogeneous on level of PT production. Difference in expression of PT between strains were as high as 20-fold. Conditionally low, moderate and high levels of PT production had 9 (36%), 7 (28%), and 9 (36%) of 25 studied strains. Three vaccine strains had levels of toxin production similar to recently isolated strains with moderate level of its production.

  16. Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

    Czech Academy of Sciences Publication Activity Database

    Šebo, Peter; Osička, Radim; Mašín, Jiří

    2014-01-01

    Roč. 13, č. 10 (2014), s. 1215-1227 ISSN 1476-0584 R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : adenylate cyclase toxin * antigen delivery * Bordetella pertussis Subject RIV: EE - Microbiology, Virology Impact factor: 4.210, year: 2014

  17. The effects of pertussis toxin-treatment on integrated vasoactive response of vascular system in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Čačányiová, S.; Kristek, F.; Kuneš, Jaroslav; Zicha, Josef

    2008-01-01

    Roč. 57, č. 1 (2008), s. 137-139 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6139/27 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertusis toxin * blood pressure * SHR Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  18. Pertussis: Microbiology, Disease, Treatment, and Prevention

    Science.gov (United States)

    Salim, Abdulbaset M.; Zervos, Marcus J.; Schmitt, Heinz-Josef

    2016-01-01

    SUMMARY Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. PMID:27029594

  19. Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells

    International Nuclear Information System (INIS)

    Mahy, N.; Woolkalis, M.; Thermos, K.; Carlson, K.; Manning, D.; Reisine, T.

    1988-01-01

    The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog [125I]CGP 23996. [125I]CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity [125I]CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of [125I]CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect [125I]CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with [125I] CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to [125I]CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors

  20. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

    Science.gov (United States)

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-02

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. Copyright © 2015, American Association for the Advancement of Science.

  1. Purification of heat labile toxin from Bordetella pertussis vaccine ...

    African Journals Online (AJOL)

    . pertussis vaccine strain 134 by employing indigenous technology and examining the immuno-biochemical aspects of the purified protein. Materials and methods: Shaker cultivation of B. pertussis strain 134, sterility, opacity confirmation, TCA ...

  2. Pertussis toxins, other antigens become likely targets for genetic engineering

    Energy Technology Data Exchange (ETDEWEB)

    Marwick, C.

    1990-11-14

    Genetically engineered pertussis vaccines have yet to be fully tested clinically. But early human, animal, and in vitro studies indicate effectiveness in reducing toxic effects due to Bordetella pertussis. The licensed pertussis vaccines consists of inactivated whole cells of the organism. Although highly effective, they have been associated with neurologic complications. While the evidence continues to mount that these complications are extremely rare, if they occur at all, it has affected the public's acceptance of pertussis immunization.

  3. Reconstitution of high affinity α2 adrenergic agonist binding by fusion with a pertussis toxin substrate

    International Nuclear Information System (INIS)

    Kim, M.H.; Neubig, R.R.

    1986-01-01

    High affinity α 2 adrenergic agonist binding is thought to occur via a coupling of the α 2 receptor with N/sub i/, the inhibitory guanyl nucleotide binding protein. Human platelet membranes pretreated at pH 11.5 exhibit a selective inactivation of agonist binding and N/sub i/. To further study the mechanism of agonist binding, alkali treated membranes (ATM) were mixed with membranes pretreated with 10 μM phenoxybenzamine to block α 2 receptors (POB-M). The combined membrane pellet was incubated in 50% polyethylene glycol (PEG) to promote membrane-membrane fusion and assayed for binding to the α 2 agonist [ 3 H]UK 14,304 (UK) and the antagonist [ 3 H] yohimbine. PEG treatment resulted in a 2-4 fold enhancement of UK binding whereas yohimbine binding was unchanged. No enhancement of UK binding was observed in the absence of PEG treatment. The reconstitution was dependent on the addition of POB-M. They found that a 1:1 ratio of POB-M:ATM was optimal. Reconstituted binding was inhibited by GppNHp. Fusion of rat C6 glioma cell membranes, which do not contain α 2 receptors, also enhanced agonist binding to ATM. Fusion of C6 membranes from cells treated with pertussis toxin did not enhance [ 3 H] UK binding. These data show that a pertussis toxin sensitive membrane component, possibly N/sub i/, can reconstitute high affinity α 2 agonist binding

  4. ADP-ribosylation of membrane components by pertussis and cholera toxin

    International Nuclear Information System (INIS)

    Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.; Codina, J.; Field, J.B.; Birnbaumer, L.; Sekura, R.D.

    1985-01-01

    Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its α/sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its α; subunit. By using [ 32 P]NAD + and determining the transfer of its [ 32 P]ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/sub s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin

  5. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence.

    NARCIS (Netherlands)

    Mooi, F.R.; Loo, I.H. van; Gent, M. van; He, Q.; Bart, M.J.; Heuvelman, K.J.; Greeff, S.C. de; Diavatopoulos, D.A.; Teunis, P.; Nagelkerke, N.; Mertsola, J.

    2009-01-01

    Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated

  6. Effect of different forms of adenylate cyclase toxin of Bordetella pertussis on protection afforded by an acellular pertussis vaccine in a murine model.

    Science.gov (United States)

    Cheung, Gordon Y C; Xing, Dorothy; Prior, Sandra; Corbel, Michael J; Parton, Roger; Coote, John G

    2006-12-01

    Four recombinant forms of the cell-invasive adenylate cyclase toxin (CyaA) of Bordetella pertussis were compared for the ability to enhance protection against B. pertussis in mice when coadministered with an acellular pertussis vaccine (ACV). The four forms were as follows: fully functional CyaA, a CyaA form lacking adenylate cyclase enzymatic activity (CyaA*), and the nonacylated forms of these toxins, i.e., proCyaA and proCyaA*, respectively. None of these forms alone conferred significant (P > 0.05) protection against B. pertussis in a murine intranasal challenge model. Mice immunized with ACV alone showed significant (P protection was only significant (P protection provided by CyaA* was due to an augmentation of both Th1 and Th2 immune responses to B. pertussis antigens.

  7. Pertussis.

    NARCIS (Netherlands)

    Maas, N.A.T. van der; Kemmeren, J.M.; Lugner, A.K.; Suijkerbuijk, A.W.M.; Donker, G.A.; Buisman, A.; Berbers, G.A.M.; Els, C.A.C.M. van; Melker, H.E. de; Mooi, F.R.

    2014-01-01

    In 2012, a large pertussis epidemic occurred with the highest number of notified cases since the introduction of notifications in 1976. Data on GP consultations and hospitalisations from 2012 also showed an increase. In the first six months of 2013 the incidence of pertussis notifications was found

  8. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    Energy Technology Data Exchange (ETDEWEB)

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. (Medical College of Wisconsin, Milwaukee (USA))

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  9. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    International Nuclear Information System (INIS)

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J.

    1989-01-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from [3H-nicotinamide]NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from [32P-adenylate]NAD (0.2 mol/mol of protein). Label from [3H-nicotinamide]NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with [3H-nicotinamide]NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis

  10. Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

    International Nuclear Information System (INIS)

    Pratt, B.L.; Takahashi, J.S.

    1988-01-01

    The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and [32P]ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxin partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed [32P]ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by [32P]NAD. Pertussis toxin pretreatment of pineal cells abolished [32P] radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by [32P]NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells

  11. Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.

    Science.gov (United States)

    Isbrucker, R; Daas, A; Wagner, L; Costanzo, A

    2016-01-01

    Current regulations for acellular pertussis (aP) vaccines require that they are tested for the presence of residual or reversion-derived pertussis toxin (PTx) activity using the mouse histamine sensitisation test (HIST). Although a CHO cell clustering assay can be used by manufacturers to verify if sufficient inactivation of the substance has occurred in-process, this assay cannot be used at present for the final product due to the presence of aluminium adjuvants which interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering assays which accommodate for the adjuvant effects have been proposed as alternatives to the HIST. These modified assays eliminate the adjuvant-induced cytotoxicity either through dilution of the vaccine (called the Direct Method) or by introducing a porous barrier between the adjuvant and the cells (the Indirect Method). Transferability and suitability of these methods for testing of products present on the European market were investigated during a collaborative study organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). Thirteen laboratories participated in this study which included 4 aP-containing vaccines spiked by addition of PTx. This study also assessed the transferability of a standardised CHO cell clustering assay protocol for use with non-adjuvanted PTx preparations. Results showed that the majority of laboratories were able to detect the PTx spike in all 4 vaccines at concentrations of 4 IU/mL or lower using the Indirect Method. This sensitivity is in the range of the theoretical sensitivity of the HIST. The Direct Method however did not show the expected results and would need additional development work.

  12. Pertussis toxin, an inhibitor of G(αi PCR, inhibits bile acid- and cytokine-induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Golnar Karimian

    Full Text Available Excessive hepatocyte apoptosis is a common event in acute and chronic liver diseases leading to loss of functional liver tissue. Approaches to prevent apoptosis have therefore high potential for the treatment of liver disease. G-protein coupled receptors (GPCR play crucial roles in cell fate (proliferation, cell death and act through heterotrimeric G-proteins. G(αiPCRs have been shown to regulate lipoapoptosis in hepatocytes, but their role in inflammation- or bile acid-induced apoptosis is unknown. Here, we analyzed the effect of inhibiting G(αiPCR function, using pertussis toxin (PT, on bile acid- and cytokine-induced apoptosis in hepatocytes. Primary rat hepatocytes, HepG2-rNtcp cells (human hepatocellular carcinoma cells or H-4-II-E cells (rat hepatoma cells were exposed to glycochenodeoxycholic acid (GCDCA or tumor necrosis factor-α (TNFα/actinomycin D (ActD. PT (50-200 nmol/L was added 30 minutes prior to the apoptotic stimulus. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (sytox green staining were assessed. PT significantly reduced GCDCA- and TNFα/ActD-induced apoptosis in rat hepatocytes (-60%, p<0.05 in a dose-dependent manner (with no shift to necrosis, but not in HepG2-rNtcp cells or rat H-4-II-E cells. The protective effect of pertussis toxin was independent of the activation of selected cell survival signal transduction pathways, including ERK, p38 MAPK, PI3K and PKC pathways, as specific protein kinase inhibitors did not reverse the protective effects of pertussis toxin in GCDCA-exposed hepatocytes.Pertussis toxin, an inhibitor of G(αiPCRs, protects hepatocytes, but not hepatocellular carcinoma cells, against bile acid- and cytokine-induced apoptosis and has therapeutic potential as primary hepatoprotective drug, as well as adjuvant in anti-cancer therapy.

  13. Mucosal and systemic immune responses elicited by recombinant Lactococcus lactis expressing a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis.

    Science.gov (United States)

    Torkashvand, Ali; Bahrami, Fariborz; Adib, Minoo; Ajdary, Soheila

    2018-05-05

    We constructed a food-grade expression system harboring a F1S1 fusion protein of Bordetella pertussis to be produced in Lactococcus lactis NZ3900 as a new oral vaccine model against whooping cough, caused by B. pertussis. F1S1 was composed of N-terminally truncated S1 subunit of pertussis toxin and type I immunodominant domain of filamentous hemagglutinin which are both known as protective immunogens against pertussis. The recombinant L. lactis was administered via oral or intranasal routes to BALB/c mice and the related specific systemic and mucosal immune responses were then evaluated. The results indicated significantly higher levels of specific IgA in the lung extracts and IgG in sera of mucosally-immunized mice, compared to their controls. It was revealed that higher levels of IgG2a, compared to IgG1, were produced in all mucosally-immunized mice. Moreover, immunized mice developed Th1 responses with high levels of IFN-γ production by the spleen cells. These findings provide evidence for L. lactis to be used as a suitable vehicle for expression and delivery of F1S1 fusion protein to mucosa and induction of appropriate systemic and mucosal immune responses against pertussis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. NADP+ enhances cholera and pertussis toxin-catalyzed ADP-ribosylation of membrane proteins

    International Nuclear Information System (INIS)

    Kawai, Y.; Whitsel, C.; Arinze, I.J.

    1986-01-01

    Cholera or pertussis toxin-catalyzed [ 32 P]ADP-ribosylation is frequently used to estimate the concentration of the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins which modulate the activity of adenylate cyclase. With this assay, however, the degradation of the substrate, NAD + , by endogenous enzymes such as NAD + -glycohydrolase (NADase) present in the test membranes can influence the results. In this study the authors show that both cholera and pertussis toxin-catalyzed [ 32 P]ADP-ribosylation of liver membrane proteins is markedly enhanced by NADP + . The effect is concentration dependent; with 20 μM [ 32 P]NAD + as substrate maximal enhancement is obtained at 0.5-1.0 mM NADP + . The enhancement of [ 32 P]ADP-ribosylation by NADP + was much greater than that by other known effectors such as Mg 2+ , phosphate or isoniazid. The effect of NADP + on ADP-ribosylation may occur by inhibition of the degradation of NAD + probably by acting as an alternate substrate for NADase. Among inhibitors tested (NADP + , isoniazid, imidazole, nicotinamide, L-Arg-methyl-ester and HgCl 2 ) to suppress NADase activity, NADP + was the most effective and, 10 mM, inhibited activity of the enzyme by about 90%. In membranes which contain substantial activities of NADase the inclusion of NADP + in the assay is necessary to obtain maximal ADP-ribosylation

  15. [Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

    Science.gov (United States)

    Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

    2013-01-01

    The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

  16. Amidate Prodrugs of 9-[2-(Phosphonomethoxy)Ethyl]Adenine as Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis

    Czech Academy of Sciences Publication Activity Database

    Šmídková, Markéta; Dvořáková, Alexandra; Tloušťová, Eva; Česnek, Michal; Janeba, Zlatko; Mertlíková-Kaiserová, Helena

    2014-01-01

    Roč. 58, č. 2 (2014), s. 664-671 ISSN 0066-4804 R&D Projects: GA MV VG20102015046 Grant - others:OPPC(XE) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : Bordetella pertussis * adenylate cyclase toxin * ACT * inhibitors * PMEA * amidate prodrugs Subject RIV: CC - Organic Chemistry Impact factor: 4.476, year: 2014

  17. Amidate prodrugs of 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) as inhibitors of adenylate cyclase toxin from Bordetella pertussis

    Czech Academy of Sciences Publication Activity Database

    Šmídková, Markéta; Dvořáková, Alexandra; Tloušťová, Eva; Česnek, Michal; Janeba, Zlatko; Mertlíková-Kaiserová, Helena

    2014-01-01

    Roč. 281, Suppl S1 (2014), s. 729 ISSN 1742-464X. [FEBS EMBO 2014 Conference. 30.08.2014-04.09.2014, Paris] R&D Projects: GA MŠk LO1302; GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : Bordetella pertussis * adenylyl cyclase toxin * inhibitors Subject RIV: CE - Biochemistry

  18. Nifedipine-sensitive vascular reactivity of femoral arteries in WKY: the effect of pertussis toxin pretreatment and endothelium removal

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Kuneš, Jaroslav; Zicha, Josef

    2007-01-01

    Roč. 56, č. 5 (2007), s. 663-666 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * NE-induced contraction * Ca2+ influx Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.505, year: 2007

  19. Characterization, localization and function of pertussis toxin-sensitive G proteins in the nervous systems of Aplysia and Loligo

    International Nuclear Information System (INIS)

    Vogel, S.S.

    1989-01-01

    The author has characterized pertussis toxin-sensitive G proteins in the nervous systems of the gastropod mollusc Aplysia and the cephalopod Loligo using [ 32 P]ADP-ribosylation and immunoblotting with G protein specific antisera. As in vertebrates, this class of G protein is associated with membranes and enriched in nervous tissue in Aplysia. Analysis of dissected Aplysia ganglia reveal that it is enriched in neuropil, a region containing most of the central nervous system synapses. Because both Aplysia and Loligo synaptosomes are enriched in pertussis toxin-sensitive G proteins, it is likely that they are found in synaptic terminals. Fractionation of Aplysia synaptosomes into membrane and vesicle fractions reveals that, although the majority of G protein is recovered in the plasma membrane fraction, a small proportion is recovered in the vesicle fraction. He shows that G proteins are on intracellular membranes by ADP-ribosylating extruded axoplasm with pertussis toxin. A plausible explanation for vesicular localization of G protein in axoplasm is that G proteins are transported to terminals on vesicles. He has shown, using ligature experiments with Aplysia connectives and temperature block experiments in the giant axon of Loligo, that G proteins move by anterograde fast axonal transport. Injection of pertussis toxin into the identified Aplysia neuron L10 blocks histamine-induced presynaptic inhibition of transmitter release. This suggests that pertussis toxin sensitive G proteins play a role in modulating transmitter release at synaptic terminals. In the giant synapse of Loligo, he presents preliminary data that demonstrates that the activation of G proteins in the presynaptic terminal results in decreased transmitter release

  20. A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses.

    Directory of Open Access Journals (Sweden)

    Takumi Moriuchi

    Full Text Available In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA among adults (35-44 years old, young children (4-7 years old, and older children (10-14 years old. Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children. Positive correlations were observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all age groups (rs values of 0.326-0.522, although the correlation tended to decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was significantly different when we compared the serum and purified IgG fractions among adults (p = 0.016, although this result was not observed among young and older children. Thus, it appears that some adults had non-IgG immunoglobulins to PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity index: 63.5%, similar results were observed among the children; however, the adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05. It is possible that low-avidity anti-FHA IgG is related to infection with other respiratory pathogens (e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma pneumoniae, which produces antibodies to FHA-like proteins. Our observations suggest that these adults had been infected with B. pertussis and other pathogen(s during their adulthood.

  1. Novel therapies for the treatment of pertussis disease

    Science.gov (United States)

    Scanlon, Karen M.; Skerry, Ciaran; Carbonetti, Nicholas. H.

    2015-01-01

    Whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. Previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. Early diagnosis is complicated by the non-diagnostic presentation of disease early in infection. This review focuses on previous attempts at developing novel host-directed therapies for the treatment of pertussis. In addition, two novel approaches from our group are discussed. Manipulation of the signaling pathway of sphingosine-1-phosphate, a lipid involved in many immune processes, has shown great promise, but is in its infancy. Pendrin, a host epithelial anion exchanger upregulated in the airways with B. pertussis infection, appears to drive mucus production and dysregulation of airway surface liquid pH and salinity. In addition to detailing these potential new therapeutic targets, the need for greater focus on the neonatal model of disease is highlighted. PMID:26394802

  2. Mechanisms of pertussis toxin-induced barrier dysfunction in bovine pulmonary artery endothelial cell monolayers.

    Science.gov (United States)

    Patterson, C E; Stasek, J E; Schaphorst, K L; Davis, H W; Garcia, J G

    1995-06-01

    We have previously characterized several G proteins in endothelial cells (EC) as substrates for the ADP-ribosyltransferase activity of both pertussis (PT) and cholera toxin and described the modulation of key EC physiological responses, including gap formation and barrier function, by these toxins. In this study, we investigated the mechanisms involved in PT-mediated regulation of bovine pulmonary artery endothelial cells barrier function. PT caused a dose-dependent increase in albumin transfer, dependent upon action of the holotoxin, since neither the heat-inactivated PT, the isolated oligomer, nor the protomer induced EC permeability. PT-induced gap formation and barrier dysfunction were additive to either thrombin- or thrombin receptor-activating peptide-induced permeability, suggesting that thrombin and PT utilize distinct mechanisms. PT did not result in Ca2+ mobilization or alter either basal or thrombin-induced myosin light chain phosphorylation. However, PT stimulated protein kinase C (PKC) activation, and both PKC downregulation and PKC inhibition attenuated PT-induced permeability, indicating that PKC activity is involved in PT-induced barrier dysfunction. Like thrombin-induced permeability, the PT effect was blocked by prior increases in adenosine 3',5'-cyclic monophosphate. Thus PT-catalyzed ADP-ribosylation of a G protein (possibly other than Gi) may regulate cytoskeletal protein interactions, leading to EC barrier dysfunction.

  3. Pharmacological Cyclophilin Inhibitors Prevent Intoxication of Mammalian Cells with Bordetella pertussis Toxin.

    Science.gov (United States)

    Ernst, Katharina; Eberhardt, Nina; Mittler, Ann-Katrin; Sonnabend, Michael; Anastasia, Anna; Freisinger, Simon; Schiene-Fischer, Cordelia; Malešević, Miroslav; Barth, Holger

    2018-05-01

    The Bordetella pertussis toxin (PT) is one important virulence factor causing the severe childhood disease whooping cough which still accounted for approximately 63,000 deaths worldwide in children in 2013. PT consists of PTS1, the enzymatically active (A) subunit and a non-covalently linked pentameric binding/transport (B) subunit. After endocytosis, PT takes a retrograde route to the endoplasmic reticulum (ER), where PTS1 is released into the cytosol. In the cytosol, PTS1 ADP-ribosylates inhibitory alpha subunits of trimeric GTP-binding proteins (Giα) leading to increased cAMP levels and disturbed signalling. Here, we show that the cyclophilin (Cyp) isoforms CypA and Cyp40 directly interact with PTS1 in vitro and that Cyp inhibitors cyclosporine A (CsA) and its tailored non-immunosuppressive derivative VK112 both inhibit intoxication of CHO-K1 cells with PT, as analysed in a morphology-based assay. Moreover, in cells treated with PT in the presence of CsA, the amount of ADP-ribosylated Giα was significantly reduced and less PTS1 was detected in the cytosol compared to cells treated with PT only. The results suggest that the uptake of PTS1 into the cytosol requires Cyps. Therefore, CsA/VK112 represent promising candidates for novel therapeutic strategies acting on the toxin level to prevent the severe, life-threatening symptoms caused by PT.

  4. Inactivation of Gi proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zemančíková, A.; Török, J.; Zicha, Josef; Kuneš, Jaroslav

    2008-01-01

    Roč. 57, č. 2 (2008), s. 299-302 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:VEGA(SK) 2/6150/27 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * adrenergic vasoconstriction * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

  5. Pertussis toxin-sensitive alpha-adrenergic modulation of voltage - dependent calcium channels in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S6 (2006), s. 34-34 ISSN 0263-6352. [Scientific Meeting of the International Society of Hypertension /21./. 15.10.2006-19.10.2006, Fukuoka] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * alpha adrenergic vasoconstriction * voltage-dependent calcium channels * SHR rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  6. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R. (Univ. of Utah School of Medicine, Salt Lake City (USA))

    1991-04-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

  7. Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

    International Nuclear Information System (INIS)

    Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R.

    1991-01-01

    To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function

  8. Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

    Directory of Open Access Journals (Sweden)

    Rajwahrdhan Yadav

    2010-08-01

    Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

  9. Effect of in vivo injection of cholera and pertussis toxin on glucose transport in rat skeletal muscle

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Han, X; Petersen, L N

    1997-01-01

    Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to inhibit glucose transport in perfused skeletal muscle. Twenty-five hours after an intravenous injection of CTX, basal transport was decreased approximately 30%, and insulin- and contraction-stimulated transport...... in GLUT-1 protein content was found. In contrast, GLUT-4 mRNA was unchanged, but transcripts for GLUT-1 were increased > or = 150% in all three muscles from CTX-treated rats. The findings suggest that CTX via increased cAMP impairs basal as well as insulin- and contraction-stimulated muscle glucose...

  10. Inhibition of epithelial Na+ transport by atriopeptin, protein kinase c, and pertussis toxin

    International Nuclear Information System (INIS)

    Mohrmann, M.; Cantiello, H.F.; Ausiello, D.A.

    1987-01-01

    The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na + by atrial natriuretic peptide and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK i . Using 22 Na + fluxes, they further investigated the modulation of Na + transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na + uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators of protein kinase c, inhibit Na + uptake by 93 ± 13 and 51 ± 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK i cells, inhibits 22 Na + influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na + uptake. These events may be sequentially involved in the action of atrial natriuretic peptide

  11. Long-term functional impairment of hemopoietic progenitor cells engineered to express the S1 catalytic subunit of pertussis toxin.

    Science.gov (United States)

    Bonig, Halvard; Rohmer, Laurence; Papayannopoulou, Thalia

    2005-06-01

    A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo.

  12. 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.

  13. Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress.

    Science.gov (United States)

    Suh, Hong-Won; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Im, Hyun-Ju; Hong, Jae-Seung

    2016-09-01

    In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism.

  14. Identification of a GTP-binding protein α subunit that lacks an apparent ADP-ribosylation site for pertussis toxin

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Yoshimoto, K.K.; Eversole-Cire, P.; Simon, M.I.

    1988-01-01

    Recent molecular cloning of cDNA for the α subunit of bovine transducin (a guanine nucleotide-binding regulatory protein, or G protein) has revealed the presence of two retinal-specific transducins, called T/sub r/ and T/sub c/, which are expressed in rod or cone photoreceptor cells. In a further study of G-protein diversity and signal transduction in the retina, the authors have identified a G-protein α subunit, which they refer to as G/sub z/α, by isolating a human retinal cDNA clone that cross-hybridizes at reduced stringency with bovine T/sub r/ α-subunit cDNA. The deduced amino acid sequence of G/sub z/α is 41-67% identical with those of other known G-protein α subunits. However, the 355-residue G/sub z/α lacks a consensus site for ADP-ribosylation by pertussis toxin, and its amino acid sequence varies within a number of regions that are strongly conserved among all of the other G-protein α subunits. They suggest that G/sub z/α, which appears to be highly expressed in neural tissues, represents a member of a subfamily of G proteins that mediate signal transduction in pertussis toxin-insensitive systems

  15. 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.

  16. Bisamidate Prodrugs of 2-Substituted 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA, adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis

    Czech Academy of Sciences Publication Activity Database

    Česnek, Michal; Jansa, Petr; Šmídková, Markéta; Mertlíková-Kaiserová, Helena; Dračínský, Martin; Brust, T. F.; Pávek, P.; Trejtnar, F.; Watts, V. J.; Janeba, Zlatko

    2015-01-01

    Roč. 10, č. 8 (2015), s. 1351-1364 ISSN 1860-7179 R&D Projects: GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : adenylate cyclase toxin * bisamidates * Bordetella pertussis * nucleosides * phosphonates Subject RIV: CC - Organic Chemistry Impact factor: 2.980, year: 2015

  17. Effect of small doses of ionizing radiation on motility, rosette formation, and antioxidant state of leukocytes under modification of G-proteins by cholera and pertussis toxins

    International Nuclear Information System (INIS)

    Zhirnov, V.V.; Luik, A.I.; Metelitsa, L.A.; Mogilevich, S.E.; Charochkina, L.L.

    2000-01-01

    The responses of motility and rosette formation of leukocytes to small radioactive doses (from 6 centre dot 10 -10 to 6 centre dot 10 -4 Gy) are studied. The influence of these doses on cell functions and oxidative homeostasis are investigated under the modification of transducing components of membrane signal pathways (adenylate cyclase and polyphosphoinositide cascades) with pertussis and cholera toxins

  18. 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...

  19. Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin-mediated adhesion and mechanics in alveolar epithelial cells.

    Science.gov (United States)

    Angely, Christelle; Nguyen, Ngoc-Minh; Andre Dias, Sofia; Planus, Emmanuelle; Pelle, Gabriel; Louis, Bruno; Filoche, Marcel; Chenal, Alexandre; Ladant, Daniel; Isabey, Daniel

    2017-08-01

    The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown. In this study, we use a recently proposed multiple bond force spectroscopy (MFS) with an atomic force microscope to assess the early phase of cell adhesion (maximal detachment and local rupture forces) and cell rigidity (Young's modulus) in alveolar epithelial cells (A549) for toxin exposure 95%) at CyaA concentration of 0.5 nM, but a significant effect (≈81%) at 10 nM. MFS performed on A549 for three different concentrations (0.5, 5 and 10 nM) demonstrates that CyaA toxin significantly affects both cell adhesion (detachment forces are decreased) and cell mechanics (Young's modulus is increased). CyaA toxin (at 0.5 nM) assessed at three indentation/retraction speeds (2, 5 and 10 μm/s) significantly affects global detachment forces, local rupture events and Young modulus compared with control conditions, while an enzymatically inactive variant CyaAE5 has no effect. These results reveal the loading rate dependence of the multiple bonds newly formed between the cell and integrin-specific coated probe as well as the individual bond kinetics which are only slightly affected by the patho-physiological dose of CyaA toxin. Finally, theory of multiple bond force rupture enables us to deduce the bond number N which is reduced by a factor of 2 upon CyaA exposure (N ≈ 6 versus N ≈ 12 in control conditions). MFS measurements demonstrate that adhesion and mechanical properties of A549 are deeply affected by exposure to the CyaA toxin but not to an enzymatically inactive variant. This indicates that the alteration of cell mechanics triggered by CyaA is a consequence of the increase in

  20. Channel formation in model membranes by the adenylate cyclase toxin of Bordetella pertussis: Effect if Calcium

    Czech Academy of Sciences Publication Activity Database

    Knapp, O.; Maier, E.; Polleichtner, G.; Mašín, Jiří; Šebo, Peter; Benz, R.

    2003-01-01

    Roč. 42, - (2003), s. 8077-8084 ISSN 0006-2960 R&D Projects: GA AV ČR IPP1050128 Institutional research plan: CEZ:AV0Z5020903 Keywords : bordetella pertussis * calcium Subject RIV: EE - Microbiology, Virology Impact factor: 3.922, year: 2003

  1. Update on pertussis and pertussis immunization

    Directory of Open Access Journals (Sweden)

    Jung Yun Hong

    2010-05-01

    Full Text Available Pertussis is a highly contagious respiratory tract disease caused by Bordetella pertussis infection. The clinical manifestation of this infection can be severe enough to cause death. Although pertussis has been supposed to be a vaccine-preventable disease ever since the widespread vaccination of children against pertussis was started, since the 1990s, cases of pertussis and related fatalities are on the rise, especially in countries with high vaccination coverage. In Korea, there have been no deaths due to pertussis since 1990, and the vaccination rate continues to be approximately 94%. However, the number of pertussis cases reported to the Korea Center for Disease Control and Prevention has tended to increase in the 2000s, and in 2009, there was an obvious increase in the number of pertussis cases reported. This review aims to present the latest information about the pathogenesis, diagnosis, treatment, and prevention of pertussis.

  2. IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell entry to the central nervous system

    DEFF Research Database (Denmark)

    Millward, Jason M; Caruso, Maria; Campbell, Iain L

    2007-01-01

    Inflammation of the CNS, which occurs during multiple sclerosis and experimental autoimmune encephalomyelitis, is characterized by increased levels of IFN-gamma, a cytokine not normally expressed in the CNS. To investigate the role of IFN-gamma in CNS, we used intrathecal injection of a replication......-defective adenovirus encoding murine IFN-gamma (AdIFNgamma) to IFN-gamma-deficient (GKO) mice. This method resulted in stable, long-lived expression of IFN-gamma that could be detected in cerebrospinal fluid using ELISA and Luminex bead immunoassay. IFN-gamma induced expression in the CNS of message and protein...... was predominantly localized to meningeal and ependymal cells, and was also seen in astrocytes and microglia. IFN-gamma-induced chemokine expression did not lead to inflammation. However, when pertussis toxin was given i.p. to mice infected with the IFN-gamma vector, there was a dramatic increase in the number of T...

  3. Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

    DEFF Research Database (Denmark)

    Schellenberg, Angela E; Buist, Richard; Del Bigio, Marc R

    2012-01-01

    infiltrate into the brain parenchyma following the administration of pertussis toxin (PTx). METHODS: This study uses contrast-enhanced magnetic resonance imaging (MRI) to quantify the extent of blood-brain barrier (BBB) disruption in this model pre- and post-PTx administration compared to wild type mice....... Contrast-enhanced MR images were obtained before and 1, 3, and 5 days after PTx injection in each animal. After the final imaging session fluorescent dextran tracers were administered intravenously to each mouse and brains were examined histologically for cellular infiltrates, BBB leakage and tight...... junction protein. RESULTS: BBB breakdown, defined as a disruption of both the endothelium and glia limitans, was found only in CCL2 transgenic mice following PTx administration seen on MR images as focal areas of contrast enhancement and histologically as dextrans leaking from blood vessels. No evidence...

  4. 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.

  5. Mutation in the β-hairpin of the Bordetella pertussis adenylate cyclase toxin modulates N-lobe conformation in calmodulin

    International Nuclear Information System (INIS)

    Springer, Tzvia I.; Goebel, Erich; Hariraju, Dinesh; Finley, Natosha L.

    2014-01-01

    Highlights: • Bordetella pertussis adenylate cyclase toxin modulates bi-lobal structure of CaM. • The structure and stability of the complex rely on intermolecular associations. • A novel mode of CaM-dependent activation of the adenylate cyclase toxin is proposed. - Abstract: Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD’s β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD’s β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (R h ) and reduced thermal stability in the mutant complex. Taken together

  6. Mutation in the β-hairpin of the Bordetella pertussis adenylate cyclase toxin modulates N-lobe conformation in calmodulin

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Tzvia I.; Goebel, Erich; Hariraju, Dinesh [Department of Microbiology, Miami University, Oxford, OH 45056 (United States); Finley, Natosha L., E-mail: finleynl@miamioh.edu [Department of Microbiology, Miami University, Oxford, OH 45056 (United States); Cell, Molecular, and Structural Biology Program, Miami University, Oxford, OH 45056 (United States)

    2014-10-10

    Highlights: • Bordetella pertussis adenylate cyclase toxin modulates bi-lobal structure of CaM. • The structure and stability of the complex rely on intermolecular associations. • A novel mode of CaM-dependent activation of the adenylate cyclase toxin is proposed. - Abstract: Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD’s β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD’s β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (R{sub h}) and reduced thermal stability in the mutant complex. Taken

  7. Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

    Science.gov (United States)

    Lee, Adria D; Cassiday, Pamela K; Pawloski, Lucia C; Tatti, Kathleen M; Martin, Monte D; Briere, Elizabeth C; Tondella, M Lucia; Martin, Stacey W

    2018-01-01

    The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the "gold standard," composite reference standard analysis (CRS), and latent class analysis (LCA). Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

  8. Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers

    Czech Academy of Sciences Publication Activity Database

    Hasan, Shakir; Kulkarni, N.N.; Asbjarnarson, A.; Linhartová, Irena; Osička, Radim; Šebo, Peter; Gudmundsson, H.

    2018-01-01

    Roč. 86, č. 3 (2018), č. článku e00445-17. ISSN 0019-9567 R&D Projects: GA ČR GA15-09157S; GA MZd(CZ) NV16-28126A; GA MŠk(CZ) LM2015064 Institutional support: RVO:61388971 Keywords : Bordetella pertussis * airway epithelia * CyaA Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.593, year: 2016

  9. Role of nifedipine-sensitive sympathetic vasoconstriction in maintenance of high blood pressure in spontaneously hypertensive rats: effect of Gi-protein inactivation by pertussis toxin

    Czech Academy of Sciences Publication Activity Database

    Pintérová, Mária; Karen, Petr; Kuneš, Jaroslav; Zicha, Josef

    2010-01-01

    Roč. 28, č. 5 (2010), s. 969-978 ISSN 0263-6352 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/08/0139; GA AV ČR(CZ) IAA500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : calcium channels * inhibitory G proteins * pertussis toxin Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.980, year: 2010

  10. The influence of nifedipine and pertussis toxin (PTX) on vascular responsiveness to alpha1- and alpha2-adrenergic stimulation of isolated femoral arteries

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Kuneš, Jaroslav; Paulis, Ĺudovít; Zicha, Josef

    2006-01-01

    Roč. 48, č. 4 (2006), s. 769-769 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] R&D Projects: GA MZd NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : nifedipine * pertussis toxin * vascular responsiveness * alpha1- and alpha2-adrenergic stimulation * femorel arteria Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  11. Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

    International Nuclear Information System (INIS)

    Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V.

    1991-01-01

    Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in [ 3 H]glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 μM sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis

  12. Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V. (Univ. of South Florida, Tampa (USA))

    1991-04-02

    Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in ({sup 3}H)glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 {mu}M sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis.

  13. Pertussis toxin substrate is a guanosine 5'-[beta-thio]diphosphate-, N-ethylmaleimide-, Mg2+- and temperature-sensitive GTP-binding protein.

    OpenAIRE

    Wong, S K; Martin, B R; Tolkovsky, A M

    1985-01-01

    We compared the effects of guanine nucleotides and Mg2+ on ADP-ribosylation of rat brain and liver membrane proteins catalysed by Bordetella pertussis toxin (IAP) and cholera toxin (CT). Labelling of proteins in the presence of [alpha-32P]NAD+, ATP and CT required GTP or guanosine 5'-[gamma-thio]triphosphate (GTP [S]). In contrast, labelling of one (liver) or two (brain) polypeptides by IAP was enhanced by guanosine 5'-[beta-thio]diphosphate (GDP[S]) or GTP, but was blocked by GTP[S] or guano...

  14. Effect of pertussis and cholera toxins administered supraspinally on CA3 hippocampal neuronal cell death and the blood glucose level induced by kainic acid in mice.

    Science.gov (United States)

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Sharma, Naveen; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-12-01

    The effect of cholera toxin (CTX) or pertussis toxin (PTX) administered supraspinally on hippocampal neuronal cell death in CA3 region induced by kainic acid (KA) was examined in mice. After the pretreatment with either PTX or CTX intracerebroventricularly (i.c.v.), mice were administered i.c.v. with KA. The i.c.v. treatment with KA caused a neuronal cell death in CA3 region and PTX, but not CTX, attenuated the KA-induced neuronal cell death. In addition, i.c.v. treatment with KA caused an elevation of the blood glucose level. The i.c.v. PTX pretreatment alone caused a hypoglycemia and inhibited KA-induced hyperglycemic effect. However, i.c.v. pretreatment with CTX did not affect the basal blood glucose level and KA-induced hyperglycemic effect. Moreover, KA administered i.c.v. caused an elevation of corticosterone level and reduction of the blood insulin level. Whereas, i.c.v. pretreatment with PTX further enhanced KA-induced up-regulation of corticosterone level. Furthermore, i.c.v. administration of PTX alone increased the insulin level and KA-induced hypoinsulinemic effect was reversed. In addition, PTX pretreatment reduces the KA-induced seizure activity. Our results suggest that supraspinally administered PTX, exerts neuroprotective effect against KA-induced neuronal cells death in CA3 region and neuroprotective effect of PTX is mediated by the reduction of KA-induced blood glucose level. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

    International Nuclear Information System (INIS)

    Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

    1988-01-01

    The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate [Gpp(NH)p] on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed [ 32 P]ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-α/sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-α/sub i/ or anti-α 0 antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed

  16. Bordetella pertussis commits human dendritic cells to promote a Th1/Th17 response through the activity of adenylate cyclase toxin and MAPK-pathways.

    Directory of Open Access Journals (Sweden)

    Giorgio Fedele

    Full Text Available The complex pathology of B. pertussis infection is due to multiple virulence factors having disparate effects on different cell types. We focused our investigation on the ability of B. pertussis to modulate host immunity, in particular on the role played by adenylate cyclase toxin (CyaA, an important virulence factor of B. pertussis. As a tool, we used human monocyte derived dendritic cells (MDDC, an ex vivo model useful for the evaluation of the regulatory potential of DC on T cell immune responses. The work compared MDDC functions after encounter with wild-type B. pertussis (BpWT or a mutant lacking CyaA (BpCyaA-, or the BpCyaA- strain supplemented with either the fully functional CyaA or a derivative, CyaA*, lacking adenylate cyclase activity. As a first step, MDDC maturation, cytokine production, and modulation of T helper cell polarization were evaluated. As a second step, engagement of Toll-like receptors (TLR 2 and TLR4 by B. pertussis and the signaling events connected to this were analyzed. These approaches allowed us to demonstrate that CyaA expressed by B. pertussis strongly interferes with DC functions, by reducing the expression of phenotypic markers and immunomodulatory cytokines, and blocking IL-12p70 production. B. pertussis-treated MDDC promoted a mixed Th1/Th17 polarization, and the activity of CyaA altered the Th1/Th17 balance, enhancing Th17 and limiting Th1 expansion. We also demonstrated that Th1 effectors are induced by B. pertussis-MDDC in the absence of IL-12p70 through an ERK1/2 dependent mechanism, and that p38 MAPK is essential for MDDC-driven Th17 expansion. The data suggest that CyaA mediates an escape strategy for the bacterium, since it reduces Th1 immunity and increases Th17 responses thought to be responsible, when the response is exacerbated, for enhanced lung inflammation and injury.

  17. Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor.

    Science.gov (United States)

    Versleijen, Michelle W J; van Esterik, Joantine C J; Roelofs, Hennie M J; van Emst-de Vries, Sjenet E; Willems, Peter H G M; Wanten, Geert J A

    2009-02-01

    Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)-sensitive G-protein-coupled receptor (GPCR). This finding urged us to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs. Neutrophils isolated from blood of healthy volunteers were pre-incubated with PT (0.5-1 microg/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca(2+) mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell surface adhesion (CD11b) and degranulation (CD66b) markers and oxygen radical (ROS) production. PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca(2+) concentration. LCT/MCT increased ROS production to 146% of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT. LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-coupled receptor.

  18. 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.

  19. Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells.

    Science.gov (United States)

    Hisaoka-Nakashima, Kazue; Miyano, Kanako; Matsumoto, Chie; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yokoyama, Akinobu; Uezono, Yasuhito; Morioka, Norimitsu; Nakata, Yoshihiro; Takebayashi, Minoru

    2015-05-29

    Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gα(i/o) inhibitor, but not by NF449, a Gα(s) inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gα(ο1) and Gα(i3) by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKey(TM) assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gα(i/o) activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gα(i/o) upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    International Nuclear Information System (INIS)

    Murayama, T.; Ui, M.

    1985-01-01

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45 Ca 2+ uptake into the cell monolayer, and (f) increased 86 Rb + uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca 2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca 2+ -mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca 2+ gating

  1. 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

  2. Laboratory Diagnosis of Pertussis

    Science.gov (United States)

    Schellekens, Joop F. P.; Mooi, Frits R.

    2015-01-01

    SUMMARY The introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. However, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. The resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which is responsible for the large differences in pertussis notifications between countries. Accurate laboratory diagnosis is also important for distinguishing between the several etiologic agents of pertussis-like diseases, which involve both viruses and bacteria. If pertussis is diagnosed in a timely manner, antibiotic treatment of the patient can mitigate the symptoms and prevent transmission. During an outbreak, timely diagnosis of pertussis allows prophylactic treatment of infants too young to be (fully) vaccinated, for whom pertussis is a severe, sometimes fatal disease. Finally, reliable diagnosis of pertussis is required to reveal trends in the (age-specific) disease incidence, which may point to changes in vaccine efficacy, waning immunity, and the emergence of vaccine-adapted strains. Here we review current approaches to the diagnosis of pertussis and discuss their limitations and strengths. In particular, we emphasize that the optimal diagnostic procedure depends on the stage of the disease, the age of the patient, and the vaccination status of the patient. PMID:26354823

  3. Pore-Forming and Enzymatic Activities of Bordetella pertussis Adenylate Cyclase Toxin Synergize in Promoting Lysis of Monocytes

    Czech Academy of Sciences Publication Activity Database

    Basler, Marek; Mašín, Jiří; Osička, Radim; Šebo, Peter

    2006-01-01

    Roč. 74, č. 5 (2006), s. 2207-2214 ISSN 0019-9567 R&D Projects: GA AV ČR IAA5020406; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50200510 Keywords : bordetella pertussis * cyaa * cytotoxicity Subject RIV: EE - Microbiology, Virology Impact factor: 4.004, year: 2006

  4. Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis

    Czech Academy of Sciences Publication Activity Database

    Škopová, Karolína; Tomalová, Barbora; Kanchev, Ivan; Rossmann, Pavel; Švédová, Martina; Adkins, Irena; Bíbová, Ilona; Tomala, Jakub; Mašín, Jiří; Guiso, N.; Osička, Radim; Sedláček, Radislav; Kovář, Marek; Šebo, Peter

    2017-01-01

    Roč. 85, č. 6 (2017), s. 1-22, č. článku e00937-16. ISSN 0019-9567 R&D Projects: GA MZd(CZ) NV16-28126A; GA ČR(CZ) GA13-14547S; GA ČR GA13-12885S; GA ČR GA15-09157S; GA ČR(CZ) GAP302/12/0460; GA MŠk(CZ) LM2015064; GA MŠk(CZ) LM2015040 Institutional support: RVO:61388971 ; RVO:68378050 Keywords : Bordetella pertussis * adenylate cyclase toxin-hemolysin * cAMP intoxication Subject RIV: EE - Microbiology, Virology; EE - Microbiology, Virology (UMG-J) OBOR OECD: Microbiology; Microbiology (UMG-J) Impact factor: 3.593, year: 2016

  5. Assessment of Serologic Immunity to Diphtheria-Tetanus-Pertussis After Treatment of Korean Pediatric Hematology and Oncology Patients

    Science.gov (United States)

    Kwon, Hyo Jin; Lee, Jae-Wook; Chung, Nak-Gyun; Cho, Bin; Kim, Hack-Ki

    2012-01-01

    The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination. PMID:22219618

  6. 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.

  7. Pertussis Tests

    Science.gov (United States)

    ... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... tested? Pertussis, commonly called whooping cough, is a respiratory infection caused by the bacteria Bordetella pertussis . These ...

  8. Pertussis toxin-catalyzed ADP-ribosylation of a G protein in mouse oocytes, eggs, and preimplantation embryos: Developmental changes and possible functional roles

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J.; Schultz, R.M. (Univ. of Pennsylvania, Philadelphia (USA))

    1990-06-01

    G proteins, which in many somatic cells serve as mediators of signal transduction, were identified in preimplantation mouse embryos by their capacity to undergo pertussis toxin-catalyzed ADP-ribosylation. Two pertussis toxin (PT) substrates with Mr = 38,000 and 39,000 (alpha 38 and alpha 39) are present in approximately equal amounts. Relative to the amount in freshly isolated germinal vesicle (GV)-intact oocytes, the amount of PT-catalyzed ADP-ribosylation of alpha 38-39 falls during oocyte maturation, rises between the one- and two-cell stages, falls by the eight-cell and morula stages, and increases again by the blastocyst stage. The decrease in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs during oocyte maturation, however, does not require germinal vesicle breakdown (GVBD), since inhibiting GVBD with 3-isobutyl-1-methyl xanthine (IBMX) does not prevent the decrease in the extent of PT-catalyzed ADP-ribosylation. A biologically active phorbol diester (12-O-tetradecanoyl phorbol 13-acetate), but not an inactive one (4 alpha-phorbol 12,13-didecanoate, 4 alpha-PDD), totally inhibits the increase in PT-catalyzed ADP-ribosylation of alpha 38-39 that occurs between the one- and two-cell stage; TPA inhibits cleavage, but not transcriptional activation, which occurs in the two-cell embryo. In contrast, cytochalasin D, genistein, or aphidicolin, each of which inhibits cleavage of one-cell embryos, or alpha-amanitin or H8, each of which inhibits transcriptional activation but not cleavage of one-cell embryos, have little or inhibitory effects on the increase in PT-catalyzed ADP-ribosylation of alpha 38-39. Results of immunoblotting experiments using an antibody that is highly specific for alpha il-3 reveal the presence of a cross-reactive species of Mr = 38,000 (alpha 38) in the GV-intact oocyte, metaphase II-arrested egg, and one-, two-cell embryos.

  9. MODERNIZATION OF GENEOTIPING OF STRAINS B. PERTUSSIS

    Directory of Open Access Journals (Sweden)

    G. A. Ivashinnikova

    2013-01-01

    Full Text Available The new rapid molecular genotyping method was developed for studying the structure of ptxP promoter of pertussis toxin. Method is based on PCR-RFLP analysis, which allows studying the specific restriction profiles of the B. pertussis strains and allows differentiation of the strains with the ptxP structural particularities. The developed method for genotyping of strains of B. pertussis can be hhelpful when monitoring strains of the causative agent of whooping cough in system of an epidemiological surveillance over pertussis infections, allowing observation over circulating population of B.pertussis, revealing strains of the causative agent of whooping cough with high production of pertussis toxin and to watch their distribution.

  10. 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.

  11. Seroprevalence of pertussis in the Gambia : evidence for continued circulation of bordetella pertussis despite high vaccination rates

    NARCIS (Netherlands)

    Scott, Susana; van der Sande, Marianne; Faye-Joof, Tisbeh; Mendy, Maimuna; Sanneh, Bakary; Barry Jallow, Fatou; de Melker, Hester; van der Klis, Fiona; van Gageldonk, Pieter; Mooi, Frits; Kampmann, Beate

    BACKGROUND: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa. METHODS: We evaluated antibody responses to pertussis toxin

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

    International Nuclear Information System (INIS)

    Hepler, J.R.; Harden, T.K.

    1986-01-01

    Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells

  17. 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.

  18. 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.

  19. 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.

  20. 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. 

  1. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1990-01-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

  2. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Pertussis (Whooping Cough) Outbreaks

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Pertussis Home About Pertussis Causes & Transmission Signs & Symptoms Complications ...

  9. Pertussis (Whooping Cough) Complications

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Pertussis Home About Pertussis Causes & Transmission Signs & Symptoms Complications ...

  10. Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis.

    Science.gov (United States)

    Patel, Priyesh N; Owen, Scott R; Norton, Cathey P; Emerson, Brandon T; Bronaugh, Andrea B; Ries, William R; Stephan, Scott J

    2018-05-01

    The buccinator, despite being a prominent midface muscle, has been previously overlooked as a target in the treatment of facial synkinesis with botulinum toxin. To evaluate outcomes of patients treated with botulinum toxin to the buccinator muscle in the setting of facial synkinesis. Prospective cohort study of patients who underwent treatment for facial synkinesis with botulinum toxin over multiple treatment cycles during a 1-year period was carried out in a tertiary referral center. Botulinum toxin treatment of facial musculature, including treatment cycles with and without buccinator injections. Subjective outcomes were evaluated using the Synkinesis Assessment Questionnaire (SAQ) prior to injection of botulinum toxin and 2 weeks after treatment. Outcomes of SAQ preinjection and postinjection scores were compared in patients who had at least 1 treatment cycle with and without buccinator injections. Subanalysis was performed on SAQ questions specific to buccinator function (facial tightness and lip movement). Of 84 patients who received botulinum toxin injections for facial synkinesis, 33 received injections into the buccinator muscle. Of the 33, 23 met inclusion criteria (19 [82.6%] women; mean [SD] age, 46 [10] years). These patients presented for 82 treatment visits, of which 44 (53.6%) involved buccinator injections and 38 (46.4%) were without buccinator injections. The most common etiology of facial paralysis included vestibular schwannoma (10 [43.5%] participants) and Bell Palsy (9 [39.1%] participants). All patients had improved posttreatment SAQ scores compared with prebotulinum scores regardless of buccinator treatment. Compared with treatment cycles in which the buccinator was not addressed, buccinator injections resulted in lower total postinjection SAQ scores (45.9; 95% CI, 38.8-46.8; vs 42.8; 95% CI, 41.3-50.4; P = .43) and greater differences in prebotox and postbotox injection outcomes (18; 95% CI, 16.2-21.8; vs 19; 95% CI, 14.2-21.8; P

  11. 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.

  12. Botulinum toxin and neuromodulation for overactive bladder treatment

    Directory of Open Access Journals (Sweden)

    Ramazan Yavuz Akman

    2013-03-01

    Full Text Available The overactive bladder (OAB is a symptom complex characterized by urgency with /without urge incontinence, and often associated with frequency and nocturia. First-line therapy for OAB includes behavioral therapies and anticholinergic drugs. Although a large number of patients respond to conservative or pharmacological therapy or a combination of the two, some patients are refractory and require additional options for intervention. Botulinum toxin therapy and neuromodulation are frequently used treatment options in refractory OAB patients.

  13. Immunization status of Iranian military recruits against Bordetella pertussis infection (whooping cough).

    Science.gov (United States)

    Izadi, Morteza; Afsharpaiman, Shahla; Jonaidi Jafari, Nematollah; Ranjbar, Reza; Gooya, Mohammad Mahdi; Robat Sarpooshi, Javad; Esfahani, Ali Akbar; Soheylipoor, Hamid

    2011-03-21

    Military recruits are susceptible to respiratory pathogens because of increased antibiotic resistance and the lack of an effective vaccine. The goal of the current study was to determine the immunological status of the Bordetella pertussis among conscripts in Iranian military garrisons. The study population consisted of 424 conscripts aged 18 to 21 years who enrolled for military service. They were selected using cluster stratified sampling from all military garrisons in Tehra, Iran. To determine the seroprevalence of infection, blood specimens from all recruits were collected and stored at - 20 °C until assayed. All serum samples were screened for immunoglobulin G (IgG) antibodies against Bordetella pertussis toxin (PT) and by using enzyme-linked immunosorbent assay (ELISA). The overall prevalence of B. pertussis seropositivity in military recruits was 60.6. Only 55.0% of the recruits had low awareness about the record of vaccination against B. pertussis during childhood. Among 424 studied individuals, 48 recruits (11.3%) had a positive history of whooping cough; prevalence of seropositivity in these recruits was 70.0%. Among these subjects, 61.7% were referred to a physician for treatment and only 39.6% of them were administered anti-pertussis therapy. Our study showed that military conscripts in Tehran garrisons were not serologically immune to pertussis and also confirmed the low awareness about vaccination and medical history related to pertussis infection in this high-risk subgroup of the Iranian population. Routine acellular booster vaccination, particularly before 18 years of age, is recommended.

  14. [Spasm of the near reflex. Treatment with botulinum toxin].

    Science.gov (United States)

    Merino, P; Rojas, P; Gómez de Liaño, P; Franco Iglesias, G

    2015-05-01

    A 38-year old female with diplopia and esotropia, with limitation of ocular abduction in both eyes, with full abduction after doll's head rotation also being observed. She was diagnosed with spasm of the near reflex. Treatment with injections of botulinum toxin in both medial rectus has temporally resolved the convergence spasm. Near reflex spasm is characterized as miosis, pseudomyopia, and convergent strabismus that lead to diplopia, blurred vision, headache, and variable, progressive, and intermittent esotropia. As the spasm worsens there will be limited ocular versions and ductions simulating a sixth nerve palsy. Botulinum toxin may be effective in some cases. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Botulinum toxin type A as treatment of partially accommodative esotropia.

    Science.gov (United States)

    Flores-Reyes, E M; Castillo-López, M G; Toledo-Silva, R; Vargas-Ortega, J; Murillo-Correa, C E; Aguilar-Ruiz, A

    2016-03-01

    To determine the effectiveness of a botulinum toxin type A injection in both medial rectus muscles in patients with partially accommodative esotropia. Residual deviation and stability of strabismus were evaluated at 18 months follow up. A prospective, analytical, quasi-experimental study was conducted on a cohort of 21 patients who underwent total cycloplegic refraction and with a residual deviation of at least 14 DP. A botulinum toxin type A dose of 5 IU was injected into each medial rectus muscle for a residual deviation greater than 18 DP, with a dose of 2.5 IU being used for a deviation between 14 and 18 DP. Multivariate logistic regression analyses were performed to relate residual deviation to variables recorded as potential predictors. A total of 21 patients were included, 33.3% (n=7) males and 66.6% (n=14) females. Mean visual acuity was -.28±.25 logMAR for right eye (range 0 to -1) and -.42±.31 logMAR for left eye (range 0 to -1.3). Mean angle of residual deviation before application of botulinum toxin was 40.95±8.6DP without spectacles correction, and 22.3±7.99 DP with full cycloplegic refraction. Adverse effects were ptosis in 14.2% (n=3), diplopia 23.8% (n=5), and vertical deviation in 33% (n=7). One patient had a poor outcome, therefore required surgical treatment. At one year follow up, 85.71% of patients showed good results with esotropia of 12 DP or less, dropping to 71.43% at 18 months of follow up. Botulinum toxin type A is an effective long-term treatment with a good response in 71.43% of patients. No predictors of good response were demonstrated. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Laura Julia Starost

    2016-10-01

    Full Text Available Pertussis toxin (PTx, the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

  17. Botulinum toxin in the treatment of refractory vaginismus.

    Science.gov (United States)

    Ghazizadeh, Shirin; Nikzad, Masoomeh

    2004-11-01

    To investigate the efficacy of botulinum toxin injection to treat women with moderate and severe vaginismus. Twenty-four women referred to our clinic from February 2002 to February 2004 (mean age 25 years; range 19-34 years) with third- to fourth-degree vaginismus were recruited for this study. These women had previous unsuccessful treatments. Botulinum toxin (150-400 mIU) was injected into the puborectalis muscles in 3 sites on each side of the vagina. Twenty-three patients (95.8%) had vaginal examinations 1 week postoperatively that showed little or no vaginismus, 18 (75%) achieved satisfactory intercourse after the first injection, 4 (16.7%) had mild pain, 1 was cured after a second injection, 1 patient refused vaginal examination and did not attempt to have coitus, and another had no coitus as a result of her husband's secondary impotence. The women were followed up for a mean of 12.3 months (range 2-24 months), and there were no cases of recurrence. In refractory cases of vaginismus when conventional therapies have failed, local injection of botulinum toxin can be considered. III.

  18. Calcium-dependent disorder-to-order transitions are central to the secretion and folding of the CyaA toxin of Bordetella pertussis, the causative agent of whooping cough.

    Science.gov (United States)

    O'Brien, Darragh P; Perez, Ana Cristina Sotomayor; Karst, Johanna; Cannella, Sara E; Enguéné, Véronique Yvette Ntsogo; Hessel, Audrey; Raoux-Barbot, Dorothée; Voegele, Alexis; Subrini, Orso; Davi, Marilyne; Guijarro, J Inaki; Raynal, Bertrand; Baron, Bruno; England, Patrick; Hernandez, Belen; Ghomi, Mahmoud; Hourdel, Véronique; Malosse, Christian; Chamot-Rooke, Julia; Vachette, Patrice; Durand, Dominique; Brier, Sébastien; Ladant, Daniel; Chenal, Alexandre

    2018-01-12

    The adenylate cyclase toxin (CyaA) plays an essential role in the early stages of respiratory tract colonization by Bordetella pertussis, the causative agent of whooping cough. Once secreted, CyaA invades eukaryotic cells, leading to cell death. The cell intoxication process involves a unique mechanism of translocation of the CyaA catalytic domain directly across the plasma membrane of the target cell. Herein, we review our recent results describing how calcium is involved in several steps of this intoxication process. In conditions mimicking the low calcium environment of the crowded bacterial cytosol, we show that the C-terminal, calcium-binding Repeat-in-ToXin (RTX) domain of CyaA, RD, is an extended, intrinsically disordered polypeptide chain with a significant level of local, secondary structure elements, appropriately sized for transport through the narrow channel of the secretion system. Upon secretion, the high calcium concentration in the extracellular milieu induces the refolding of RD, which likely acts as a scaffold to favor the refolding of the upstream domains of the full-length protein. Due to the presence of hydrophobic regions, CyaA is prone to aggregate into multimeric forms in vitro, in the absence of a chaotropic agent. We have recently defined the experimental conditions required for CyaA folding, comprising both calcium binding and molecular confinement. These parameters are critical for CyaA folding into a stable, monomeric and functional form. The monomeric, calcium-loaded (holo) toxin exhibits efficient liposome permeabilization and hemolytic activities in vitro, even in a fully calcium-free environment. By contrast, the toxin requires sub-millimolar calcium concentrations in solution to translocate its catalytic domain across the plasma membrane, indicating that free calcium in solution is actively involved in the CyaA toxin translocation process. Overall, this data demonstrates the remarkable adaptation of bacterial RTX toxins to the

  19. Children with pertussis inform the investigation of other pertussis cases among contacts

    Directory of Open Access Journals (Sweden)

    Rodrigues Laura C

    2007-05-01

    Full Text Available Abstract Background The number of reported pertussis has increased in the last two decades. However, many cases of pertussis may be underreported or not diagnosed. The World Health Organization estimates that pertussis causes 200.000 – 400.000 deaths each year, most deaths are in infants and in developing countries. Infants with pertussis can indicate an undetected source cases in the community. Methods At a University Hospital in Brazil individuals that had frequent contacts with a child with confirmed pertussis (the index case and had recent history of cough were enrolled into the study. Nasopharyngeal swabs were collected from every contact that had cough within the last 21 days. Cases confirmation followed the guidelines of the Center for Disease Control and Prevention – Atlanta, U.S.A. Results Pertussis diagnosis was confirmed in 51 children, (considered the index cases. Among the index cases, 72.5% (37/51 were under 6 months of age; culture for Bordetella pertussis was positive in 78.4% (40/51. Pertussis was confirmed in 39% (107/276 of the contacts of 51 index cases. Among these contacts identified as a pertussis case, 40.2% (43/107 were between 6 months and 111/2 years of age and 59.8% (64/107 were older than 111/2 years of age. Pertussis was confirmed by culture in 11.2% (12/107 of them and by epidemiologic linkage in 88.8% (95/107. Each index case allowed identifying two new cases of pertussis. Conclusion Public health authorities should consider implementing early recognition of pertussis index cases and searching for pertussis cases among the contacts. Treatment of the cases and prophylaxis of the contacts is fundamental to control outbreaks in the community.

  20. Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

    Science.gov (United States)

    Jansen, S; Jerowski, M; Ludwig, L; Fischer-Krall, E; Beutner, D; Grosheva, M

    2017-04-01

    Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm 2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A. © 2016 John Wiley & Sons Ltd.

  1. Steady-state levels of G-protein beta-subunit expression are regulated by treatment of cells with bacterial toxins

    International Nuclear Information System (INIS)

    Watkins, D.C.; Northup, J.K.; Malbon, C.C.

    1987-01-01

    Cultures of 3T3-L1 cells were incubated with either 10 ng/ml cholera toxin or 10 ng/ml pertussis toxin from 4 days prior to the initiation of differentiation and throughout the subsequent incubation. Toxin concentrations were sufficient to completely prevent the labelling of alpha-subunits with [ 32 P]NAD + and pertussis toxin and to prevent by more than 90% the labelling with [ 32 P]NAD + and cholera toxin in membranes prepared from these cells. Neither toxin prevented the differentiation to the adipocyte phenotype. Neither toxin prevented the increases in the relative amounts of G-proteins which occur upon differentiation. Both toxins dramatically decreased the amount of beta-subunits. As measured by quantitative immunoblotting with antisera specific for both the 35 kDa and 36 kDa beta-subunits, levels of beta-subunit were decreased by more than 50% of steady-state level of control cells. Thus, bacterial toxins which modifies G-protein alpha-subunits are capable of modulating the levels of beta-subunits in vivo. The basis for the regulation of G-protein subunit expression by bacterial toxins is under study

  2. The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sekiya, M.; Frohlich, E.D.; Cole, F.E. (Alton Ochsner Medical Foundation, New Orleans, LA (USA))

    1991-01-01

    In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation. In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.

  3. 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

  4. Botulinum toxin treatment for limb spasticity in childhood cerebral palsy

    Directory of Open Access Journals (Sweden)

    Vito ePavone

    2016-02-01

    Full Text Available CP is the most common cause of chronic disability in childhood occurring in 2 to 2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects and possible resistance as well as specific use in the upper and lower limbs muscles

  5. Photos of Pertussis

    Science.gov (United States)

    ... Prophylaxis Pertussis in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & ... PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file ...

  6. Pertussis Signs & Symptoms

    Science.gov (United States)

    ... Prophylaxis Pertussis in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & ... PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file ...

  7. Whooping Cough (Pertussis)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Whooping Cough (Pertussis) KidsHealth / For Parents / Whooping Cough (Pertussis) What's in this article? Signs & Symptoms Contagiousness ...

  8. Bordetella pertussis transmission

    Science.gov (United States)

    Bordetella pertussis and Bordetella bronchiseptica are Gram negative bacterial respiratory pathogens. B. pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. B. pertussis and B. bronchiseptica share mechanisms of pathogenesis and are gene...

  9. Muscle selection for treatment of cervical dystonia with botulinum toxin : A systematic review

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

    Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

  10. Muscle selection for treatment of cervical dystonia with botulinum toxin - A systematic review

    NARCIS (Netherlands)

    Nijmeijer, S. W. R.; Koelman, J. H. T. M.; Kamphuis, D. J.; Tijssen, M. A. J.

    2012-01-01

    Rationale: Cervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be

  11. Antibiotics for whooping cough (pertussis).

    Science.gov (United States)

    Altunaiji, S; Kukuruzovic, R; Curtis, N; Massie, J

    2007-07-18

    Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. Three to four review authors independently extracted data and assessed the quality of each trial. Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

  12. Pertussis-associated persistent cough in previously vaccinated children.

    Science.gov (United States)

    Principi, Nicola; Litt, David; Terranova, Leonardo; Picca, Marina; Malvaso, Concetta; Vitale, Cettina; Fry, Norman K; Esposito, Susanna

    2017-11-01

    To evaluate the role of Bordetella pertussis infection, 96 otherwise healthy 7- to 17-year-old subjects who were suffering from a cough lasting from 2 to 8 weeks were prospectively recruited. At enrolment, a nasopharyngeal swab and an oral fluid sample were obtained to search for pertussis infection by the detection of B. pertussis DNA and/or an elevated titre of anti-pertussis toxin IgG. Evidence of pertussis infection was found in 18 (18.7 %; 95 % confidence interval, 11.5-28.0) cases. In 15 cases, the disease occurred despite booster administration. In two cases, pertussis was diagnosed less than 2 years after the booster injection, whereas in the other cases it was diagnosed between 2 and 9 years after the booster dose. This study used non-invasive testing to show that pertussis is one of the most important causes of long-lasting cough in school-age subjects. Moreover, the protection offered by acellular pertussis vaccines currently wanes more rapidly than previously thought.

  13. Cyanobacteria, Toxins and Indicators: Full-Scale Monitoring & Bench-Scale Treatment Studies

    Science.gov (United States)

    Summary of: 1) Lake Erie 2014 bloom season full-scale treatment plant monitoring data for cyanobacteria and cyanobacteria toxins; 2) Follow-up work to examine the impact of pre-oxidation on suspensions of intact toxin-producing cyanobacterial cells.

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

    African Journals Online (AJOL)

    Toxin production in food as influenced by pH, thermal treatment and chemical ... carrot, spinach, pepper, tomato, onion and cooked food samples (rice, yam, beans, ... on the growth rate and toxin elaboration of E. coli, K. aerogenes, C. freundii, ...

  15. The importance of Bordetella pertussis strains which do not produce virulence factors in the epidemiology of pertussis

    Directory of Open Access Journals (Sweden)

    Maciej Polak

    2017-05-01

    Full Text Available Bordetella pertussis strains, which have lost the ability to produce antigens, such as pertactin - Prn, pertussis toxin - Ptx, filamentous haemagglutinin - FHA, fimbriae type 2 and 3 - Fim 2 and 3, tracheal colonization factor - TcfA, have recently been isolated in countries with a high vaccination coverage. The emergence of such isolates might have resulted from B. pertussis natural evolution course or adaptive mechanisms, allowing increased circulation of the pathogen in vaccinated populations. So far, the majority of described mutants were deficient in the Prn production. Prn deficient isolates were found in countries which use acellular pertussis vaccines (aP in routine immunization programmes. The increase of frequency of Prn¯ strains isolation was correlated with the period of routine vaccination with aP vaccines. In most countries, the spread of these isolates has resulted from independent mutations rather than from the expansion of a single clone. Prn¯ isolates were collected from patients showing typical clinical symptoms of pertussis found for Prn+ strains. Results of in vitro and in vivo studies have shown that Prn¯, Ptx¯ and FHA¯ isolates retain cytotoxic properties, and besides Ptx¯ isolates, were lethal in intranasally infected mice. Further explanation of the impact of antigen deficiencies on virulence and transmission of B. pertussis in the context of the continuous increase of pertussis incidence is necessary to develop a new, optimized strategy of pertussis prevention.

  16. Use of botulinum A toxin for proctalgia fugax-a case report of successful treatment.

    Science.gov (United States)

    Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

    2017-11-01

    Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments.

  17. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    Science.gov (United States)

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  18. Botulinum toxin for treatment of Frey's syndrome: report of two cases

    Directory of Open Access Journals (Sweden)

    Teive Hélio A.G.

    2003-01-01

    Full Text Available Frey's syndrome is a phenomenon of hemifacial flushing and sweating after gustatory stimulus, usually secondary to surgical trauma over the parotid gland, although other injury mechanisms may be seen. It is accepted as a result of aberrant regeneration of facial autonomic nerve fibers. Treatment evolved from ineffective medical and surgical approaches to botulinum toxin. We evaluate the effectiveness and safety of botulinum toxin in the treatment of this complication in two patients.

  19. Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

    OpenAIRE

    Grigoriou, Marios; Ioannidis, Aristeidis; Kofina, Konstantinia; Efthimiadis, Christoforos

    2017-01-01

    Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up ...

  20. [Botulinum toxin type A in headache treatment : Established and experimental indications].

    Science.gov (United States)

    Gaul, C; Holle-Lee, D; Straube, A

    2016-08-01

    In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities.

  1. Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.

    2004-01-01

    Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum

  2. Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

    Institute of Scientific and Technical Information of China (English)

    Fiorella Orellana-Peralta; Michelle Jacinto; Maria J Pons; Cludia Gomes; Carlos Bada; Isabel Reyes; Juana del Valle Mendoza; Joaquim Ruiz

    2015-01-01

    Objective:To characterize two Achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program. Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR. Results:Two Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was evaluated by disk-diffusion method and by PCR. Conclusions:Although more detailed studies are needed, the present data highlight the possibility that Achromobacter xylosoxidans, closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella, might also result in cases of whooping cough. Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.

  3. 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 ...

  4. Calf muscle volume estimates: Implications for Botulinum toxin treatment?

    DEFF Research Database (Denmark)

    Bandholm, Thomas; Sonne-Holm, Stig; Thomsen, Carsten

    2007-01-01

    An optimal botulinum toxin dose may be related to the volume of the targeted muscle. We investigated the suitability of using ultrasound and anthropometry to estimate gastrocnemius and soleus muscle volume. Gastrocnemius and soleus muscle thickness was measured in 11 cadaveric human legs, using...

  5. Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

    Science.gov (United States)

    Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

    2012-01-01

    Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream. PMID:22511955

  6. Radiotherapy for Pertussis: An Historical Assessment

    Directory of Open Access Journals (Sweden)

    Edward J. Calabrese PhD

    2017-05-01

    Full Text Available X-ray therapy was used to treat pertussis/whooping cough during a 13-year period from 1923 to 1936 in North America and Europe. Twenty studies from clinicians in the United States reported that approximately 1500 cases of pertussis were treated by X-ray therapy usually with less than 0.5 erythema dose. Young children (<3 years comprised about 70% to 80% of the cases, with the age of cases ranging from as young as 1 month to 50 years. In general, symptoms of severe coughing, vomiting episodes, and spasms were significantly relieved in about 85% of cases following up to 3 treatments, while about 15% of the cases showed nearly full relief after only 1 treatment. The X-ray therapy was also associated with a marked reduction in mortality of young (<3 years children by over 90%. Despite such reported clinical success from a wide range of experienced researchers, the use of X-rays for the treatment of pertussis in young children was controversial, principally due to concerns of exposure to the thymus and thyroid even with the availability of lead shielding. By the mid-1930s, the treatment of pertussis cases via vaccine therapy came to dominate the therapeutic arena, and the brief era of a radiotherapy option for the treatment of pertussis ended.

  7. Review of botulinum toxin type A for the prophylactic treatment of chronic daily headache

    Directory of Open Access Journals (Sweden)

    Stefan Evers

    2007-05-01

    Full Text Available Stefan EversDepartment of Neurology, University of Münster, Münster, GermanyAbstract: Botulinum toxin A is increasingly used in the treatment of idiopathic and symptomatic headache disorders. However, only few controlled trials are available and many trials can hardly be compared to each other because of different endpoints and different trial designs. In particular chronic daily headache, which is defined as an idiopathic headache occurring on more than 15 days per month for at least 3 months and a daily duration of at least 4 hours, is considered as a headache disorder with possible efficacy of botulinum toxin A. For the prophylactic treatment of chronic tension-type headache and chronic migraine, no sufficient positive evidence for a successful treatment can be obtained from randomized, double-blind, and placebo-controlled trials to date. For the treatment of chronic daily headache including medication overuse headache, there is some positive evidence for efficacy in a subgroup of patients. To date, the majority of double-blind and placebo-controlled studies do not suggest that botulinum toxin A is efficacious in the treatment of chronic idiopathic headache disorders. However, it is possible that some subgroups of patients with chronic daily headache will benefit from a long-term treatment with botulinum toxin A.Keywords: botulinum toxin A, chronic daily headache, chronic tension-type headache, chronic migraine

  8. USE OF BOTULINUM TOXIN TYPE A IN THE TREATMENT OF SPASTICITY IN CHILDREN WITH CEREBRAL PALSY

    Directory of Open Access Journals (Sweden)

    Ljiljana Lazić

    2011-06-01

    Full Text Available Cerebral palsy has an incidence of about 1-2 per 1000 live births, and in spite of the progress of neonatal medicine, it seems that the incidence will not subside in the near future. The most important characteristic of cerebral palsy is movement abnormality: spasticity, chorea, athetosis, ataxia, dystonia, as well as their different combinations. About 70% of children who suffer from cerebral palsy also suffer from some form of spasticity. Spasticity is a type of muscle hypertonicity characterized by rapid increase in resistance to passive stretching of muscles. The interest for botulinum toxin application in the treatment of spasticity has dramatically increased in the last 10 years. Botulinum toxin is the most powerful neurotoxin that is found in nature. It is produced by anaerobic bacteria – clostridium botulinum. It is produced in eight serotypes of which type A is the most commonly used. Botulinum toxin blocks neuromuscular transmission and causes irreversible weakness of the treated muscle. It has been used since 1993 in the treatment of cerebral palsy in children. The toxin effect is permanent and it results in irreversible denervation. Functional recovery is possible after 2-4 months, due to sprouting of nerve endings and the formation of new synaptic contacts. Treatment with botulinum toxin is safe. Adverse effects are rare, temporary and completely reversible. Application of botulinum toxin prevents or reduces contractures and deformities, and thus delays or avoids surgical treatment. Yet, physical therapy, which prolongs and improves the effects of botulinum toxin, remains an essential and most important form of therapy in the treatment of children with cerebral palsy.

  9. Developmental changes in the role of a pertussis toxin sensitive guanine nucleotide binding protein in the rat cardiac alpha1-adrenergic system

    International Nuclear Information System (INIS)

    Han, H.M.

    1989-01-01

    During development, the cardiac alpha 1 -adrenergic chronotropic response changes from positive in the neonate to negative in the adult. This thesis examined the possibility of a developmental change in coupling of a PT-sensitive G-protein to the alpha 1 -adrenergic receptor. Radioligand binding experiments performed with the iodinated alpha 1 -selective radioligand [ 125 I]-I-2-[β-(4-hydroxphenyl)ethylaminomethyl]tetralone ([ 125 I]-IBE 2254) demonstrated that the alpha 1 -adrenergic receptor is coupled to a G-protein in both neonatal and adult rat hearts. However, in the neonate the alpha 1 -adrenergic receptor is coupled to a PT-insensitive G-protein, whereas in the adult the alpha 1 -adrenergic receptor is coupled to both a PT-insensitive and a PT-sensitive G-protein. Consistent with the results from binding experiments, PT did not have any effect on the alpha 1 -mediated positive chronotropic response in the neonate, whereas in the adult the alpha 1 -mediated negative chronotropic response was completely converted to a positive one after PT-treatment. This thesis also examined the possibility of an alteration in coupling of the alpha 1 -adrenergic receptor to its effector under certain circumstances such as high potassium (K + ) depolarization in nerve-muscle (NM) co-cultures, a system which has been previously shown to be a convenient in vitro model to study the mature inhibitory alpha 1 -response

  10. Structure of Bordetella pertussis peptidoglycan

    International Nuclear Information System (INIS)

    Folkening, W.J.; Nogami, W.; Martin, S.A.; Rosenthal, R.S.

    1987-01-01

    Bordetella pertussis Tohama phases I and III were grown to the late-exponential phase in liquid medium containing [ 3 H]diaminopimelic acid and treated by a hot (96 0 C) sodium dodecyl sulfate extraction procedure. Washed sodium dodecyl sulfate-insoluble residue from phases I and III consisted of complexes containing protein (ca. 40%) and peptidoglycan (60 6 ). Subsequent treatment with proteinase K yielded purified peptidoglycan which contained N-acetylglucosamine, N-acetylmuramic acid, alanine, glutamic acid, and diaminopimelic acid in molar ratios of 1:1:2:1:1 and 3 H added in diaminopimelic acid was present in peptidoglycan-protein complexes and purified peptidoglycan as diaminopimelic acid exclusively and that pertussis peptidoglycan was not O acetylated, consistent with it being degraded completely by hen egg white lysozyme. Muramidase-derived disaccharide peptide monomers and peptide-cross-linked dimers and higher oligomers were isolated by molecular-sieve chromatography; from the distribution of these peptidoglycan fragments, the extent of peptide cross-linking of both phase I and III peptidoglycan was calculated to be ca. 48%. Unambiguous determination of the structure of muramidase-derived pepidoglycan fragments by fast atom bombardment-mass spectrometry and tandem mass spectrometry indicated that the pertussis peptidoglycan monomer fraction was surprisingly homogeneous, consisting of >95% N-acetylglucosaminyl-N-acetylmuramyl-alanyl-glutamyl-diaminopimelyl-alanine

  11. Efficacy of Botulinum Toxin Injections in the Treatment of Various Types of Facial Region Disorders

    Directory of Open Access Journals (Sweden)

    Arzu Çoban

    2012-12-01

    Full Text Available OBJECTIVE: Local injection of botulinum toxin is a highly effective treatment option for a wide range of movement disorders and there are reliable sources of information on its indications, effects and safety in clinical practice. In this study, we report our experience with botulinum toxin in the treatment of facial region disorders. METHODS: Patients who had been followed in the Botulinum Toxin Outpatient Clinic of the Neurology Department were retrospectively evaluated. Two preparations of botulinum toxin type A (BT-A were used. The efficacy of BT-A injections was rated according to the improvement in symptoms as follows: marked - 75-100% improvement, good - 50-74%, moderate - 25-49%, and insufficient - less than 25% symptom relief. RESULTS: One hundred eighty-two patients (73 male, 109 female with various facial region disorders were included. The efficacy rates for patients who had very good and good improvement were high in the treatment of blepharospasm, hemifacial spasm, facial synkinesis, and Meige syndrome and moderate for oromandibular dystonia and hypersalivation. Ptosis was the most common side effect. CONCLUSION: According to our results, botulinum toxin was very effective treatment for blepharospasm, Meige syndrome, hemifacial spasm and facial synkinesis, whereas it demonstrated good efficacy in oromandibular dystonia and hypersalivation

  12. Occurrence and elimination of cyanobacterial toxins in drinking water treatment plants

    International Nuclear Information System (INIS)

    Hoeger, Stefan J.; Hitzfeld, Bettina C.; Dietrich, Daniel R.

    2005-01-01

    Toxin-producing cyanobacteria (blue-green algae) are abundant in surface waters used as drinking water resources. The toxicity of one group of these toxins, the microcystins, and their presence in surface waters used for drinking water production has prompted the World Health Organization (WHO) to publish a provisional guideline value of 1.0 μg microcystin (MC)-LR/l drinking water. To verify the efficiency of two different water treatment systems with respect to reduction of cyanobacterial toxins, the concentrations of MC in water samples from surface waters and their associated water treatment plants in Switzerland and Germany were investigated. Toxin concentrations in samples from drinking water treatment plants ranged from below 1.0 μg MC-LR equiv./l to more than 8.0 μg/l in raw water and were distinctly below 1.0 μg/l after treatment. In addition, data to the worldwide occurrence of cyanobacteria in raw and final water of water works and the corresponding guidelines for cyanobacterial toxins in drinking water worldwide are summarized

  13. Preventing Pertussis (Whooping Cough)

    Science.gov (United States)

    ... causes a whooping sound. They may gag on mucus and throw up after they cough. Not every ... your baby through the placenta and your breast milk. Your baby can get protection from pertussis for ...

  14. Pertussis Frequently Asked Questions

    Science.gov (United States)

    ... driving force behind the large scale outbreaks or epidemics. However, their parents are putting them at greater risk of getting a serious pertussis infection and then possibly spreading it to other family or community members. We ...

  15. Use of botulinum A toxin for proctalgia fugax—a case report of successful treatment

    Science.gov (United States)

    Grigoriou, Marios; Ioannidis, Aristeidis; Efthimiadis, Christoforos

    2017-01-01

    Abstract Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a variety of treatments have been used, without, however, permanent results. Injection of botulinum A toxin is recently suggested as an alternative option. We present the case of a woman presenting proctalgia fugax that was untreatable through other current forms of treatment. After two administrations of botulinum A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8-month follow-up control. Botulinum A toxin injection can reduce internal anal sphincter pressure, leading to relief of symptoms, and seems a promising option with minimal morbidity in cases on proctalgia fugax that does not respond to other current treatments. PMID:29218214

  16. Spasmodic Dysphonia in Multiple Sclerosis Treatment With Botulin Toxin A: A Pilot Study.

    Science.gov (United States)

    Di Stadio, Arianna; Bernitsas, Evanthia; Restivo, Domenico Antonio; Alfonsi, Enrico; Marchese-Ragona, Rosario

    2018-04-09

    This study aims to evaluate the effect of botulin toxin A in patients with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the safety and effectiveness of this treatment in long-term observation. This is a pilot study on three relapsing-remitting MS patients with SD and their response to botulin toxin A. None of the patients reported dysphagia or other adverse events. Significant improvement was observed in terms of both voice quality and laryngostroboscopy results. The treatment effect was durable for 6-8 months. Botulin toxin A is a safe treatment that can be successfully used to treat SD in patients with MS. Larger studies are necessary to confirm our results. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  17. A pilot study to evaluate effectiveness of botulinum toxin in treatment of androgenetic alopecia in males

    Directory of Open Access Journals (Sweden)

    Sehdev Singh

    2017-01-01

    Full Text Available Introduction: Androgenetic alopecia is a common form of alopecia with multifactorial etiology. Finasteride and minoxidil are approved by the FDA for the treatment of androgenetic alopecia. Balding scalp is believed to have relative microvascular insufficiency. Blood vessels in the scalp travel through the intramuscular plane. Intramuscular injection of botulinum toxin relaxes muscles and thereby increases blood flow in balding scalp. We conducted a pilot study to evaluate the efficacy of botulinum toxin in androgenetic alopecia management. Material and Methods: The study was conducted in a tertiary care center. A total of 10 male patients with androgenetic alopecia meeting inclusion criteria of the study were included. In the scalp, 30 sites were injected with 5 U of botulinum toxin in each site. Preprocedure photograph taken and evaluation was done, which was repeated after 24 weeks. Efficacy was assessed by photography and self-assessment scoring was done by patients. Results: Of 10 patients, 8 had good to excellent response on photographic assessment. At the end of 24 weeks, 1 patient showed poor and 1 showed fair response to treatment. As per self-assessment, 7of 10 patients showed good to excellent response. Two patients had fair response and 1 patient showed poor response to treatment. Conclusion: Botulinum toxin was found to be safe and effective therapy for the management of androgenetic alopecia in this pilot study. Studies with larger sample size and randomized controlled trials are required to establish the role of botulinum toxin in the management of androgenetic alopecia.

  18. Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct genotyping of clinical specimens.

    Science.gov (United States)

    Moriuchi, Takumi; Vichit, Ork; Vutthikol, Yong; Hossain, Md Shafiqul; Samnang, Chham; Toda, Kohei; Grabovac, Varja; Hiramatsu, Yukihiro; Otsuka, Nao; Shibayama, Keigo; Kamachi, Kazunari

    2017-09-01

    This study sought to determine the genotypes of circulating Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct molecular typing of clinical specimens. DNA extracts from nasopharyngeal swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter ptxP were also investigated by DNA sequence-based typing. Forty-four DNA extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which are common in developed countries, were the predominant strain types (total 73%). The predominant profile of virulence-associated allelic genes was the combination of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire study period, whereas MT29 strains were only found in 2014-2016. The B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV) has been continuously used, resembled those observed previously in developed countries where acellular pertussis vaccines are used. Circulating B. pertussis strains in Cambodia were distinct from those in other countries using WCVs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

    DEFF Research Database (Denmark)

    Bagi, Per; Biering-Sørensen, Fin

    2004-01-01

    To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

  20. Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

    2012-01-01

    Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

  1. Actions of cholera toxin and the prevention and treatment of cholera

    Science.gov (United States)

    Holmgren, Jan

    1981-07-01

    The drastic intestinal secretion of fluid and electrolytes that is characteristic of cholera is the result of reasonably well understood cellular and biochemical actions of the toxin secreted by Vibrio cholerae. Based on this understanding it is possible to devise new techniques for the treatment and prophylaxis of cholera to complement those based on fluid replacement therapy and sanitation.

  2. Adult pertussis is unrecognized public health problem in Thailand.

    Science.gov (United States)

    Siriyakorn, Nirada; Leethong, Pornvimol; Tantawichien, Terapong; Sripakdee, Saowalak; Kerdsin, Anusak; Dejsirilert, Surang; Paitoonpong, Leilani

    2016-01-25

    Although pertussis has been considered a disease of childhood, it is also recognized as an important respiratory tract infection in adolescents and adults. However, in countries with routine vaccination against pertussis with high coverage, pertussis is not usually taken into consideration for the etiology of prolonged cough in adults. Previous studies in a variety of populations in developed countries have documented that pertussis is quite common, ranging from 2.9 to 32% of adolescents and adults with prolonged cough. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease and source of infection to the vulnerable population of infants, for whom the disease can be life threatening. We conducted a prospective study to determine the prevalence of pertussis in Thai adults with prolonged cough. Seventy-six adult patients with a cough lasting for more than 2 weeks (range, 14-180 days) were included in the present study. The data regarding medical history and physical examination were carefully analyzed. Nasopharyngeal swabs from all patients were obtained for the detection of deoxyribonucleic acid of Bordetella pertussis by the polymerase chain reaction (PCR) method. Paired serum samples were collected and tested for IgG antibody against pertussis toxin by using an ELISA method. Of 76 adult patients, 14 patients (18.4%) with the mean age of 59 (range, 28-85) years and the mean duration of cough of 34 (range, 14-120) days had laboratory evidence of acute pertussis infection. One patient was diagnosed by the PCR method, while the rest had serological diagnosis. Whooping cough is a significantly associated symptom of patients with chronic cough who had laboratory evidence of pertussis. (p < .05, odds ratio 3.75, 95% confidence interval: 1.00, 14.06) CONCLUSION: Pertussis is being increasingly recognized as a cause of prolonged, distressing cough among adults in

  3. Seroepidemiology of pertussis in a cross-sectional study of an adult general population in Denmark

    DEFF Research Database (Denmark)

    Rønn, P F; Dalby, T; Simonsen, J

    2014-01-01

    SUMMARY An increase in pertussis has been observed in several countries over the last decades, especially in adult populations. The seroprevalence of pertussis was determined in a cross-sectional study of the adult population in the Copenhagen area, Denmark, conducted between 2006 and 2008....... Specific IgG antibodies against pertussis toxin (PT) were measured in 3440 persons resulting in an age-standardized seroprevalence of 3·0% (95% confidence interval 1·9-4·7) using an IgG anti-PT cut-off of 75 IU/ml. By using antibody decay profiles from longitudinal data the estimated seroincidence was 143....../1000 person-years. In contrast, an incidence of 0·03/1000 person-years was estimated from the official data of notified cases during the same period. Of the investigated risk factors, only age and education were significantly associated with pertussis infection. This study indicates that pertussis is highly...

  4. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing

    2010-01-01

    We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children......%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  5. Reduction of Direct Health Costs Associated with Pertussis Vaccination with Acellular Vaccines in Children Aged 0-9 Years with Pertussis in Catalonia (Spain).

    Science.gov (United States)

    Plans-Rubió, Pedro; Navas, Encarna; Godoy, Pere; Carmona, Gloria; Domínguez, Angela; Jané, Mireia; Muñoz-Almagro, Carmen; Brotons, Pedro

    2018-05-14

    The aim of this study was to assess direct health costs in children with pertussis aged 0-9 years who were vaccinated, partially vaccinated, and unvaccinated during childhood, and to assess the association between pertussis costs and pertussis vaccination in Catalonia (Spain) in 2012-2013. Direct healthcare costs included pertussis treatment, pertussis detection, and preventive chemotherapy of contacts. Pertussis patients were considered vaccinated when they had received 4-5 doses, and unvaccinated or partially vaccinated when they had received 0-3 doses of vaccine. The Chi square test and the odds ratios were used to compare percentages and the t test was used to compare mean pertussis costs in different groups, considering a p case after taking into account the effect of other study variables, and €200 per case after taking into account pertussis severity. Direct healthcare costs were lower in children with pertussis aged 0-9 years vaccinated with 4-5 doses of acellular vaccines than in unvaccinated or partially vaccinated children with pertussis of the same age.

  6. Intralesional botulinum toxin-A injection for the treatment of multiple eccrine hidrocystomas.

    Science.gov (United States)

    Gheisari, Mehdi; Hamedani, Behnaz; Robati, RezaM; Mozafari, Nikoo

    2018-01-31

    Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature. Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH. Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded. In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks. Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

  7. Pertussis: Disease Villain!

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about pertussis, or whooping cough-what it is and how to protect yourself from it.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  8. Repeated treatments of drooling with botulinum toxin B in neurology

    DEFF Research Database (Denmark)

    Møller, Eigild; Daugaard, Dorthe; Holm, Ole

    2015-01-01

    OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units...

  9. Effect of ozonation on the removal of cyanobacterial toxins during drinking water treatment.

    Science.gov (United States)

    Hoeger, Stefan J; Dietrich, Daniel R; Hitzfeld, Bettina C

    2002-01-01

    Water treatment plants faced with toxic cyanobacteria have to be able to remove cyanotoxins from raw water. In this study we investigated the efficacy of ozonation coupled with various filtration steps under different cyanobacterial bloom conditions. Cyanobacteria were ozonated in a laboratory-scale batch reactor modeled on a system used by a modern waterworks, with subsequent activated carbon and sand filtration steps. The presence of cyanobacterial toxins (microcystins) was determined using the protein phosphatase inhibition assay. We found that ozone concentrations of at least 1.5 mg/L were required to provide enough oxidation potential to destroy the toxin present in 5 X 10(5 )Microcystis aeruginosa cells/mL [total organic carbon (TOC), 1.56 mg/L]. High raw water TOC was shown to reduce the efficiency of free toxin oxidation and destruction. In addition, ozonation of raw waters containing high cyanobacteria cell densities will result in cell lysis and liberation of intracellular toxins. Thus, we emphasize that only regular and simultaneous monitoring of TOC/dissolved organic carbon and cyanobacterial cell densities, in conjunction with online residual O(3) concentration determination and efficient filtration steps, can ensure the provision of safe drinking water from surface waters contaminated with toxic cyanobacterial blooms. PMID:12417484

  10. Pertussis outbreak in Polish shooters with adverse event analysis

    Directory of Open Access Journals (Sweden)

    Monika Skrzypiec-Spring

    2017-04-01

    Full Text Available In addition to different injuries, infections are the most common reason for giving up training altogether or reducing its volume and intensity, as well as a lack of opportunities to participate in sports competitions. Nowadays, a slow but constant re‑emergence of pertussis, especially among teenagers and young adults, including athletes, can be observed. This paper describes an outbreak of pertussis among professional Polish shooters, focusing on the transmission of Bordetella pertussis infection between members of the national team, its influence on performance capacity and adverse event analysis. From 9 June, 2015 to 31 July, 2015, a total of 4 confirmed and suspected cases of pertussis were reported among members of the Polish Sport Shooting National Team, their relatives and acquaintances. Pertussis significantly decreased exercise performance of the first athlete, a 35-year-old woman, interrupted her training, and finally resulted in failure to win a medal or quota place. Pertussis also significantly decreased performance of the second athlete, a 25-year-old shooter. The other cases emerged in their families. Whooping cough is a real threat to athletes and should be prevented. Preventive measures include appropriate immunization, constant medical supervision, as well as early isolation, diagnostic tests and treatment of all infected sport team members. Regular administration of booster doses of the acellular pertussis vaccine (Tdpa every 5 years seems reasonable.

  11. 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; ...

  12. Differences in Purinergic Amplification of Osmotic Cell Lysis by the Pore-Forming RTX Toxins Bordetella pertussis CyaA and Actinobacillus pleuropneumoniae ApxIA: the Role of Pore Size

    Czech Academy of Sciences Publication Activity Database

    Mašín, Jiří; Fišer, Radovan; Linhartová, Irena; Osička, Radim; Bumba, Ladislav; Hewlett, E. L.; Benz, R.; Šebo, Peter

    2013-01-01

    Roč. 81, č. 12 (2013), s. 4571-4582 ISSN 0019-9567 R&D Projects: GA ČR GAP302/12/0460; GA ČR(CZ) GAP302/11/0580; GA ČR(CZ) GAP207/11/0717; GA AV ČR IAA500200914; GA ČR GA13-14547S Institutional support: RVO:61388971 Keywords : Bordetella pertussis * Actinobacillus pleuropneumoniae * E- coli Subject RIV: EE - Microbiology, Virology Impact factor: 4.156, year: 2013

  13. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... and Extremus posters videos mono pertussis Silence the Sounds of Pertussis Acalla los Sonidos de la Tos ... know has hbv/hcv standard precautions Silence the Sounds of Pertussis spokespeople who we are Your Choice! ...

  14. [Treatment of proctalgia fugax with botulinum toxin: results in 5 patients].

    Science.gov (United States)

    Sánchez Romero, A M; Arroyo Sebastián, A; Pérez Vicente, F A; Serrano Paz, P; Candela Polo, F; Calpena Rico, R

    2006-03-01

    Proctalgia fugax can be defined as transitory but recurrent anal pain. Although its etiology remains unknown, an internal anal sphincter spasm seems to be the most likely, so that the different treatments focus on reducing the pressure of the internal anal sphincter. This study is aimed at evaluating the effectiveness of botulinum A toxin in the treatment of proctalgia fugax. Prospective clinical trial of patients with proctalgia fugax treated with botulinum A toxin at the Outpatient Clinic attached to the Coloproctogy Unit, University Hospital of Elche, from January 1999 to January 2002. The patients included in the study underwent rectal digital examination, anuscopy, rectoscopy, anal manometry and ultrasonography, barium enema and pelvic CT scan to rule out any organic cause for anal pain. The treatment consisted of 25 IU of botulinum A toxin, with a supplementary dose of 50 IU in those patients with persistence of anal pain episodes within the next two months. The patients were reviewed on the first week, second month, sixth month and first and second year. Anal pain was measured by the patients, using a linear analogue scale from 0 to 10, and continence was assessed at every visit using the Cleveland Continence Grading Scale. Five patients were recluted for the study, with a predominance of females (4 vs. 1). Mean age was 45 years. Length of symptoms prior to the treatment was 13 months (range: 6-18 months). Only one female patient required a second dose of botulinum A toxin to handle the anal pain. All the patients healed and remained free of pain up to finishing the follow-up. There were no local complications. Anal manometry showed an increased MRP (mean resting pressure) in comparison to a control group of patients (114 mmHg vs. 66 mmHg; p proctalgia fugax.

  15. Botulinum toxin as treatment for focal dystonia : a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  16. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value

    NARCIS (Netherlands)

    Zoons, E.; Dijkgraaf, M. G. W.; Dijk, J. M.; van Schaik, I. N.; Tijssen, M. A.

    2012-01-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the

  17. Treatment of hemifacial spasm with botulinum A toxin. Results and rationale.

    Science.gov (United States)

    Gonnering, R S

    1986-01-01

    Hemifacial spasm is characterized by unilateral, periodic, tonic contractions of facial muscles, thought to be caused by mechanical compression at the root-exit zone of the facial nerve. Electrophysiologic abnormalities such as ectopic excitation and synkinesis are typical. Although posterior fossa microsurgical nerve decompression is successful in bringing about relief of the spasm in most cases, it carries a risk to hearing. As an alternative treatment, 15 patients with hemifacial spasm were given a total of 41 sets of injections with botulinum A toxin, with a mean follow-up of 14.3 +/- 1.1 months. Relief of symptoms lasted a mean of 108.3 +/- 4.2 days. Mild transient lagophthalmos and ptosis were the only complications. Although the exact mechanism of its action and beneficial effect is speculative at this time, botulinum A toxin appears to offer an effective, safe alternative to more radical intracranial surgery for patients with hemifacial spasm.

  18. The seroepidemiology of pertussis in Australia during an epidemic period.

    Science.gov (United States)

    Cagney, M; MacIntyre, C R; McIntyre, P; Puech, M; Giammanco, A

    2006-12-01

    Studying the epidemiology of pertussis and impact of differing vaccine schedules is difficult because of differing methods of case ascertainment. The advent of internationally standardized serological diagnosis for recent infection has allowed comparison of age-specific pertussis infection among European countries and was applied in Australia at the time of a major national epidemic. In 1997 and 1998, a nationally representative serum bank using residual sera from diagnostic laboratories was established. Measurement of pertussis toxin (PT) IgG level was conducted by a reference laboratory using an enzyme-linked immunosorbent assay standardized for a number of European countries. A titre of 125 EU/ml was interpreted as indicative of recent pertussis infection. The serological data were correlated with age, gender, region and disease epidemiology in Australia. The highest prevalence of recent pertussis infection was in the 5-9 years age group, and the lowest in 1-4 and 25-64 years age groups. In the 5-14 years age group, 29.7% (5-9 years) and 14.6% (10-14 years) of the sample had serological evidence of recent infection, correlating with the pattern of epidemic notifications. The 15- to 24-year-olds had similar high titres but the same notification rate as 25- to 44-year-olds, suggesting ascertainment bias may result in under-notification in the former age group. The prevalence of high titres observed was up to 20-fold higher than some European countries during a similar time period. Although vaccination has reduced the transmission of pertussis in the youngest and most vulnerable age group, pertussis is still endemic in Australia, particularly in older children and the elderly. The Australian vaccination schedule has been changed in an attempt to address this problem, by spacing doses more widely, with the fifth dose at 15-17 years of age. Seroepidemiology for pertussis offers the potential to compare patterns of pertussis between countries and examine the impact of

  19. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.

    Science.gov (United States)

    Dorji, Dorji; Mooi, Frits; Yantorno, Osvaldo; Deora, Rajendar; Graham, Ross M; Mukkur, Trilochan K

    2018-02-01

    Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis. Despite induction of both antibody and cell-mediated immune (CMI) responses by aP and wP vaccines, there has been resurgence of pertussis in many countries in recent years. Possible reasons hypothesised for resurgence have ranged from incompliance with the recommended vaccination programmes with the currently used aP vaccine to infection with a resurged clinical isolates characterised by mutations in the virulence factors, resulting in antigenic divergence with vaccine strain, and increased production of pertussis toxin, resulting in dampening of immune responses. While use of these vaccines provide varying degrees of protection against whooping cough, protection against infection and transmission appears to be less effective, warranting continuation of efforts in the development of an improved pertussis vaccine formulations capable of achieving this objective. Major approaches currently under evaluation for the development of an improved pertussis vaccine include identification of novel biofilm-associated antigens for incorporation in current aP vaccine formulations, development of live attenuated vaccines and discovery of novel non-toxic adjuvants capable of inducing both antibody and CMI. In this review, the potential roles of different accredited virulence factors, including novel biofilm-associated antigens, of B. pertussis in the evolution, formulation and delivery of improved pertussis vaccines, with potential to block the transmission of whooping cough in the community, are discussed.

  20. Antidotal Efficacy of a New Combination in Treatment of Subacute T-2 Toxin Poisoning in Rats

    International Nuclear Information System (INIS)

    Jacevic, V. M.; Bocarov-Stancic, A. S.; Resanovic, R. D.; Djordjevic, S. B.; Bokonjic, D. R.

    2007-01-01

    Trichothecene mycotoxin, T-2 toxin is a natural metabolite of Fusarium fungi. T-2 toxin possesses several properties (significant persistence in the environment, cheap manufacture, difficult detection and absence of a specific antidote) that make it a very dangerous potential chemical warfare agent. In our previous experiments, nonsteroidal anti-inflammatory drug (NSAID) nimesulide (NIM), as a selective COX-2 inhibitor, and zeolite absorbent (Min-a-zel Plus, MINplus) administered separately showed a good protective effects against general toxicity induced by T-2 toxin (T2). The aim of this study was to evaluate the antidotal potential of the combination of these two antidotes. T2 was given in a dose of 0.15 mg/kg sc (0.1 LD50), 5 times per week, 4 weeks to adult Wistar rats. Protected animals were given NIM (20 mg/kg im) or/and MINplus (40 mg/kg po) each time immediately after T2. Mortality, general condition, body weight gain, food and water consumption and gut alterations of the animals were registered on a daily basis during 4 weeks. Treatment with NIM or/and MINplus significantly reduced mortality of the rats treated only with T2. Body weight gain, food and water consumption were significantly decreased in T2-treated animals compared to control ones (p < 0.001), what was not the case in the protected rats. In the groups treated with NIM and MINplus gut alterations were significantly less severe than those observed in animals receiving T2 alone (p less than 0.001). These results imply that combined treatment with nimesulide and zeolite absorbent affords a significant protection against subacute T-2 toxin poisoning in rats.(author)

  1. Botulinum toxin efficacy in the treatment of patients with spasmodic dysphonia

    Directory of Open Access Journals (Sweden)

    Svetel Marina

    2007-01-01

    Full Text Available Background/Aim. Spasmodic dysphonia (DS is a disabling speech disturbance appearing as the consequence of dystonic vocal folds contraction. Its intermittent appearance in the laryngeal muscles causes vocal function discontinuation. The quality of life of these patients is significantly disturbed. Surgical and a medical therapy appear to be inadequate and unsuccessful ones of no steady improvement. It is the botulinum toxin therapy that proved to be highly efficacious one, with the established improvement in 80−100% of patients. The aim of our study was to evaluate the efficacy of botulinum toxin therapy in patients with SD and to show our preliminary results. Methods. The study included 10 patients with adductor spasmodic dysphonia. After diagnostic procedures, botulinum toxin was applied either in one or both vocal folds, in doses of 12−16 units each. In our study we applied indirect technique originally developed by Hočevar and Pirtošek. Perceptive voice and speech analysis was performed prior to and after the instillation of botuline toxin as per structured Scale of pathological characteristics of voice and speech appearing in the spasmodic dysphonia. Results. The majority of our patients experienced both subjective improvement and the improvement in the terms of the quality of life, Voice Henolicap Index − (VHI that was rated as rather significant one (t = 3.562; p = 0.006. Conclusion. Regardless unquestionable improvement of definite phonation, further function restitution requires individual vocal therapy and psychotherapy. Vocal therapy includes structural vocal techniques which reduce degree of vocal tension and rapid changes in the power and the height of voice. Further investigations are necessary for the scope of the definition of a standardized therapeutically procedure for spasmodic dysphonia treatment which comprises multidisciplinary approach in diagnosis, therapy and treatment efficacy evaluation.

  2. Monospecific antibody against Bordetella pertussis Adenylate Cyclase protects from Pertussis

    Directory of Open Access Journals (Sweden)

    Yasmeen Faiz Kazi

    2012-06-01

    Full Text Available Objectives: Acellular pertussis vaccines has been largely accepted world-wide however, there are reports about limitedantibody response against these vaccines suggesting that multiple antigens should be included in acellular vaccinesto attain full protection. The aim of present study was to evaluate the role of Bordetella pertussis adenylate cyclase as aprotective antigen.Materials and methods: Highly mono-specific antibody against adenylate cyclase (AC was raised in rabbits usingnitrocellulose bound adenylate cyclase and the specificity was assessed by immuoblotting. B.pertussis 18-323, wasincubated with the mono-specific serum and without serum as a control. Mice were challenged intra-nasally and pathophysiolgicalresponses were recorded.Results: The production of B.pertussis adenylate cyclase monospecific antibody that successfully recognized on immunoblotand gave protection against fatality (p< 0.01 and lung consolidation (p <0.01. Mouse weight gain showedsignificant difference (p< 0.05.Conclusion: These preliminary results highlight the role of the B.pertussis adenylate cyclase as a potential pertussisvaccine candidate. B.pertussis AC exhibited significant protection against pertussis in murine model. J Microbiol InfectDis 2012; 2(2: 36-43Key words: Pertussis; monospecific; antibody; passive-protection

  3. Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care.

    Science.gov (United States)

    Teepe, Jolien; Broekhuizen, Berna D L; Ieven, Margareta; Loens, Katherine; Huygen, Kris; Kretzschmar, Mirjam; de Melker, Hester; Butler, Chris C; Little, Paul; Stuart, Beth; Coenen, Samuel; Goossens, Herman; Verheij, Theo J M

    2015-10-01

    Most cases of adult pertussis probably remain undiagnosed. To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Prospective observational study between 2007 and 2010 in primary care in 12 European countries. Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. © British Journal of General Practice 2015.

  4. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2016-03-01

    Full Text Available The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

  5. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    Science.gov (United States)

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Methods. Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable. PMID:25383369

  6. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    Directory of Open Access Journals (Sweden)

    Jae Wook Kim

    2014-01-01

    Full Text Available Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group. Methods. Thirty patients with adductor spasmodic dysphonia (ADSD, who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P>0.05. There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  7. Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin injection in adductor spasmodic dysphonia patients: a prospective comparative study.

    Science.gov (United States)

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  8. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

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    Valérie Bouchez

    2015-09-01

    Full Text Available Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN, were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA or pertussis toxin (PT deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells.

  9. Long-term outcomes of Botulinum toxin in the treatment of chronic anal fissure: 5 years of follow-up.

    Science.gov (United States)

    Barbeiro, Sandra; Atalaia-Martins, Catarina; Marcos, Pedro; Gonçalves, Cláudia; Canhoto, Manuela; Arroja, Bruno; Silva, Filipe; Cotrim, Isabel; Eliseu, Liliana; Santos, Antonieta; Vasconcelos, Helena

    2017-03-01

    Chronic anal fissure is a frequent and disabling disease, often affecting young adults. Botulinum toxin and lateral internal sphincterotomy are the main therapeutic options for refractory cases. Botulinum toxin is minimally invasive and safer compared with surgery, which carries a difficult post-operative recovery and fecal incontinence risk. The long-term efficacy of Botulinum toxin is not well known. The aim of this study was to evaluate the long-term efficacy and safety of Botulinum toxin in the treatment of chronic anal fissure. This was a retrospective study at a single center, including patients treated with Botulinum toxin from 2005 to 2010, followed over at least a period of 5 years. All patients were treated with injection of 25U of Botulinum toxin in the intersphincteric groove. The response was registered as complete, partial, refractory and relapse. Botulinum toxin was administered to 126 patients, 69.8% ( n  = 88) were followed over a period of 5 years. After 3 months, 46.6% ( n  = 41) had complete response, 23.9% ( n  = 21) had partial response and 29.5% ( n  = 26) were refractory. Relapse was observed in 1.2% ( n  = 1) at 6 months, 11.4% ( n  = 10) at 1 year, 2.3% ( n  = 2) at 3 years; no relapse at 5 years. The overall success rate was 64.8% at 5 years of follow-up. Botulinum toxin was well tolerated by all patients and there were no complications. The use of Botulinum toxin to treat patients with chronic anal fissure was safe and effective in long-term follow-up.

  10. The utility of EMG interference pattern analysis in botulinum toxin treatment of torticollis: A randomised, controlled and blinded study

    DEFF Research Database (Denmark)

    Werdelin, L; Dalager, T; Fuglsang-Frederiksen, Anders

    2011-01-01

    OBJECTIVE: The significance of electromyography (EMG) guidance in botulinum toxin (BT) treatment has been much debated. The aim of this study was to evaluate if EMG guidance in the treatment of torticollis in BT-naive patients had a better outcome than treatment after clinical evaluation alone...

  11. Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough.

    Science.gov (United States)

    Kapil, Parul; Papin, James F; Wolf, Roman F; Zimmerman, Lindsey I; Wagner, Leslie D; Merkel, Tod J

    2018-03-28

    Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

  12. An overview of the cosmetic treatment of facial muscles with a new botulinum toxin.

    Science.gov (United States)

    Wiest, Luitgard G

    2009-01-01

    Botulinum toxin (BTX) is used nowadays in a much more differentiated way with a much more individualized approach to the cosmetic treatment of patients. To the well known areas of the upper face new indications in the mid and lower face have been added. Microinjection techniques are increasingly used besides the classic intramuscular injection technique. BTX injections of the mid and lower face require small and smallest dosages. The perioral muscles act in concert to achieve the extraordinarily complex movements that control facial expressions, eating, and speech. As the mouth has horizontal as well as vertical movements, paralysis of these perioral muscles has a greater effect on facial function and appearance than does paralysis of muscles of the upper face, which move primarily in vertical direction. It is essential that BTX injections should achieve the desired cosmetic result with the minimum dose without any functional discomfort. In this paper the three-year clinical experience with average dosages for an optimal outcome in the treatment of facial muscles with a newly developed botulinum toxin type A (Xeomin) free from complexing proteins is presented.

  13. Circadian Dysfunction in Response to in Vivo Treatment with the Mitochondrial Toxin 3-Nitropropionic Acid

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    Takashi Kudo

    2013-12-01

    Full Text Available Sleep disorders are common in neurodegenerative diseases including Huntington's disease (HD and develop early in the disease process. Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases. In the present study, we evaluated the circadian system of mice after inhibiting mitochondrial complex II of the respiratory chain with the toxin 3-nitropropionic acid (3-NP. We found that a subset of mice treated with low doses of 3-NP exhibited severe circadian deficit in behavior. The temporal patterning of sleep behavior is also disrupted in some mice with evidence of difficulty in the initiation of sleep behavior. Using the open field test during the normal sleep phase, we found that the 3-NP-treated mice were hyperactive. The molecular clockwork responsible for the generation of circadian rhythms as measured by PER2::LUCIFERASE was disrupted in a subset of mice. Within the SCN, the 3-NP treatment resulted in a reduction in daytime firing rate in the subset of mice which had a behavioral deficit. Anatomically, we confirmed that all of the treated mice showed evidence for cell loss within the striatum but we did not see evidence for gross SCN pathology. Together, the data demonstrates that chronic treatment with low doses of the mitochondrial toxin 3-NP produced circadian deficits in a subset of treated mice. This work does raise the possibility that the neural damage produced by mitochondrial dysfunction can contribute to the sleep/circadian dysfunction seen so commonly in neurodegenerative diseases.

  14. Probing the genome-scale metabolic landscape of Bordetella pertussis, the causative agent of whooping cough.

    Science.gov (United States)

    Branco Dos Santos, Filipe; Olivier, Brett G; Boele, Joost; Smessaert, Vincent; De Rop, Philippe; Krumpochova, Petra; Klau, Gunnar W; Giera, Martin; Dehottay, Philippe; Teusink, Bas; Goffin, Philippe

    2017-08-25

    Whooping cough is a highly-contagious respiratory disease caused by Bordetella pertussi s. Despite vaccination, its incidence has been rising alarmingly, and yet, the physiology of B. pertussis remains poorly understood. We combined genome-scale metabolic reconstruction, a novel optimization algorithm and experimental data to probe the full metabolic potential of this pathogen, using strain Tohama I as a reference. Experimental validation showed that B. pertussis secretes a significant proportion of nitrogen as arginine and purine nucleosides, which may contribute to modulation of the host response. We also found that B. pertussis can be unexpectedly versatile, being able to metabolize many compounds while displaying minimal nutrient requirements. It can grow without cysteine - using inorganic sulfur sources such as thiosulfate - and it can grow on organic acids such as citrate or lactate as sole carbon sources, providing in vivo demonstration that its TCA cycle is functional. Although the metabolic reconstruction of eight additional strains indicates that the structural genes underlying this metabolic flexibility are widespread, experimental validation suggests a role of strain-specific regulatory mechanisms in shaping metabolic capabilities. Among five alternative strains tested, three were shown to grow on substrate combinations requiring a functional TCA cycle, but only one could use thiosulfate. Finally, the metabolic model was used to rationally design growth media with over two-fold improvements in pertussis toxin production. This study thus provides novel insights into B. pertussis physiology, and highlights the potential, but also limitations of models solely based on metabolic gene content. IMPORTANCE The metabolic capabilities of Bordetella pertussis - the causative agent of whooping cough - were investigated from a systems-level perspective. We constructed a comprehensive genome-scale metabolic model for B. pertussis , and challenged its predictions

  15. Comparison of Pneumatic Dilation with Pneumatic Dilation Plus Botulinum Toxin for Treatment of Achalasia

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    Alireza Bakhshipour

    2010-03-01

    Full Text Available Among the therapeutic options for achalasia are pneumatic dilatation (PD, an appropriate long-term therapy, and botulinum toxin injection (BT that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty- four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3month of late PD were randomized to receive pneumatic dilation (n=18 or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16, PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score ≥ 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7, 87.5% vs. 61.1% (P = 0.59 and 87.5% vs. 55.5% (P = 0.53 at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002 and 50.77% in the PD group (P < 0.01 at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  16. Botulinum toxin

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    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.

  17. A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis

    Science.gov (United States)

    Kupsch, Andreas; Müngersdorf, Martina; Paus, Sebastian; Stenner, Andrea; Jost, Wolfgang

    2011-01-01

    Objectives Few studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis. Design Patients (aged ≥18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle. Results In this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by −4.01, −3.76 and −4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%). Conclusions Dysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment. Clinical trials information (NCT00447772; clinicaltrials.gov) PMID:22021883

  18. Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study.

    Science.gov (United States)

    Wang, Kay; Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony

    2014-06-24

    To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Prospective cohort study (November 2010 to December 2012). General practices in Thames Valley, UK. 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks' duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the need for an adolescent pertussis booster vaccination in the United Kingdom. UK

  19. Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of Inflammatory Diseases of the Mucosa

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    Joshua M. Royal

    2017-11-01

    Full Text Available Cholera toxin B subunit (CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB’s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.

  20. Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: Efficacy and possible mechanisms

    DEFF Research Database (Denmark)

    Møller, Eigild; Karlsborg, Merete; Jensen, Allan Bardow

    2011-01-01

    Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A).......Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A)....

  1. Development of improved pertussis vaccine.

    Science.gov (United States)

    Rumbo, Martin; Hozbor, Daniela

    2014-01-01

    Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized.

  2. Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

    2016-09-01

    Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

  3. Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

    Science.gov (United States)

    Al-Wayli, Hessa

    2017-01-01

    Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin. PMID:28149474

  4. Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin.

    Science.gov (United States)

    Esposito, Marcello; Dubbioso, R; Apisa, P; Allocca, R; Santoro, L; Cesari, U

    2015-09-01

    Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.

  5. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

    Science.gov (United States)

    Hendrikx, Lotte H; Oztürk, Kemal; de Rond, Lia G H; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-02-04

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore protection against pertussis may depend largely on long-term B- and T-cell immunities. We investigated long-term pertussis-specific memory B-cell responses in children who were primed at infant age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to the same antigens were measured by a fluorescent bead-based multiplex immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were found. At the same time, however pertussis protein-specific memory B-cells could be detected and their number increased with age. The number of tetanus-specific memory B-cells was similar in all age groups, whereas IgG-tetanus levels were high 2 years after tetanus booster compared to pre- and 5 years post-booster levels. This study shows the presence of long-term pertussis protein-specific memory B-cells in children despite waning antibody levels after vaccination, which suggests that memory B-cells in addition to antibodies may contribute to protection against pertussis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Bordetella pertussis diagnosis in children under five years of age in the Regional Hospital of Cajamarca, Northern Peru.

    Science.gov (United States)

    Del Valle-Mendoza, Juana; Casabona-Oré, Veronica; Petrozzi-Helasvuo, Veronica; Cornejo-Tapia, Angela; Weilg, Pablo; Pons, Maria J; Cieza-Mora, Erico; Bazán-Mayra, Jorge; Cornejo-Pacherres, Hernan; Ruiz, Joaquin

    2015-11-30

    Bordetella pertussis is an important human pathogen that causes whooping cough (pertussis), an endemic illness responsible of significant morbidity and mortality, especially in infants and children. Worldwide, there are an estimated of 16 million cases of pertussis, resulting in about 195,000 child deaths per year. In Peru, pertussis is a major health problem that has been on the increase despite immunization efforts. The objective of this study was to determine the prevalence of B. pertussis among children under five years of age suspected to have whopping cough in Cajamarca, Peru. Children diagnosed with whooping cough admitted to the Hospital Regional de Cajamarca from August 2010 to July 2013 were included. Nasopharyngeal samples were obtained for B. pertussis culture and polymerase chain reaction (PCR) detection. In 133 children, the pertussis toxin and IS481 gene were detected in 38.35% (51/133) of the cases by PCR, while only 9.02% (12/133) of the Bordetella cultures were positive. The most frequent symptoms in patients with positive B. pertussis were paroxysm of coughing 68.63% (35/51), cyanosis 56.86% (29/51), respiratory distress 43.14% (22/51), and fever 39.22% (20/51). Pneumonia and acute bronchial obstructive syndrome were present in 17.65% (9/51) and 13.72% (7/51) of the cases, respectively. B. pertussis is responsible for an important proportion of whooping cough in hospitalized children in Cajamarca. Epidemiologic surveillance programs for B. pertussis are essential in Peru, especially in children who could most benefit from the vaccine.

  7. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Pertussis (Whooping Cough) One family's struggles with pertussis ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  8. 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 ( ...

  9. Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

    Science.gov (United States)

    Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M

    2015-05-01

    To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended towards statistical significance (p bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    S. Deffontaines-Rufin

    2011-10-01

    Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

  11. Clinical presentation of infants hospitalised with pertussis

    African Journals Online (AJOL)

    [7] In SA, whole-cell pertussis vaccine (administered as a trivalent vaccine to include tetanus and diphtheria) was replaced by acellular pertussis vaccine in 2009. The pentavalent vaccine (diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and haemophilus influenza type b (DTaP-. IPV/Hib) was also introduced ...

  12. Botulinum toxin type A chemodenervation treatment in spastic forms of cerebral palsy

    Directory of Open Access Journals (Sweden)

    A. L. Kurenkov

    2013-01-01

    Full Text Available Cerebral palsy (CP is one of the most serious outcomes of the perinatal lesion of central nervous system and the most common reason for neurological disability in children. Being the key cause of pathological dynamic stereotypes that frequently result in pathological posture and contractures, spasticity is critically important for CP. The use of botulinum toxin type A (BTA in complex treatment 2-6 years old CP patients allows significantly to improve motor abilities, help to change the surgical procedure, delay or even avoid some types of surgery. For elder children the use of BTA allows to improve local motor impairment. The treatment of spasticity in CP with BTA is safe (evidence level A and highly effective (evidence level A. It leads to the positive change of pathological dynamic stereotype, significantly improves gait, decreases muscle tone with Ashworth and Tardeu scales and rises the gross motor function score. Our own experience of onabotulinumtoxinA treatment as a part of complex therapy in 68 patients with spastic forms of CP demonstrates the significant improvement of motor function, most noticeable in younger patients(early pre-school age with GMFS I-III.

  13. Botulinum toxin in the treatment of orofacial tardive dyskinesia : A single blind study

    NARCIS (Netherlands)

    Slotema, Christina W.; van Harten, Peter N.; Bruggeman, Richard; Hoek, Hans W.

    2008-01-01

    Objective: Orofacial tardive dyskinesia (OTD) is difficult to treat and Botulinium Toxin A (BTA) may be an option. Methods: In a single blind (raters were blind) study (N= 12, duration 33 weeks) OTD was treated with Botulinum Toxin A in three consecutive sessions with increasing dosages. The

  14. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing

    2010-01-01

    We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children...... had received three doses of vaccine. PT IgA responders did not have significantly longer coughing episodes than PT IgA non-responders. Since an IgA antibody response occurs in only approximately 50% of infected children, the actual infection rate in our cohort is estimated to approximately 10......%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  15. Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Walter Strobl

    2015-05-01

    Full Text Available Botulinum toxin A (BoNT-A is considered a safe and effective therapy for children with cerebral palsy (CP, especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.

  16. An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

    Science.gov (United States)

    Alfonsi, E; Merlo, I M; Ponzio, M; Montomoli, C; Tassorelli, C; Biancardi, C; Lozza, A; Martignoni, E

    2010-01-01

    Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

  17. Treatment of hemifacial spasm with botulinum toxin type a: effective, long lasting and well tolerated

    Directory of Open Access Journals (Sweden)

    Jean Pierre Mette Batisti

    Full Text Available ABSTRACT Hemifacial spasm (HFS is a common movement disorder characterized by involuntary tonic or clonic contractions of the muscles innervated by the facial nerve. Objective To evaluate the long-term effect of botulinum toxin type A (BTX-A in the treatment of HFS. Methods A retrospective analysis of patients treated at the Movement Disorders Outpatient Clinic in the Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, from 2009 to 2013 was carried out. A total of 550 BTX-A injections were administered to 100 HFS patients. Results Mean duration of improvement following each injection session was 3.1 months, mean latency to detection of improvement was 7.1 days and mean success rate was 94.7%. Patients were evaluated at an interval of 5.8 months after each application. Adverse effects, which were mostly minor, were observed in 37% of the patients at least once during follow-up. The most frequent was ptosis (35.1%. Conclusion Treatment of HFS with BTX-A was effective, sustainable and safe and had minimal, well-tolerated side effects.

  18. Cyanobacteria, Toxins and Indicators: Field Monitoring,Treatment Facility Monitoring and Treatment Studies

    Science.gov (United States)

    This presentation is a compilation of harmful algal bloom (HAB) related field monitoring data from the 2015 bloom season, treatment plant monitoring data from the 2013 and 2014 bloom seasons, and bench-scale treatment study data from 2015.

  19. [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.

  20. Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

    Science.gov (United States)

    Pourakbari, Babak; Moradi, Behnaz; Mirzaee, Farin; Mahmoudi, Shima; Teymuri, Mostafa; Mamishi, Setareh

    2013-01-01

    Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

  1. Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination

    Science.gov (United States)

    Bart, Marieke J.; Harris, Simon R.; Advani, Abdolreza; Arakawa, Yoshichika; Bottero, Daniela; Bouchez, Valérie; Cassiday, Pamela K.; Chiang, Chuen-Sheue; Dalby, Tine; Fry, Norman K.; Gaillard, María Emilia; van Gent, Marjolein; Guiso, Nicole; Hallander, Hans O.; Harvill, Eric T.; He, Qiushui; van der Heide, Han G. J.; Heuvelman, Kees; Hozbor, Daniela F.; Kamachi, Kazunari; Karataev, Gennady I.; Lan, Ruiting; Lutyńska, Anna; Maharjan, Ram P.; Mertsola, Jussi; Miyamura, Tatsuo; Octavia, Sophie; Preston, Andrew; Quail, Michael A.; Sintchenko, Vitali; Stefanelli, Paola; Tondella, M. Lucia; Tsang, Raymond S. W.; Xu, Yinghua; Yao, Shu-Man; Zhang, Shumin; Mooi, Frits R.

    2014-01-01

    ABSTRACT Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. PMID:24757216

  2. Cyanobacteria Toxin and Cell Propagation through Lake Erie Treatment Facilities - proceedings

    Science.gov (United States)

    Harmful algal blooms (HABs), and their associated toxins, in fresh water lakes and reservoirs are drawing the attention of utilities and state regulators nation-wide. Recognizing the potential health and economic consequences, the US Environmental Protection Agency, in partnersh...

  3. Tridimensional assessment of adductor spasmodic dysphonia pre- and post-treatment with Botulinum toxin.

    Science.gov (United States)

    Dejonckere, P H; Neumann, K J; Moerman, M B J; Martens, J P; Giordano, A; Manfredi, C

    2012-04-01

    Spasmodic dysphonia voices form, in the same way as substitution voices, a particular category of dysphonia that seems not suited for a standardized basic multidimensional assessment protocol, like the one proposed by the European Laryngological Society. Thirty-three exhaustive analyses were performed on voices of 19 patients diagnosed with adductor spasmodic dysphonia (SD), before and after treatment with Botulinum toxin. The speech material consisted of 40 short sentences phonetically selected for constant voicing. Seven perceptual parameters (traditional and dedicated) were blindly rated by a panel of experienced clinicians. Nine acoustic measures (mainly based on voicing evidence and periodicity) were achieved by a special analysis program suited for strongly irregular signals and validated with synthesized deviant voices. Patients also filled in a VHI-questionnaire. Significant improvement is shown by all three approaches. The traditional GRB perceptual parameters appear to be adequate for these patients. Conversely, the special acoustic analysis program is successful in objectivating the improved regularity of vocal fold vibration: the basic jitter remains the most valuable parameter, when reliably quantified. The VHI is well suited for the voice-related quality of life. Nevertheless, when considering pre-therapy and post-therapy changes, the current study illustrates a complete lack of correlation between the perceptual, acoustic, and self-assessment dimensions. Assessment of SD-voices needs to be tridimensional.

  4. Locally Applied Valproate Enhances Survival in Rats after Neocortical Treatment with Tetanus Toxin and Cobalt Chloride

    Directory of Open Access Journals (Sweden)

    Dirk-Matthias Altenmüller

    2013-01-01

    Full Text Available Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT plus cobalt chloride (CoCl2. Methods. In rats, VPA ( or sodium chloride (NaCl ( containing polycaprolactone (PCL implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes. Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (. In both groups, witnessed deaths occurred in the context of seizures. At least of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures. Conclusions. The novel TeT/CoCl2 approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.

  5. Initial North American experience with botulinum toxin type A for treatment of anismus.

    Science.gov (United States)

    Joo, J S; Agachan, F; Wolff, B; Nogueras, J J; Wexner, S D

    1996-10-01

    Botulinum toxin type A (BTX-A), produced by Clostridium botulinum, is a potent neurotoxin. The purpose of this study was to evaluate the efficacy of BTX-A for treatment of anismus. All patients treated with BTX-A for anismus were evaluated. Eligibility criteria included a history of chronic assisted evacuation (laxatives, enemas, or suppositories), demonstration of anismus by cinedefecogram and electromyography, and failure of a minimum of three sessions of supervised biofeedback therapy (BF). Contingent on body mass, 6 to 15 units of BTX-A was injected bilaterally under electromyography guidance into the external sphincter or the puborectalis muscle. Treatment was repeated as necessary for a maximum of three sessions during a three-month period. Success was considered as discontinuation of evacuatory assistance and was evaluated between one and three months and again at up to one year. Between July 1994 and May 1995, four patients ranging from 29 to 82 years in age (2 females, 2 males) had anismus that failed to respond to between 3 and 15 biofeedback sessions. All patients improved between one and three months after BTX-A injection, and two had sustained improvement for a range of three months to one year. There was no morbidity or mortality associated with BTX-A injection. BTX-A is extremely successful for temporary treatment of anismus that is refractory to BF management. However, because the mechanism of action is short, longer term results are only 50 percent successful. Hopefully, modifications in the strain of BTX-A and dose administered will allow longer periods of success or a repeat trial of BF. Nonetheless, this preliminary report is very encouraging in offering a method of managing this recalcitrant condition.

  6. Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye.

    Science.gov (United States)

    Serna-Ojeda, Juan Carlos; Nava-Castaneda, Angel

    2017-03-01

    To evaluate the efficacy of botulinum toxin type A injection to cause orbicularis eyelid muscle paralysis to improve dry eye signs and symptoms. A prospective, randomized, comparative eye-to-eye and interventional study was performed. Patients with dry eye symptoms and positive fluorescein corneal staining were included. Randomly one eyelid received a subcutaneous injection of botulinum toxin in the medial orbicularis muscle portion of the lower eyelid, and the other eye received placebo. The subjective evaluation was achieved with a questionnaire assessing symptoms, quality of vision and ocular comfort level. The objective evaluation included the measurement of the tear film break-up time (TBUT), Schirmer's test and corneal and conjunctival staining. Twenty patients were included with a mean age of 59.5 years. Two weeks after the botulinum toxin injection, all patients showed a decrease in the horizontal movement of the lower eyelid when blinking. The eyes in the active treatment group showed better scores compared with the sham group in four symptoms 4 weeks after the treatment. The TBUT was higher at 1 and 3 months in the active treatment group. The corneal and conjunctival staining were significantly lower in the active treatment group at 1 and 3 months, and the Schirmer's test showed better measurements in the same group at 2 weeks, 1 month and 3 months. There were no adverse events reported. The injection of botulinum toxin A in the medial part of the lower eyelid is an effective and safe procedure that temporally improves some of the signs and symptoms of patients with dry eye. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. 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.

  8. Botulinum toxin treatment of false vocal folds in adductor spasmodic dysphonia: Functional outcomes.

    Science.gov (United States)

    Simpson, C Blake; Lee, Christopher T; Hatcher, Jeanne L; Michalek, Joel

    2016-01-01

    Supraglottic injection of botulinum toxin (Botox) has been described as an effective treatment for adductor spasmodic dysphonia (ADSD). Anecdotal evidence suggests that the patients have little to no breathiness after injection, but no formal longitudinal studies have been carried out to date. The purpose of this study was to examine the voice outcomes in patients with ADSD after supraglottic Botox injection. Retrospective case series. Patients with ADSD who were treated with supraglottic Botox injections completed a qualitative self-evaluation of voice function after injection using the percentage of normal function (PNF) scale, a validated, quantitative scale from 0% (no function) to 100% (normal function). Posttreatment voice improvement after injection was determined using a Voice Handicap Index-10 (VHI-10) questionnaire. A total of 198 supraglottic injections were performed between July 2011 and October 2014. Twenty-five questionnaires were completed. Mean postinjection PNF was 95.0% ± 8.4% and was significantly increased from the preinjection mean PNF (62.5%) ± 22.6% (P < 0.001). The mean best VHI-10 for all injections was 7.23. In 19 of 25 patients (76%), there was no reduction in PNF in the early postinjection period. In the remaining six patients (24%), the decline in mean vocal function was 9.2%. Supraglottic Botox injection is an effective treatment for ADSD. Postinjection voice is significantly improved, and the majority of patients do not experience breathy voice/decline in vocal function after injection. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Cellular and humoral immunity after infection with B. pertussis : the role of age, antigen and vaccination history

    NARCIS (Netherlands)

    van Twillert, I

    2017-01-01

    Pertussis (whooping cough), is a bacterial disease of the respiratory tract, caused by the human pathogen Bordetella pertussis. Vaccination against pertussis has dramatically lowered pertussis incidence and mortality rates; however pertussis still occurs. The duration of immunity to B. pertussis

  10. Cell envelope of Bordetella pertussis: immunological and biochemical analyses and characterization of a major outer membrane porin protein

    International Nuclear Information System (INIS)

    Armstrong, S.K.

    1986-01-01

    Surface molecules of Bordetella pertussis which may be important in metabolism, pathogenesis, and immunity to whooping cough were examined using cell fractionation and 125 I cell surface labeling. Antigenic envelope proteins were examined by immunofluorescence microscopy and Western blotting procedures using monoclonal antibodies and convalescent sera. A surface protein with a high M/sub r/, missing in a mutant lacking the filamentous hemagglutinin, was identified in virulent Bordetella pertussis but was absent in virulent B. pertussis strains. At least three envelope proteins were found only in virulent B. pertussis strains and were absent or diminished in avirulent and most phenotypically modulated strains. Transposon-induced mutants unable to produce hemolysin, dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin also lacked these three envelope proteins, confirming that virulence-associated envelope proteins were genetically regulated with other virulence-associated traits. Two dimensional gel electrophoresis revealed at least five heat modifiable proteins which migrated as higher or lower M/sub r/ moieties if solubilized at 25 0 C instead of 100 0 C

  11. SPECIFIC PERTUSSIS PREVENTION: PROBLEMS AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2007-01-01

    Full Text Available The lecture shows the modern state of the pertussis issue among the children. Based on the analysis of the presented data, the authors conclude that vaccination with the full cellular vaccine is rather safe; moreover, it protects the infants from the severe forms of the disease and lethal outcomes. However, the fact that there are children with constant contraindications to immunization with the full cellular vaccine, the change of the circulating B. pertussis serotypes, morbidity of the older children due to the loss of the postcvaccinal immunity define the necessity to introduce revaccination, as well as they are indications to the wider implementation of the non-cellular pertussis vaccine.Key words: pertussis, children, vaccination, full cellular pertussis vaccine, non-cellular pertussis vaccine.

  12. Real-time PCR-based detection of Bordetella pertussis and Bordetella parapertussis in an Irish paediatric population.

    LENUS (Irish Health Repository)

    Grogan, Juanita A

    2011-06-01

    Novel real-time PCR assays targeting the Bordetella pertussis insertion sequence IS481, the toxin promoter region and Bordetella parapertussis insertion sequence IS1001 were designed. PCR assays were capable of detecting ≤10 copies of target DNA per reaction, with an amplification efficiency of ≥90 %. From September 2003 to December 2009, per-nasal swabs and nasopharyngeal aspirates submitted for B. pertussis culture from patients ≤1 month to >15 years of age were examined by real-time PCR. Among 1324 patients, 76 (5.7 %) were B. pertussis culture positive and 145 (10.95 %) were B. pertussis PCR positive. Of the B. pertussis PCR-positive patients, 117 (81 %) were aged 6 months or less. A total of 1548 samples were examined, of which 87 (5.6 %) were culture positive for B. pertussis and 169 (10.92 %) were B. pertussis PCR positive. All culture-positive samples were PCR positive. Seven specimens (0.5 %) were B. parapertussis culture positive and 10 (0.8 %) were B. parapertussis PCR positive, with all culture-positive samples yielding PCR-positive results. A review of patient laboratory records showed that of the 1324 patients tested for pertussis 555 (42 %) had samples referred for respiratory syncytial virus (RSV) testing and 165 (30 %) were positive, as compared to 19.4 % of the total 5719 patients tested for RSV in this period. Analysis of the age distribution of RSV-positive patients identified that 129 (78 %) were aged 6 months or less, similar to the incidence observed for pertussis in that patient age group. In conclusion, the introduction of the real-time PCR assays for the routine detection of B. pertussis resulted in a 91 % increase in the detection of the organism as compared to microbiological culture. The incidence of infection with B. parapertussis is low while the incidence of RSV infection in infants suspected of having pertussis is high, with a similar age distribution to B. pertussis infection.

  13. Seroprevalence of Bordetella pertussis among vaccinated and unvaccinated pregnant women and newborn infants in a university hospital of Buenos Aires.

    Science.gov (United States)

    Bosch, Juan J; Fernández, Hilaria; Polak, Fernando P; Musante, Gabriel; Libster, Romina; Rocca Rivarola, Manuel

    2017-08-01

    Pertussis is a highly contagious disease caused by Bordetella pertussis. It poses a high morbidity and mortality rate, especially among infants younger than 6 months old. In Argentina, pertussis incidence and mortality have increased over the past three decades. To establish Bordetella pertussisantibody titers among pregnant women in their third trimester and among newborn infants, as measured in cord blood. This was an observational, cross-sectional study. The study started in 2011; at that time, pertussis vaccination was not mandatory for pregnant women as per the national immunization schedule, only optional. Maternal antibodies were measured in the last trimester of pregnancy for women and in cord blood for newborn infants. Antibody titers were determined using Abcam's anti-Bordetella pertussis toxin (PT) IgG in vitro ELISA kit. The χ² test was used to compare prevalence rates. The study included 111 mother-newborn infant dyads; 35 infants from unvaccinated mothers (before the introduction of the vaccine) and 76 from vaccinated mothers. Positive IgG antibodies were found in 92% (70/76) of infants born from vaccinated mothers whereas 100% (35/35) of infants born from unvaccinated mothers had negative results for antibodies; p < 0.001. In the vaccinated population of this study, 92% of infants had positive IgG antibodies. This study supports the need for maternal immunization against Bordetella pertussis to provide protection to newborn infants. Sociedad Argentina de Pediatría

  14. Under-recognized pertussis in adults from Asian countries: a cross-sectional seroprevalence study in Malaysia, Taiwan and Thailand.

    Science.gov (United States)

    Koh, M T; Liu, C-S; Chiu, C-H; Boonsawat, W; Watanaveeradej, V; Abdullah, N; Zhang, Xh; Devadiga, R; Chen, J

    2016-04-01

    Surveillance data on the burden of pertussis in Asian adults are limited. This cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in Malaysia, Taiwan and Thailand. Adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. Single blood samples for anti-pertussis toxin antibodies (anti-PT IgG) were analysed and economic impact and health-related quality of life (EQ-5D) questionnaires assessed. Sixteen (5·13%) of the 312 chronically coughing adults had serological evidence of pertussis infection within the previous 12 months (anti-PT IgG titre ⩾62·5 IU/ml). Three of them were teachers. Longer duration of cough, paroxysms (75% seroconfirmed, 48% non-seroconfirmed) and breathlessness/chest pain (63% seroconfirmed, 36% non-seroconfirmed) were associated with pertussis (P Malaysia, US$83 in Taiwan (n = 1) and US$26 in Thailand. The overall median EQ-5D index score of cases was 0·72 (range 0·42-1·00). Pertussis should be considered in the aetiology of adults with a prolonged or paroxysmal cough, and vaccination programmes considered.

  15. Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

    Science.gov (United States)

    Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

    2010-08-01

    Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

  16. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    Science.gov (United States)

    Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  17. Bordetella pertussis pathogenesis: current and future challenges

    Science.gov (United States)

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  18. Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

    Science.gov (United States)

    Park, Amy J; Paraiso, Marie Fidela R

    2009-08-01

    Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

  19. [Advantages of combined therapies in cosmetic medicine for the treatment of face aging: botulinum toxin, fillers and mesotherapy].

    Science.gov (United States)

    Braccini, F; Dohan Ehrenfest, D M

    2010-01-01

    Non surgical cosmetic medicine procedures for the face are developing considerably, as they deliver good results using simple, non invasive, atraumatic and reproducible techniques. Aesthetic mesotherapy, also known as anti-aging mesotherapy, uses intra-dermal injections of a nutritive and moisturizing solution to improve brightness, skin hydration and tonus, and also smooth out superficial wrinkles. Subcutaneous filler injections enable to fill wrinkles and folds; by using high density products it is also able to provide genuine facial volumetric reconstruction. Finally, botulinum toxin acts by reducing certain muscle contractions to smooth out expression lines and folds induced by facial dynamics. In this article, we explore the concept of combined therapy and describe our experience associating anti-aging mesotherapy (NCTF-135HA, Filorga, Paris, France), hyaluronic acid based fillers (X-HA3 and X-HA-Volume, Filorga, Paris, France) and botulinum toxin (Vistabel, Allergan, Irvine CA, USA). A therapy combining anti-aging mesotherapy, botulinum toxin and filler injections, offers full treatment of the 3 biological levels of the covering tissues. This non-invasive therapeutic strategy brings patient satisfaction through a global approach to facial aging.

  20. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Directory of Open Access Journals (Sweden)

    Domenico Intiso

    2015-06-01

    Full Text Available Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders

  1. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Science.gov (United States)

    Intiso, Domenico; Basciani, Mario; Santamato, Andrea; Intiso, Marta; Di Rienzo, Filomena

    2015-01-01

    Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post

  2. Coley's toxin and BCG vaccine in prevention and treatment of malignant melanoma in humans

    Czech Academy of Sciences Publication Activity Database

    Kučerová, Petra; Vlasáková, Jitka; Červinková, Monika

    2017-01-01

    Roč. 28, č. 3 (2017), s. 124-128 ISSN 0954-139X R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : BCG vaccine * Coley´s toxin * cytokines Subject RIV: EC - Immunology OBOR OECD: Immunology

  3. Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

    Science.gov (United States)

    Visco, Anthony G; Brubaker, Linda; Richter, Holly E; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

    2012-01-01

    This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Epizootic pertussis focus of hamadryad baboons

    Directory of Open Access Journals (Sweden)

    A. Yu. Medkova

    2015-01-01

    Full Text Available The absence of an adequate experimental animal model makes difficult study of immunity against whooping cough and its pathogenesis. Experimental whooping cough reported by us earlier in pubescent non-human primates of the Old World was accompanied by specific clinical and laboratory marks in the absence of cough. The possibility of pertussis modelling while experimental whooping cough in impuberal hamadryad baboons was investigated. In the process of selection of monkeys for the further studies for perfecting of experimental model for pertussis research unexpectedly were detected specific pertussis antibodies in impuberal hamadryad baboons.The aim of the study: revealing of source of infection and transmission of pertussis to hamadryad baboons and investigation of response of antibody-positive impuberal hamadryad baboons to secondary contagion by B. pertussis bacteria while experimental infection.Results. 18 veterinary checked, somatically healthy hamadryad baboons of various gender managed in two neighboring cages. Specific pertussis IgM and IgG antibodies were found in blood serum of all the animals and one of the monkey keepers. By real-time PCR in nasopharyngeal swabs of the monkey keeper and three 7- and 9-month-old hamadryad baboons were registered single B. pertussis genom equivalents. Seropositive impuberal hamadryad baboons were experimentally challenged by virulent B. pertussis 475 strain. Quantity of B. pertussis genom equivalents and percentage of IgM and IgG antibodies in impuberal hamadryad baboons after experimental infection were detected. These results were comparable with such received after secondary experimental challenge of monkeys by B. pertussis. Humoral immuneresponse was characterized by booster effect and rapid B. pertussis elimination.Conclusion. The case of transmission of B.pertussis bacteria to hamadryad baboons by natural contagion and epizootic focus of pertussis in apery conditions

  5. Characterizing RecA-independent induction of Shiga toxin2-encoding phages by EDTA treatment.

    Directory of Open Access Journals (Sweden)

    Lejla Imamovic

    Full Text Available BACKGROUND: The bacteriophage life cycle has an important role in Shiga toxin (Stx expression. The induction of Shiga toxin-encoding phages (Stx phages increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. METHODOLOGY/PRINCIPAL FINDINGS: The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage λ induction (RcsA and DsrA were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg(2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. CONCLUSIONS/SIGNIFICANCE: Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon of induction and release of Stx phages as an important factor in the pathogenicity of Shiga toxin-producing Escherichia coli (STEC and in the emergence of new pathogenic strains.

  6. Effect of radio treatment with gamma radiation on the decontamination and cytotoxicity of a myco toxin: Ochratoxin A

    International Nuclear Information System (INIS)

    Mehrez, Amel

    2008-01-01

    solution. When irradiated on millet flour, the toxin level was significantly reduced by 48 and 62 % at a dose level of 2 and 4 KGy, respectively. However, in solution, OTA at concentrations of 1 and 5 ppm, was relatively stable even at dose level of 4 kGy and did not cause the formation of degradation products neither detectable by HPLC-FD nor by LC-MS . For toxicity evaluations, first preliminary cell culture assays were performed with the irradiated toxin. Using human hepatocytes Hep G2 cells, OTA-induced cytotoxicity is monitored at several levels in these cells after radio treatment. The irradiation of the toxin led to a non marked changes in its cytotoxicity. These findings indicate that the use of low dose gamma irradiation to destroy preformed toxins presents on grain does not appear to be a suitable method for the detoxification of grain contaminated with OTA. Therefore, the prevention of toxin formation still the best protection way against ochratoxin A contamination. (Author)

  7. Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults--a review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience.

    Science.gov (United States)

    Thierry-Carstensen, Birgit; Dalby, Tine; Stevner, Michael A; Robbins, John B; Schneerson, Rachel; Trollfors, Birger

    2013-10-25

    Combination vaccines containing a monocomponent acellular pertussis (aP) vaccine, manufactured at Statens Serum Institut (SSI), Denmark, have successfully controlled Bordetella pertussis infections in Denmark since 1997. The efficacy of this aP vaccine was 71% in a double-blind, randomised and controlled clinical trial. Its safety and immunogenicity have been demonstrated in infants, children, adolescents and adults. In approximately 500,000 children it was effective against pertussis requiring hospitalisation (VE: 93% after 3 doses) and against pertussis not requiring hospitalisation (VE: 78% after 3 doses). IgG antibodies against pertussis toxin (IgG anti-PT) response rates after booster vaccination of adults with tetanus, diphtheria and aP combination vaccine (TdaP) were considerably higher for this monocomponent aP vaccine containing 20μg pertussis toxoid, inactivated by hydrogen peroxide (92.0%), than for two multicomponent aP vaccines inactivated by formaldehyde and/or glutaraldehyde: 3-component aP with 8μg pertussis toxoid (77.2%) and 5-component aP with 2.5μg pertussis toxoid (47.1%), without compromising the safety profile. In Denmark where this monocomponent aP vaccine has been the only pertussis vaccine in use for 15 years, there has been no pertussis epidemic since 2002 (population incidence 36 per 100,000), in contrast to neighbouring countries, where epidemics have occurred. This monocomponent aP vaccine can be used in combination vaccines for primary and booster vaccination against pertussis in all age groups and is an important tool for successful pertussis control. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review.

    Science.gov (United States)

    Emile, Sameh Hany; Elfeki, Hossam Ayman; Elbanna, Hosam Ghazy; Youssef, Mohamed; Thabet, Waleed; Abd El-Hamed, Tito M; Said, Basem; Lotfy, Ahmed

    2016-08-06

    To evaluate the efficacy and safety of botulinum toxin type A (BTX-A) in the management of patients with anismus. An organized search of published literature was conducted using electronic databases including: PubMed/MEDLINE, and Cochrane Central Register of Controlled Trials, also an internet-based search using "Google Scholar" service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and long-term clinical improvement, post-injection changes in electromyography (EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection. Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU (range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonography-guided technique, one study used EMG-guided technique, whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4% (range 37.5%-86.7%), this percentage declined to a median of 46% (range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between (37.5%-80%), (54%-86.7%), and (25%-86.6%), respectively. Fourteen (7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. Initial satisfactory improvement of symptoms after BTX-A injection remarkably deteriorated after 3 mo of the

  9. Purification of heat labile toxin from Bordetella pertussis vaccine ...

    African Journals Online (AJOL)

    K.C. Shivanandappa

    2015-06-23

    Jun 23, 2015 ... heat inactivation at 56 °C for 30 min during Wcpv prepara- tion. Therefore, the ... The B2 culture medium was prepared with following composi- tions: Bacto casamino ... 15min at the ambient temperature (+18 to 22 °C). The.

  10. The course of cervical dystonia with head tremor during botulinum toxin type A treatment

    Directory of Open Access Journals (Sweden)

    A. N. Korenko

    2017-01-01

    Full Text Available Objective: to evaluate the efficacy and safety of botulinum toxin type A (BTA injections into the neck muscles to reduce dystonic postures, head tremor, and pain syndrome in patients with cervical dystonia (CD within the first 8 cycles of treatment.Patients and methods. The investigation included 76 patients (26 (34% men and 50 (66% women with CD and dystonic head tremor, who were given BTA injections into the neck muscles for the first time. All the 76 patients received at least one cycle of BTA therapy. At the same type, 18 of these patients received 4 cycles of injections and 36 patients had 8 cycles. Injections were given when the symptoms of CD recurred or increased and the patient needed to be retreated. The interval between the injection cycles was arbitrary, but not less than 12 weeks. The doses of BTA agents per treatment cycle were as follows: Dysport was 400 to 1000 U, xeomin was 50 to 300 U, and Botox 200 to 300 U. The symptoms of CD were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS and the Tsui scale before the first injection of BTA and injection cycles 4 and 8; the presence or absence of head tremor was recorded.Results. The TWSTRS severity of CD symptoms decreased from 38 [36; 41] to 30 [27; 33] scores by injection cycle 4 (p < 0.001 and to 26 [23; 27] scores by cycle 8 (p<0.01. The Tsui severity of CD reduced from 9.3 [9; 10] to 7.2 [7; 8] scores by injection cycle 4 (p<0.001 and to 6.7 [6; 7] scores by cycle 8. The Tsui tremor scores decreased from 1.9 [1.6; 2.1] to 1.4 [1.1; 1.6] scores by injection cycle 4 and to 1.1 [0.9;1.4] scores by cycle 8 (p<0.01. Tremor completely disappeared in 6 (11% of patients by injection cycle 4 and in 6 (18% patients by cycle 8. According to Section 3 of the TWSTRS, pain intensity was reduced from 9.9 [8.9; 11.0] to 5.0 [3.3; 6.6] scores by injection cycle 4 (p<0.001 and to 2.1 [0.7; 3.6] scores by cycle 8 (p < 0.01; pain regressed completely in 12 (41

  11. Maternal vaccination to prevent pertussis in infants

    African Journals Online (AJOL)

    2016-09-09

    Sep 9, 2016 ... that maternal immunisation with the Tdap (tetanus, diphtheria and acellular pertussis) vaccine is safe. Indeed, maternal vaccination is now recommended to prevent pertussis infection in vulnerable young infants. In the USA and UK, the immunisation of pregnant women with a Tdap or dTaP/IPV (diphtheria, ...

  12. Effect of relevant culture parameters on Pertussis toxin expression by Bordetella pertussis

    NARCIS (Netherlands)

    Thalen, M.; Venema, M.; IJssel, van den J.; Berwald, L.; Beuvery, E.C.; Martens, D.E.; Tramper, J.

    2006-01-01

    Whooping cough vaccines are produced using different ranges of cultivation conditions and medium compositions, which are known to influence growth rate, virulence factor production and degradation, as well as the virulence factors' association to the cell. This study quantifies the impact of

  13. [Pertussis (Whooping cough)--an update].

    Science.gov (United States)

    Stock, Ingo

    2015-12-01

    Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy.

  14. Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients.

    Science.gov (United States)

    Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi

    2013-01-01

    Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

  15. [Features of Bordetella pertussis, Bordetella spp. infection and whopping cough in Córdoba province, Argentina].

    Science.gov (United States)

    Giayetto, Víctor O; Blanco, Sebastián; Mangeaud, Arnaldo; Barbás, María G; Cudolá, Analía; Gallego, Sandra V

    2017-04-01

    Whooping cough is a re-emerging infection in the world and Latin America. It was considered relevant to investigate the clinical and epidemiological profile of Bordetella spp. and Bordetella pertussis infection in Córdoba province, Argentina; evaluating, at the same time, the co-infection with virus producing respiratory infections that may be confused with whooping cough. All whooping cough suspected cases were studied by Polimerase Chain Reaction, amplifying the repeated insertion sequence (IS) 481 and the promoter gene encoding pertussis toxin, between 2011 and 2013. The data were obtained from the clinical and epidemiological records. From 2,588 whooping cough suspected cases, 11.59% was infected by Bordetella spp. and 9.16% was confirmed as Bordetella pertussis infection. The rate of infection was 7.22 and 1.84 per 100,000 for 2011 and 2012, respectively. The infection presented a seasonal tendency and it was mainly found on the group of children between 13 and 24 months old. The co-infection with virus producing respiratory infections, were uncommon. Paroxysmal cough, cyanosis and/or vomiting were predictors of the infection for Bordetella pertussis. To deal with the re-emergence of whooping cough is important the knowledge of the regional epidemiological situation. This paper shows the situation of these infections in the regional clinical and epidemiological context, and makes the information available for health decision-making.

  16. Epidemiologic Overview of Synkinesis in 353 Patients with Longstanding Facial Paralysis under Treatment with Botulinum Toxin for 11 Years.

    Science.gov (United States)

    Salles, Alessandra Grassi; da Costa, Eduardo Fernandes; Ferreira, Marcus Castro; Remigio, Adelina Fatima do Nascimento; Moraes, Luciana Borsoi; Gemperli, Rolf

    2015-12-01

    Patients with longstanding facial paralysis often exhibit synkinesis. Few reports describe the prevalence and factors related to the development of synkinesis after facial paralysis. Botulinum toxin type A injection is an important adjunct treatment for facial paralysis-induced asymmetry and synkinesis. The authors assessed the clinical and epidemiologic characteristics of patients with sequelae of facial paralysis treated with botulinum toxin type A injections to evaluate the prevalence of synkinesis and related factors. A total of 353 patients (age, 4 to 84 years; 245 female patients) with longstanding facial paralysis underwent 2312 botulinum toxin type A injections during an 11-year follow-up. Doses used over the years, previous treatments (electrical stimulation, operations), and how they correlated to postparalysis and postreanimation synkinesis were analyzed. There was a significant association between cause and surgery. Most patients with facial paralysis caused by a congenital defect, trauma, or a tumor underwent reanimation. There were no sex- or synkinesis-related differences in the doses used, but the doses were higher in the reanimation group than in the no-surgery group. Synkinesis was found in 196 patients; 148 (41.9 percent) presented with postparalysis synkinesis (oro-ocular, oculo-oral) and 58 (16.4 percent) presented with postreanimation synkinesis. Ten patients presented with both types. This study determined the high prevalence (55.5 percent) of synkinesis in patients with longstanding facial paralysis. Postparalysis synkinesis was positively associated with infectious and idiopathic causes, electrical stimulation, facial nerve decompression, and no requirement for surgery. Postreanimation synkinesis was present in 28.2 percent of reanimated patients and was significantly associated with microsurgical flaps, transfacial nerve grafting, masseteric-facial anastomosis, and temporalis muscle transfers.

  17. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

    2018-02-01

    To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

  18. [Medical care of patients with spasticity following stroke : Evaluation of the treatment situation in Germany with focus on the use of botulinum toxin].

    Science.gov (United States)

    Kerkemeyer, L; Lux, G; Walendzik, A; Wasem, J; Neumann, A

    2017-08-01

    Upper limb spasticity is a common complication following stroke. Cohort studies found 19% of post-stroke patients had upper limb spasticity at 3 months and 38% of patients at 12 months. For focal spasticity, intramuscular injections of botulinum toxin are indicated. In Germany, it is assumed that patients with the described indication are undersupplied with botulinum toxin. The aim of the present study is to evaluate the medical care of patients with upper limb spasticity post-stroke with the focus on the use of botulinum toxin as one treatment option. A standardized questionnaire was developed and a postal survey of a representative national random sample of 800 neurologists to capture the actual medical care situation. The response rate amounted to 37% (n = 292). 59% of the neurologists surveyed had never used botulinum toxin. In total, 87% of neurologists noticed barriers regarding the use of botulinum toxin, where the amount of the doctor's remuneration in 40% and the lack of reimbursement of costs in off-label use in 60% were the most commonly used answers. The achievement of an advanced training in using botulinum toxin was also stated as a general obstacle for resident neurologists. Due to a response rate of 37% for the postal survey a selection bias cannot be excluded. Although botulinum toxin is recommended in the national treatment guidelines, many neurologists do not use botulinum toxin. The reasons can be seen from the barriers described.

  19. Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.

    Science.gov (United States)

    Caboré, Raïssa Nadège; Maertens, Kirsten; Dobly, Alexandre; Leuridan, Elke; Van Damme, Pierre; Huygen, Kris

    2017-10-03

    Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.

  20. The use of botulinum toxin in the treatment of the consequences of bruxism on cervical spine musculature.

    Science.gov (United States)

    Finiels, P J; Batifol, D

    2014-03-01

    Hypertonia and hyperactivity of masticatory muscles are involved in pain and contractions of the cervical spine musculature, but their pathophysiology remains nonetheless unknown and its treatment far to be codified. In this study, 8 patients, showing disabling posterior neck muscle contractures linked with bruxism were prospectively treated and followed for an average 15 months period, after having received Injections of botulinum toxin A essentially in masticatory muscles. Injections were made every 3 months, varying from 10 to 100 U Botox* by muscles, without administrating more than 300 U Botox* in the same patient. The angle of cervical lordosis were calculated on lateral sitting radiographs in neutral position, good results being considered to be achieved in the case of a 2 point diminution of VAS score as well as at least a 5° positive gain in the curve. 7 patients out of 8 showed a real improvement in their symptoms after an average of 3 injections, showing a decrease of 4.5 points on the VAS score and an average increment of 15° in cervical lordosis. Although the follow-up period of patients was relatively short and the sample quite small, the general impression, confirmed by the patients' experience, seems to suggest a potential place for the use of botulinum toxin amongst the array of treatments which can be offered in certain selected cases which associate bruxism and posterior cervical contractions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. The Effect of Total Cumulative Dose, Number of Treatment Cycles, Interval between Injections, and Length of Treatment on the Frequency of Occurrence of Antibodies to Botulinum Toxin Type A in the Treatment of Muscle Spasticity

    Science.gov (United States)

    Bakheit, Abdel Magid O.; Liptrot, Anthea; Newton, Rachel; Pickett, Andrew M.

    2012-01-01

    A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these…

  2. Growth factor toxin fusion proteins for the treatment of leukemia: Preclinical animal studies relevant for human acute myeloid leukemia

    NARCIS (Netherlands)

    H. Rozemuller (Henk)

    1997-01-01

    textabstractIn the development of new therapeutic agents to treat malignancies. bacterial and plant toxins are being investigated. Targeting cells with these toxins has been facilitated by chemical conjugation or genetic engineering of the toxin to proteins with cellular binding potential, such as

  3. Retinal haemorrhage in infants with pertussis.

    Science.gov (United States)

    Raoof, Naz; Pereira, Susana; Dai, Shuan; Neutze, Jocelyn; Grant, Cameron Charles; Kelly, Patrick

    2017-12-01

    It has been hypothesised that paroxysmal coughing in infantile pertussis (whooping cough) could produce retinal haemorrhages identical to those seen in abusive head trauma. We aimed to test this hypothesis. This is a prospective study of infants hospitalised with pertussis in Auckland, New Zealand, from 2009 to 2014. The clinical severity of pertussis was categorised. All infants recruited had retinal examination through dilated pupils by the paediatric ophthalmology service using an indirect ophthalmoscope. Forty-eight infants with pertussis, aged 3 weeks to 7 months, were examined after a mean of 18 days of coughing. Thirty-nine had severe pertussis and nine had mild pertussis. All had paroxysmal cough, and all were still coughing at the time of examination. No retinal haemorrhages were seen. We found no evidence to support the hypothesis that pertussis may cause the pattern of retinal haemorrhages seen in abusive head trauma in infants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Serodiagnosis of whooping cough in Belgium: results of the National Reference Centre for Bordetella pertussis anno 2013.

    Science.gov (United States)

    Duterme, Sophie; Vanhoof, Raymond; Vanderpas, Jean; Pierard, Denis; Huygen, Kris

    2016-04-01

    Report on the pitfalls of serodiagnosis of pertussis in Belgium for 2013 by the NRC Bordetella. Determine cases of acute infection using an anti-pertussis toxin (PT) IgG antibody ELISA. A total of 2471 serum samples were received. Clinical information on the duration of cough (at moment of blood sampling) is essential for a reliable interpretation of the results. In order to avoid false negative results, 213 samples for which this information was lacking were not tested. For a total of 2179 patients tested, 520 (23.9%) had antibody levels indicative of an acute infection, 261 (12%) samples were diagnosed as positive (indicative of a pertussis infection or vaccination during the last year), 143 (6.7%) samples were classified as doubtful and 752 (34,5%) (35.5%) were diagnosed as negative. The serodiagnosis of pertussis has limited value for the early diagnosis of the disease and PCR analysis on nasopharyngeal swabs is the method of choice during the first 2 weeks and always for young children pertussis, serum samples should preferentially be collected 3 weeks after onset of symptoms.

  5. The use of botulinum toxin A in the treatment of functional epiphora.

    Science.gov (United States)

    Whittaker, Karl W; Matthews, Bethan N; Fitt, Alan W; Sandramouli, S

    2003-09-01

    The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora. A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary. Botulinum toxin A (2.5-5 units) was injected into the palpebral lobe of the lacrimal gland on the worst affected side via a transconjunctival approach under topical anaesthesia. Patients underwent a Schirmer test and provided a subjective evaluation of their epiphora symptoms, indoors and outdoors, at baseline and at 1, 4 and 13 weeks after injection. The mean score for symptoms indoors and outdoors was calculated. Fourteen patients agreed to take part in the study. Subjective epiphora scores improved in 8 out of the 11 patients (72.7%) who completed 13 weeks of follow-up. Schirmer test results showed objective reduction in tearing from baseline but did not strongly correlate with the subjective epiphora scores. Transient mild ptosis and diplopia were experienced by two patients. The results from this small pilot study are encouraging, although larger, controlled trials are needed to assess the optimal dose of BTX-A, its long-term efficacy and safety, and the role of multiple injections.

  6. Influence of bacterial toxins on the GTPase activity of transducin from bovine retinal rod outer segments

    International Nuclear Information System (INIS)

    Rybin, V.O.; Gureeva, A.A.

    1986-01-01

    The action of cholera toxin, capable of ADP-ribosylation of the activator N/sub s/ protein, and pertussis toxin, capable of ADP-ribosylation of the inhibitor N/sub i/ protein of the adenylate cyclase complex, on transducin, the GTP-binding protein of the rod outer segments of the retina, was investigated. It was shown that under the action of pertussis and cholera toxins, the GTPase activity of transducin is inhibited. Pertussin toxin inhibits the GTPase of native retinal rod outer segments by 30-40%, while GTPase of homogeneous transducin produces a 70-80% inhibition. The action of toxins on transducin depends on the presence and nature of the guanylic nucleotide with which incubation is performed. On the basis of the data obtained it is suggested that pertussis toxin interacts with pretransducin and with the transducin-GDP complex, while cholera toxin ADP-ribosylates the transducin-GTP complex and does not act on transducin lacking GTP

  7. SNP-based typing: a useful tool to study Bordetella pertussis populations.

    Directory of Open Access Journals (Sweden)

    Marjolein van Gent

    Full Text Available To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA. In this study, a single nucleotide polymorphism (SNP typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in The Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis.

  8. SNP-Based Typing: A Useful Tool to Study Bordetella pertussis Populations

    Science.gov (United States)

    van der Heide, Han G. J.; Heuvelman, Kees J.; Kallonen, Teemu; He, Qiushui; Mertsola, Jussi; Advani, Abdolreza; Hallander, Hans O.; Janssens, Koen; Hermans, Peter W.; Mooi, Frits R.

    2011-01-01

    To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in the Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis. PMID:21647370

  9. Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study.

    Science.gov (United States)

    Li, Xiaomei; Chen, Meng; Zhang, Tiegang; Li, Juan; Zeng, Yang; Lu, Li

    2015-01-01

    The aim of this study was to assess the level of humoral immunity against diphtheria and pertussis by measuring IgG to diphtheria toxoid (DT) and pertussis toxin (PT) in general population of Beijing. A total of 2147 subjects aged 0-74 y were selected with a random sample of resident population in Beijing. The information of socio-demographic characteristics, vaccination history, disease history of diphtheria and pertussis were collected for each subject by questionnaire. Serum samples were tested for IgG antibodies to DT and PT by using commercial ELISA kits. The overall positivity rate of anti-DT IgG was 66.28% with the mean concentration of 2.169 IU/ml. Age stratified data showed that the highest positivity rate of 97.63% was observed in 1-4 y and the rates decreased with age. The positivity rates were only around 50% or below since 25 y old. The positivity rate of anti-PT IgG was 12.34% with the mean concentration of 15.163 IU/ml. The highest level of positivity rate (22.23%) and antibody level (23.101 IU/ml) was seen in diphtheria was observed at 1 y and 6 y respectively, which was consistent with the current immunization schedule. But there was no significant increase of immunity to pertussis observed after booster immunization at 18-24 months, but the proportions of undetectable were lowest in diphtheria and all the age groups showed a low immunity to pertussis indicating the potential risk of transmission and outbreaks of the 2 diseases in Beijing.

  10. 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...

  11. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... hiv/aids overview current news labs links & resources hpv overview why vaccinate posters buttons and banners videos ... q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room ...

  12. Whooping Cough (Pertussis) - Fact Sheet for Parents

    Science.gov (United States)

    ... months 4 through 6 years Fact Sheet for Parents Color [2 pages] Español: Tosferina (pertussis) The best ... according to the recommended schedule. Fact Sheets for Parents Diseases and the Vaccines that Prevent Them Chickenpox ...

  13. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... getvaxed about GETVAXED print ads go to GETVAXED.ORG cme Immunizations Pertussis (Whooping Cough) One family's struggles ... free-of-charge. Branded videos contain the "PKIDs.ORG" end slate; unbranded videos are provided for organizations ...

  14. NNDSS - Table II. Meningococcal to Pertussis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal to Pertussis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  15. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... poster infectious disease workshop links & resources personal items standard precautions travel in health immunizations about immunizations current ... hepatitis report someone you know has hbv/hcv standard precautions Silence the Sounds of Pertussis spokespeople who ...

  16. NNDSS - Table II. Meningococcal disease to Pertussis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal disease to Pertussis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  17. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids infect ... vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles ...

  18. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... freed meet keri russell posters grand article rich media video/audio pneumonia tb overview links & resources families ... hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. ...

  19. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects.

    Science.gov (United States)

    Rath, Judith J G; Tavy, Dénes L J; Wertenbroek, Agnes A A C M; van Woerkom, Theodoor C A M; de Bruijn, Sebastiaan F T M

    2010-08-01

    To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects. Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years. BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

  20. Botulinum toxin for the treatment of motor imbalance in obstetrical brachial plexus palsy.

    Science.gov (United States)

    Arad, Ehud; Stephens, Derek; Curtis, Christine G; Clarke, Howard M

    2013-06-01

    Residual muscle imbalance is a common problem affecting obstetrical brachial plexus palsy patients. The goal of this study was to examine the efficacy of botulinum toxin type A (Botox) in improving this muscle imbalance. The authors retrospectively reviewed obstetrical brachial plexus palsy patients treated with Botox for muscle imbalance as an isolated procedure. Outcomes were the change in Active Movement Scale scores from pre-Botox scores to scores at 1 month after Botox and 1 year after Botox. Twenty-seven patients were included, 19 treated for shoulder imbalance and eight treated for elbow imbalance. Active Movement Scale scores (mean±SD) for shoulder external rotation improved from 0.6±1.0 before Botox to 2.6±2.14 (pimbalance produces improvement in external rotation that is not sufficiently sustained over time to be of clinical benefit. However, Botox for elbow movement imbalance produces a sustained and clinically useful improvement. Therapeutic, IV.

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

    Science.gov (United States)

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

    2006-04-01

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

  2. Association of onabotulinum toxin A treatment with salivary pH and dental caries of neurologically impaired children with sialorrhea.

    Science.gov (United States)

    Ferraz Dos Santos, Beatriz; Dabbagh, Basma; Daniel, Sam J; Schwartz, Stephane

    2016-01-01

    Sialorrhea is a common manifestation of several neurological disorders. The use of intraglandular onabotulinum toxin A (OBTXA) injection has been recognized to effectively treat sialorrhea. As OBTXA injection reduces salivary flow rate and alters salivary quality, its use may have a detrimental effect on oral health. To examine the effect of OBTXA injection on caries experience and salivary pH of neurologically impaired children with sialorrhea. Twenty-five children receiving OBTXA treatment and 25 control children were enrolled in the study. Whole saliva was collected to determine salivary pH. All participants underwent an interview on their dietary habits. Dental clinical examinations were carried out to evaluate caries experience and oral hygiene level. Overall, mean salivary pH value was significantly lower in the OBTXA group (6.92 ± 0.77) compared with the control group (7.36 ± 0.70). Caries activity was significantly higher in the OBTXA group (P = 0.01). The regression analyses showed a significant association between OBTXA treatment and salivary pH value (P = 0.03). Results from the logistic regression show that dental caries was significantly associated with OBTXA treatment (OR = 1.73, CI = 1.14-27.3). The study showed an intricate relationship between OBTXA treatment and oral findings. Hence, special dental care should be given to children receiving OBTXA treatment. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Hyperhidrosis Substantially Reduces Quality of Life in Children: A Retrospective Study Describing Symptoms, Consequences and Treatment with Botulinum Toxin

    Directory of Open Access Journals (Sweden)

    Sandra Eriksson Mirkovic

    2017-09-01

    Full Text Available Studies on children with hyperhidrosis are sparse. This retrospective study presents clinical data and quality of life, along with treatment effect and safety of botulinum toxin (BTX. Case reports from 366 children were included to capture the medical history of hyperhidrosis. The total median score of the Dermatology Life Quality Index before treatment was 11 for children aged 16–17 years and 12 for children younger than 16 years. The children described physical, psychosocial and consequence-related symptoms. More than 70% had multifocal hyperhidrosis. BTX-A and/or BTX-B were given to 323 children, 193 of whom received repeated treatments. The highest score in a 5-grade scale concerning treatment effect was reported by 176/193 children, i.e. their “sweating disappeared completely”. No severe adverse events occurred. Focal and multifocal hyperhidrosis in children reduces quality of life considerably. Treatment with BTX-A and/or BTX-B has been performed with success.

  4. Report of the Task Force on Pertussis and Pertussis Immunization--1988.

    Science.gov (United States)

    American Academy of Pediatrics, Elk Grove Village, IL.

    Pertussis is a severe epidemic and endemic disease with significant morbidity and mortality. The use of whole-cell pertussis vaccines in the United States has been effective in controlling the disease but not in decreasing the circulation of the organism. Whole-cell vaccines commonly cause reactions in children, and in addition, they are often…

  5. Isosorbide dinitrate ointment vs botulinum toxin A (Dysport®) as the primary treatment for chronic anal fissure: a randomized multicentre study

    NARCIS (Netherlands)

    Berkel, A.E.M.; Rosman, C.; Koop, R.; van Duijvendijk, P.; van der Palen, Jacobus Adrianus Maria; Klaase, J.M.

    2014-01-01

    Aim Nitric oxide donors, such as isosorbide dinitrate ointment (ISDN), are considered as first-choice agents in the treatment of chronic anal fissure. Injection with botulinum toxin A in the internal anal sphincter is often used as a second-line therapy, although it may give better results and fewer

  6. The Profile of Patients and Current Practice of Treatment of Upper Limb Muscle Spasticity with Botulinum Toxin Type A: An International Survey

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31…

  7. 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.

  8. Impact of infant and preschool pertussis vaccinations on memory B-cell responses in children at 4 years of age.

    Science.gov (United States)

    Hendrikx, Lotte H; de Rond, Lia G H; Oztürk, Kemal; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-08-05

    Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age. Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation, memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin and pertactin. Before and after the booster, higher memory B-cell responses were measured in aP primed children compared with wP primed children. In contrast with antibody levels, no dose-effect was observed on the numbers of memory B-cell responses. In aP primed children a fifth high-dose aP vaccination tended to induce even lower memory B-cell responses than a low-dose aP booster. In both wP and aP primed children, the number of memory B-cells increased after the booster and correlated with the pertussis-specific antibody concentrations and observed affinity maturation. This study indicates that aP vaccinations in the first year of life induce higher pertussis-specific memory B-cell responses in children 4 years of age compared with Dutch wP primary vaccinations. Since infant aP vaccinations have improved protection against whooping cough in children despite waning antibody levels, this suggests that an enhanced memory B-cell pool induction may have an important role in protection. However, the pertussis-dose of the preschool booster needs to be considered depending on the vaccine used for priming to optimize long-term protection against whooping cough. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Bacillus anthracis Edema Toxin Inhibits Staphylococcus aureus Enterotoxin B Effects in Vitro: A Potential Protein Therapeutic?

    Science.gov (United States)

    2005-10-01

    5). Inherent characteristics of edema toxin and other procaryotic adenylate cyclases from Bordetella pertussis, Pseudomonas aeruginosa, and Yersinia...by mouse peritoneal macrophages: the role of cellular cyclic AMP. Immunology 64:719–724. 12. Krakauer, T. 1999. Induction of CC chemokines in human

  10. An Open Study of Botulinum-A Toxin Treatment of Idiopathic Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Karim Nikkhah

    2015-07-01

    Full Text Available Introduction: Trigeminal Neuralgia (TN is a unilateral, recurrent, sharp facial pain disorder that is limited to the distribution of divisions of the trigeminal nerve. The aim of this study was to evaluate the efficacy of Botulinum neurotoxin type A (BTX-A for alleviating the frequency and severity of TN pain. Materials and Methods: This trial was performed as a before and after study. We treated 31 patients (15 male and 16 female with mean age of 52 year old that their diagnosis was made at least 4.5 years before. We injected BTX-A in various parts of face and particularly in the origin of mandibular and maxillary branches of trigeminal nerve. Injection volume was determined by the necessity and pain intensity measured with visual analog scale up to 100U. Patients were evaluated before and after the injection and were followed after week, and each month, for a three months period. Other related variables were recorded such as: toxin complications, pain status variations by brushing, chewing, cold weather and patient’s satisfaction with their therapy. Results: showed that after injection, pain intensity and frequency decreased after tooth brushing, chewing and cold weather (P

  11. Considerations for initial dosing of botulinum toxin in treatment of adductor spasmodic dysphonia.

    Science.gov (United States)

    Rosow, David E; Parikh, Punam; Vivero, Richard J; Casiano, Roy R; Lundy, Donna S

    2013-06-01

    To assess the effect on voice improvement and duration of breathiness based on initial dose of onabotulinum toxin A (BTX-A) in the management of adductor spasmodic dysphonia (SD) and to compare voice outcomes for initial bilaterally injected doses of 1.25 units (group A) vs 2.5 units (group B) of BTX-A. Case series with chart review of patients with adductor SD treated at a tertiary care facility from 1990 to 2011. Academic subspecialty laryngology practice. Demographic data (age and sex), voice rating, duration of voice improvement, and breathiness were evaluated and compared between groups A and B using the Student t test and χ(2) analysis. Of 478 patients identified, 305 (223 in group A, 82 in group B) patients met inclusion criteria. The average age was 56.2 years in group A and 57.4 years in group B (P = .5). The female to male ratio was 2.91 for group A vs 3.56 for group B (P = .61). Good voice outcomes (grade 3 or 4) were reported by 91% of group A patients vs 94% of group B (P = .75). The average duration of voice improvement was 99.7 days for group A and 108.3 days for group B (P = .54). The average duration of breathiness was 10.88 days for group A vs 15.42 days for group B (P = .02). Patients injected with 1.25 units bilaterally had a statistically significant shorter duration of breathiness without a statistically significant difference in clinical effectiveness or voice outcome. It is therefore recommended that a relatively low initial BTX-A dose be used with subsequent titration to achieve improved voice outcomes.

  12. 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.

  13. Induction and maintenance of Bordetella pertussis specific immune responses

    NARCIS (Netherlands)

    Stenger, R.M.

    2010-01-01

    Pertussis, also referred to as whooping cough, is a serious respiratory disease mainly caused by the gram-negative bacterium Bordetella pertussis. The disease is most severe in neonates and children under the age of 1. Before childhood vaccination was introduced in the 1950s, pertussis was an

  14. Clinical presentation of infants hospitalised with pertussis | Kahl ...

    African Journals Online (AJOL)

    Background. Despite the widespread use of pertussis vaccine, there has been a resurgence of pertussis cases in developed and developing countries. South Africa lacks data regarding clinical presentation and healthcare impact of pertussis. Objectives. To describe the clinical presentation and healthcare impact in ...

  15. Pertussis epidemic despite high levels of vaccination coverage with acellular pertussis vaccine.

    Science.gov (United States)

    Sala-Farré, Maria-Rosa; Arias-Varela, César; Recasens-Recasens, Assumpta; Simó-Sanahuja, Maria; Muñoz-Almagro, Carmen; Pérez-Jové, Josefa

    2015-01-01

    We describe the pertussis epidemic, based only on confirmed whooping cough cases. We have analyzed data on the diagnosis, epidemiology and vaccine history in order to understand the factors that might explain the trends of the disease. A descriptive study of the confirmed pertussis cases reported during 2011 in the Vallès region (population 1,283,000). Laboratory criteria for confirmed pertussis cases include isolation of Bordetella pertussis from a clinical specimen or detection of B. pertussis by PCR in nasopharyngeal swabs. A total of 421 pertussis confirmed cases were reported, which was the highest incidence reported in the last decade (33 cases/100,000 people/year in 2011). The highest incidence rate was among infants less than 1 year old (448/100,000), followed by children 5-9 years old (154/100,000). Pertussis cases aged 2 months-1 year were 90% vaccinated following the current DTaP schedule for their age group in Catalonia, and cases of 5-9 years were 87% fully vaccinated with 5 doses of DTaP vaccine. There were no deaths, although 8% of cases were hospitalized. Pertussis was more severe in infants, 30% required hospitalization despite having received the vaccine doses corresponding to their age. Children of 5-9 years were most often identified as primary cases in households or school clusters. Despite high levels of vaccination coverage, pertussis circulation cannot be controlled at all. The results question the efficacy of the present immunization programmes. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Determinants of responsiveness to botulinum toxin, casting, and bracing in the treatment of spastic equinus in children with cerebral palsy.

    Science.gov (United States)

    Yap, Rita; Majnemer, Annette; Benaroch, Thierry; Cantin, Marie-Andree

    2010-02-01

    The objective was to determine whether specific intrinsic (age, pattern of cerebral palsy [CP], child's motivation) and extrinsic (number of treatments, parenting stress) characteristics were associated with responsiveness to botulinum toxin A (BoNT-A) injections in children with CP 3 months after injection into the gastrocnemius muscle. Children with hemiplegia or diplegia recruited from a BoNT-A programme were evaluated before and 3 months following injection of BoNT-A into the gastrocnemius. Outcome measures included muscle tone, range of motion, gait pattern, level of ambulation, gross motor function, and functional independence. Determinants of responsiveness to BoNT-A considered were age, number of treatments, distribution of CP, parenting stress, and motivation. Thirty-one children were recruited (17 males, 14 females)--22 with hemiplegia and nine with diplegia. Twenty-eight were classified at Gross Motor Function Classification System (GMFCS) level I and three at level III. The mean age was 6 years 4 months (SD 2y 11mo). Younger age (p=0.015) and fewer number (p=0.024) of BoNT-A treatments were associated with greater change in gross motor function. Child's motivation and parenting stress were significantly associated with improvements in muscle tone (p=0.006-0.017), passive range of motion (p=0.008-0.033), gait pattern (p=0.005-0.042), level of ambulation (p=0.001-0.043), and functional independence (p=0.004-0.027). The results indicate that child, family, and treatment characteristics influence the degree of responsiveness to BoNT-A treatment. The contribution of contextual factors (personal and environmental) on responsiveness may be underappreciated in children with CP.

  17. Consensus Recommendations for Treatment Strategies in Indians Using Botulinum Toxin and Hyaluronic Acid Fillers

    Directory of Open Access Journals (Sweden)

    Krishan Mohan Kapoor, MCh, DNB

    2017-12-01

    Conclusions:. These recommendations give physicians treating Indians worldwide a better understanding of their unique facial characteristics and provide treatment strategies to achieve optimal aesthetic outcomes.

  18. Membrane Restructuring by Bordetella pertussis Adenylate Cyclase Toxin, a Member of the RTX Toxin Family

    Czech Academy of Sciences Publication Activity Database

    Martín, C.; Requero, M. A.; Mašín, Jiří; Konopásek, Ivo; Goni, F. M.; Šebo, Peter; Ostolaza, H.

    2004-01-01

    Roč. 186, č. 12 (2004), s. 3760-3765 ISSN 0021-9193 R&D Projects: GA AV ČR IAA5020907 Grant - others:GA European Union contract(XX) QLK2-1999-0.0556 Keywords : atc * lipid Subject RIV: EE - Microbiology, Virology Impact factor: 4.146, year: 2004

  19. Neurologic manifestations of diphtheria and pertussis.

    Science.gov (United States)

    Sanghi, Viraj

    2014-01-01

    Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

  20. Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO cell assay*

    Science.gov (United States)

    DALBY, TINE; SØRENSEN, CHARLOTTE; PETERSEN, JESPER WESTPHAL; KROGFELT, KAREN ANGELIKI

    2010-01-01

    Dalby T, Sørensen C, Petersen JW, Krogfelt KA. Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO cell assay. APMIS 2010; 118: 968–72. Two types of serological assays are commonly used for the assessment of pertussis vaccine-induced antibodies; the Chinese hamster ovary cell (CHO cell) assay and the immunoglobulin G (IgG) anti pertussis toxin (PT) enzyme-linked immunosorbent assay (IgG anti-PT ELISA). Recently, both the techniques have been modified to improve performance with sera with interfering activity (CHO cell assay) or with heat-treated sera (IgG anti-PT ELISA). These two improved techniques were compared by the analysis of 100 individual serum samples from a previous clinical trial and 213 sera from a longitudinal serum collection from 20 Danish adults recently vaccinated with the Danish acellular pertussis vaccine. The comparison showed a significant linear correlation between the results of the two assays with a p-value of ELISA can be used as a replacement for the often troublesome and time-consuming CHO cell assay for the measurement of vaccine-induced human antibodies to PT. PMID:21091778

  1. Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy

    Science.gov (United States)

    Vaughan, Kerrie; Seymour, Emily; Peters, Bjoern; Sette, Alessandro

    2016-01-01

    The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. The Immune Epitope Database (IEDB) is a repository of immune epitope data from the published literature and includes T cell and antibody epitopes for human pathogens. The IEDB conducted a review of the epitope literature, which revealed 300 Bordetella pertussis-related epitopes from 39 references. Epitope data are currently available for six virulence factors of B. pertussis: pertussis toxin, pertactin, fimbrial 2, fimbrial 3, adenylate cyclase and filamentous hemagglutinin. The majority of epitopes were defined for antibody reactivity; fewer T cell determinants were reported. Analysis of available protective correlates data revealed a number of candidate epitopes; however few are defined in humans and few have been shown to be protective. Moreover, there are a limited number of studies defining epitopes from natural infection versus whole cell or acellular/subunit vaccines. The relationship between epitope location and structural features, as well as antigenic drift (SNP analysis) was also investigated. We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level. PMID:24530743

  2. Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

    Science.gov (United States)

    Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

    2017-05-04

    Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

  3. Bordetella pertussis diagnosed by polymerase chain reaction

    DEFF Research Database (Denmark)

    Birkebaek, N H; Heron, I; Skjødt, K

    1994-01-01

    The object of this work was to test the polymerase chain reaction (PCR) for demonstration of Bordetella pertussis (BP) in nasopharyngeal secretions. The method was applied to patients with recently diagnosed pertussis, as verified by BP culture. In order to test the sensitivity and specificity...... in 25 patients in whose nasopharyngeal secretions BP had been demonstrated after 4-7 days of culture. The detection limit of PCR in aqueous solution was 1-2 BP bacteria per reaction tube. PCR was 100% specific for BP, showing no response with other Bordetella species or other bacteria known to colonize...

  4. Practical Aspects of Botulinum Toxin-A Treatment in Patients With Overactive Bladder Syndrome

    Directory of Open Access Journals (Sweden)

    Chun-Hou Liao

    2015-12-01

    Full Text Available Intravesical onabotulinumtoxinA (BoNT-A injection is an effective treatment for overactive bladder syndrome (OAB that is refractory to antimuscarinics. An injectable dose of 100 U has been suggested to achieve the optimal balance of benefit and safety in patients with OAB. BoNT-A (total volume of 10 mL was administered as evenly distributed intradetrusor injections (5 U across 20 sites approximately 1 cm apart (0.5 mL per site using a flexible or rigid cystoscope. Treatment with BoNT-A was generally well tolerated by most patients, and most treatment-related adverse events were localized to the urinary tract. The prevalence of OAB increases with age, and elderly patients are more vulnerable to complications. The short-term efficacy of intravesical BoNT-A injection for refractory OAB with no treatment-related complications in the elderly population has been documented. Frail elderly patients can experience the same treatment results, such as significantly improved urgent urinary incontinence and quality of life, as young and nonfrail elderly patients with 100-U BoNT-A injections. However, increased risk of larger postvoid residual (PVR urine and lower long-term success rates were noted in frail elderly patients; around 11% had acute urinary retention, while 60% had PVR urine volume >150 mL after treatment. In addition, intravesical injection of BoNT-A effectively decreased urgency symptoms in elderly patients with OAB and central nervous system lesions. The adverse effects were acceptable, while the long-term effects were comparable to those in patients with OAB without central nervous system lesions. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization in this vulnerable population requires careful evaluation before treatment with intravesical BoNT-A. In conclusion, the current findings indicate that intravesical BoNT-A is an effective and safe treatment for OAB in elderly patients.

  5. Incidental Treatment of a Subclinical Chronic Tension-Type Headache by Cosmetic Use of Botulinum Toxin A: A Case Report

    Directory of Open Access Journals (Sweden)

    Iselin Saltvig

    2017-11-01

    Full Text Available Background: Headache is a common disorder of the nervous system; chronic headache in particular may affect quality of life negatively. The pathophysiology is multifactorial and not completely elucidated. Studies have demonstrated the beneficial effects of botulinum toxin A on chronic migraine headaches, but failed to show the same effect on chronic tension-type headaches. Methods: We present the case of a 32-year-old woman who after receiving cosmetic injections with botulinum toxin A for fine lines of the forehead experienced relief of subclinical tension-type headaches. Conclusions: Although the effect of botulinum toxin A on chronic tension-type headaches is limited, several studies demonstrate its pain-modulating effects, and as such it is worth paying attention to this potential beneficial effect when performing cosmetic injections with botulinum toxin A.

  6. The effect and complication of botulinum toxin type a injection with serial casting for the treatment of spastic equinus foot.

    Science.gov (United States)

    Lee, Sook Joung; Sung, In Young; Jang, Dae Hyun; Yi, Jin Hwa; Lee, Jin Ho; Ryu, Ju Seok

    2011-06-01

    To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot. Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed weekly for 3 times. Spasticity of the ankle joint was evaluated using the modified Ashworth scale (MAS), and the modified Tardieu scale (MTS). Gait pattern was measured using the physician's rating scale (PRS). The degree of ankle dorsiflexion and the MAS improved significantly until 12 weeks following the BTX-A injection in the serial casting group (pcasting. Our study demonstrated that the effect of BTX-A injection with serial casting was superior and lasted longer than the effect of BTX-A injection only in patients with spastic equinus foot. We therefore recommend BTX-A injection with serial casting for the treatment of equinus foot. However, physicians must also consider the possible complications associated with serial casting.

  7. A Review of Thoracic Outlet Syndrome and the Possible Role of Botulinum Toxin in the Treatment of This Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew Travlos

    2012-11-01

    Full Text Available The objective of this paper is to discuss the classification, diagnosis, pathophysiology and management of Thoracic outlet syndrome (TOS. Thoracic outlet syndrome (TOS is a complex entity that is characterized by different neurovascular signs and symptoms involving the upper limb. TOS is defined as upper extremity symptoms due to compression of the neurovascular bundle in the area of the neck just above the first rib. Compression is thought to occur at one or more of the three anatomical compartments: the interscalene triangle, the costoclavicular space and the retropectoralis minor spaces. The clinical presentation can include both neurogenic and vascular symptoms. TOS can be difficult to diagnose because there is no standardized objective test that can be used and the clinician must rely on history and several positive findings on physical exam. The medial antebrachial cutaneous nerve conduction may be a sensitive way to detect pathology in the lower trunks of the brachial plexus which is promising for future research. Treatment options continue to be conservative and surgical. However, for those who have failed physical therapy there is research to suggest that botulinum toxin may help with symptom relief. However, given that there has been conflicting evidence, further research is required using randomized controlled trials.

  8. High heterogeneity in methods used for the laboratory confirmation of pertussis diagnosis among European countries, 2010: integration of epidemiological and laboratory surveillance must include standardisation of methodologies and quality assurance.

    Science.gov (United States)

    He, Q; Barkoff, A M; Mertsola, J; Glismann, S; Bacci, S

    2012-08-09

    Despite extensive childhood immunisation, pertussis remains one of the world’s leading causes of vaccine preventable deaths. The current methods used for laboratory diagnosis of pertussis include bacterial culture, polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) serology. We conducted a questionnaire survey to identify variations in the laboratory methods and protocols used among participating countries included in the European surveillance network for vaccine-preventable diseases(EUVAC.NET). In February 2010, we performed the survey using a web-based questionnaire and sent it to the country experts of 25 European Union countries,and two European Economic Area (EEA) countries,Norway and Iceland. The questionnaire consisted of 37 questions which covered both general information on surveillance methods and detailed laboratory methods used. A descriptive analysis was performed.Questionnaires were answered by all 27 contacted countries. Nineteen countries had pertussis reference laboratories at the national level; their functions varied from performing diagnosis to providing technical advice for routine microbiology laboratories. Culture,PCR and serology were used in 17, 18 and 20 countries,respectively. For PCR, nine laboratories used insertion sequence IS481 as the target gene, which is present in multiple copies in the Bordetella pertussis genome and thus has a greater sensitivity over single copy targets, but has been proved not to be specific for B.pertussis. Antibodies directed against pertussis toxin(PT) are specific for B. pertussis infections. For ELISA serology, only 13 countries’ laboratories used purified PT as coating antigen and 10 included World Health Organization (WHO) or Food and Drug Administration (FDA) reference sera in their tests. This present survey shows that methods used for laboratory confirmation of pertussis differ widely among European countries and that there is a great heterogeneity of the reference

  9. The potential role of Clostridium botulinum toxin in the treatment of equine laminitis

    NARCIS (Netherlands)

    Hardeman, L C

    2016-01-01

    Laminitis is a severe and painful disease in the horse that may lead to loosening of the attachment of the distal phalanx to the horny hoof capsule. Although a large variety of treatment options has come and gone since the first descriptions of laminitis, there is certainly a thus far unmet need for

  10. Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

    Science.gov (United States)

    Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

    2017-01-01

    Abstract Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection. PMID:28535276

  11. Detection of Bordetella pertussis using a PCR test in infants younger than one year old hospitalized with whooping cough in five Peruvian hospitals.

    Science.gov (United States)

    Castillo, María Esther; Bada, Carlos; Del Aguila, Olguita; Petrozzi-Helasvuo, Verónica; Casabona-Ore, Verónica; Reyes, Isabel; Del Valle-Mendoza, Juana

    2015-12-01

    To report the incidence, epidemiology, and clinical features of Bordetella pertussis in Peruvian infants under 1 year old. A prospective cross-sectional study was conducted in five hospitals in Peru from January 2010 to July 2012. A total of 392 infants under 1 year old were admitted with a clinical diagnosis of whooping cough and tested for B. pertussis by PCR. The pertussis toxin and IS481 genes were detected in 39.54% (155/392) of the cases. Infants aged less than 3 months were the most affected, with a prevalence of 73.55% (114/155). The most common household contact was the mother, identified in 20% (31/155) of cases. Paroxysm of coughing (89.03%, 138/155), cyanosis (68.39%, 106/155), respiratory distress (67.09%, 104/155), and breastfeeding difficulties (39.35%, 61/155) were the most frequent symptoms reported. An increase in pertussis cases has been reported in recent years in Peru, despite national immunization efforts. Surveillance with PCR for B. pertussis is essential, especially in infants less than 1 year old, in whom a higher rate of disease-related complications and higher mortality have been reported. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. The efficiency of botulinum toxin type A for the treatment of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

    Science.gov (United States)

    Pihut, Malgorzata; Ferendiuk, Ewa; Szewczyk, Michal; Kasprzyk, Katarzyna; Wieckiewicz, Mieszko

    2016-01-01

    Temporomandibular joint dysfunction are often accompanied by symptoms of headache such as tension-type headache which is the most frequent spontaneous primary headache. Masseter muscle pain is commonly reported in this group. The purpose of the study was to assess the efficiency of intramuscular botulinum toxin type A injections for treating masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. This prospective outcome study consisted of 42 subjects of both genders aged 19-48 years diagnosed with masseter muscle pain related to temporomandibular joint dysfunction and tension-type headache. The subjects were treated by the intramuscular injection of 21 U (mice units) of botulinum toxin type A (Botox, Allergan) in the area of the greatest cross-section surface of both masseter bellies. Pain intensity was evaluated using visual analogue scale (VAS) and verbal numerical rating scale (VNRS) 1 week before the treatment and 24 weeks after the treatment. The obtained data were analyzed using the Wilcoxon matched pairs test (p ≤ 0,005). The results of this study showed a decrease in the number of referred pain episodes including a decrease in pain in the temporal region bilaterally, a reduction of analgesic drugs intake as well as a decrease in reported values of VAS and VNRS after injections (p = 0,000). The intramuscular botulinum toxin type A injections have been an efficient method of treatment for masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache.

  13. 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.

  14. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  15. Recognizing and Preventing Whooping Cough 2 (Pertussis)

    Centers for Disease Control (CDC) Podcasts

    2010-09-16

    This podcast encourages everyone to get vaccinated against whooping cough (pertussis), especially those who will have close contact with an infant.  Created: 9/16/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/16/2010.

  16. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... immunizations about immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids ... abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  17. 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.

  18. Complement evasion by Bordetella pertussis: implications for improving current vaccines.

    Science.gov (United States)

    Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

    2015-04-01

    Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

  19. Treatment of Atlantoaxial Rotatory Fixation With Botulinum Toxin Muscle Block and Manipulation

    Directory of Open Access Journals (Sweden)

    Chia-Hung Lin

    2010-04-01

    Full Text Available Slippage after reduction of atlantoaxial rotatory fixation (AARF is usually treated with repeated cervical traction and brace immobilization. To date, no data have been published on the management of muscle spasm during treatment. Here, we describe the case of a 7-year-old girl with AARF for 1 month who visited our hospital for treatment. During physical examination, spasm of the sternocleidomastoid muscle was noted. The patient was treated with manipulative reduction, and slippage after reduction was managed with botulinum spasticity block of the sternocleidomastoid and splenius capitis muscles, and repeated manipulation. Cervical orthosis immobilization with a rehabilitation program of isometric contract–relax exercise for the neck was conducted for 3 months. The subject had full recovery from AARF at 1-year follow-up. This report demonstrates that, in selected cases of slippage after reduction from AARF, conservative management with manipulation under anesthesia is a good method, and the muscle components may play a crucial role in AARF.

  20. Treatment of atlantoaxial rotatory fixation with botulinum toxin muscle block and manipulation.

    Science.gov (United States)

    Lin, Chia-Hung; Chen, Chun-Jung; Chen, Chuan-Mu; Liao, Su-Lan; Raung, Shue-Ling; Tsai, Sen-Wei

    2010-04-01

    Slippage after reduction of atlantoaxial rotatory fixation (AARF) is usually treated with repeated cervical traction and brace immobilization. To date, no data have been published on the management of muscle spasm during treatment. Here, we describe the case of a 7-year-old girl with AARF for 1 month who visited our hospital for treatment. During physical examination, spasm of the sternocleidomastoid muscle was noted. The patient was treated with manipulative reduction, and slippage after reduction was managed with botulinum spasticity block of the sternocleidomastoid and splenius capitis muscles, and repeated manipulation. Cervical orthosis immobilization with a rehabilitation program of isometric contract-relax exercise for the neck was conducted for 3 months. The subject had full recovery from AARF at 1-year follow-up. This report demonstrates that, in selected cases of slippage after reduction from AARF, conservative management with manipulation under anesthesia is a good method, and the muscle components may play a crucial role in AARF. Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  1. Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.

    Directory of Open Access Journals (Sweden)

    César Martín

    Full Text Available Bordetella pertussis, the bacterium that causes whooping cough, secretes an adenylate cyclase toxin (ACT that must be post-translationally palmitoylated in the bacterium cytosol to be active. The toxin targets phagocytes expressing the CD11b/CD18 integrin receptor. It delivers a catalytic adenylate cyclase domain into the target cell cytosol producing a rapid increase of intracellular cAMP concentration that suppresses bactericidal functions of the phagocyte. ACT also induces calcium fluxes into target cells. Biochemical, biophysical and cell biology approaches have been applied here to show evidence that ACT and integrin molecules, along with other raft components, are rapidly internalized by the macrophages in a toxin-induced calcium rise-dependent process. The toxin-triggered internalisation events occur through two different routes of entry, chlorpromazine-sensitive receptor-mediated endocytosis and clathrin-independent internalisation, maybe acting in parallel. ACT locates into raft-like domains, and is internalised, also in cells devoid of receptor. Altogether our results suggest that adenylate cyclase toxin, and maybe other homologous pathogenic toxins from the RTX (Repeats in Toxin family to which ACT belongs, may be endowed with an intrinsic capacity to, directly and efficiently, insert into raft-like domains, promoting there its multiple activities. One direct consequence of the integrin removal from the cell surface of the macrophages is the hampering of their adhesion ability, a fundamental property in the immune response of the leukocytes that could be instrumental in the pathogenesis of Bordetella pertussis.

  2. Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.

    Science.gov (United States)

    Martín, César; Uribe, Kepa B; Gómez-Bilbao, Geraxane; Ostolaza, Helena

    2011-02-23

    Bordetella pertussis, the bacterium that causes whooping cough, secretes an adenylate cyclase toxin (ACT) that must be post-translationally palmitoylated in the bacterium cytosol to be active. The toxin targets phagocytes expressing the CD11b/CD18 integrin receptor. It delivers a catalytic adenylate cyclase domain into the target cell cytosol producing a rapid increase of intracellular cAMP concentration that suppresses bactericidal functions of the phagocyte. ACT also induces calcium fluxes into target cells. Biochemical, biophysical and cell biology approaches have been applied here to show evidence that ACT and integrin molecules, along with other raft components, are rapidly internalized by the macrophages in a toxin-induced calcium rise-dependent process. The toxin-triggered internalisation events occur through two different routes of entry, chlorpromazine-sensitive receptor-mediated endocytosis and clathrin-independent internalisation, maybe acting in parallel. ACT locates into raft-like domains, and is internalised, also in cells devoid of receptor. Altogether our results suggest that adenylate cyclase toxin, and maybe other homologous pathogenic toxins from the RTX (Repeats in Toxin) family to which ACT belongs, may be endowed with an intrinsic capacity to, directly and efficiently, insert into raft-like domains, promoting there its multiple activities. One direct consequence of the integrin removal from the cell surface of the macrophages is the hampering of their adhesion ability, a fundamental property in the immune response of the leukocytes that could be instrumental in the pathogenesis of Bordetella pertussis.

  3. Pulsed-Field Gel Electrophoresis Analysis of Bordetella pertussis Isolates Circulating in Europe from 1998 to 2009

    Science.gov (United States)

    Advani, Abdolreza; Hallander, Hans O.; Dalby, Tine; Krogfelt, Karen Angeliki; Guiso, Nicole; Njamkepo, Elisabeth; von Könnig, Carl Heinz Wirsing; Riffelmann, Marion; Mooi, Frits R.; Sandven, Per; Lutyńska, Anna; Fry, Norman K.; Mertsola, Jussi

    2013-01-01

    Between 1998 and 2009, Bordetella pertussis clinical isolates were collected during three periods, i.e., 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), and 2007 to 2009 (n = 140), from nine countries with distinct vaccination programs, i.e., Denmark, Finland, France, Germany, The Netherlands, Norway, Poland, Sweden, and the United Kingdom. Pulsed-field gel electrophoresis (PFGE) analysis was performed according to standardized recommendations for epidemiological typing of B. pertussis. There were 81 different PFGE profiles, five of which (BpSR3, BpSR5, BpSR10, BpSR11, and BpSR12) were observed in 61% of the 396 isolates and shown to be predominant in almost all countries. The major profile, BpSR11, showed a decreasing trend from 25% to 30% in 1998 to 2005 to 13% in 2007 to 2009, and there were increases in BpSR3 and BpSR10 from 0% and 8% to 21% and 22%, respectively. One difference between these profiles is that BpSR11 contains isolates harboring the fim3-2 allele and BpSR3 and BpSR10 contain isolates harboring the fim3-1 allele. The total proportion of the five predominant profiles increased from 44% in 1998 to 2001 to 63% in 2004 to 2005 to 70% in 2007 to 2009. In conclusion, common PFGE profiles were identified in B. pertussis populations circulating in European countries with different vaccination programs and different vaccine coverages. These prevalent isolates contain the novel pertussis toxin promoter ptxP3 allele. However, there is evidence for diversifying selection between ptxP3 strains characterized by distinct PFGE profiles. This work shows that, even within a relatively short time span of 10 years, successful isolates which spread through Europe and cause large shifts in B. pertussis populations may emerge. PMID:23175253

  4. Features of treatment of cervical dystonia associated with head tremor with botulinum toxin type A drugs under electro myographic control

    Directory of Open Access Journals (Sweden)

    A. N. Korenko

    2016-01-01

    Full Text Available The study was aimed to evaluate the efficacy and safety of injections of botulinum toxin typeA (BTA in the neck muscles under electromyographic control and without it to reduce head tremor, muscle tone and dystonic postures, as well as pain in patients with cervical dystonia (CD. 49 patients with CD and dystonic head tremor who received injections of BTA were examined. 33 (67 % patients received Dysport in an average dose of 695 (627; 762 units, 15 (31 % patients received Xeomin in an average dose of 262 (227; 297 units and 1 (2 % patient received 300 units of Botox. 16 (33 % patients received injections under EMGcontrol. The level of symptoms of CD and tremor before and 4 weeks after the treatment were measured by the TWSTRS and Tsui scales. Evaluation of the treatment efficacy was carried out using the patientreported Clinical Global Improvement (CGI scale, and the presence or absence of head tremor after injection was also recorded. The TWSTRS score decreased from 39 (36, 42 to 24 (21, 26, the TZUI score decreased from 9.8 (9, 10 to 4.9 (4, 6 in 4 weeks after injection (p <0.001. The level of tremor measured by Tsui scale decreased from 2.1 (1.7, 2.4 and 0.7 points (0,5; 0,9 (p <0.001. In 24 (49 % cases, complete disappearance of tremor was noted in 4 weeks after injection. Complete regression of tremor was observed significantly more frequently in patients with torticollis who received injections with EMG-control in 10(71 % cases vs. 8(32 % without it (p <0.05. 28(57 % patients noted moderate or significant improvement on the CGI scale. Pain decreased from 5.4 (3.9, 6.9 points to 2.4 (1.3, 3.6 (p <0.001 according to section 3 of TWSTRS scale, pain completely regressed in 15 (52 % patients. BTA injections are highly effective and safe treatment of CD symptoms such as dystonic posture, pain and dystonic tremor. BTA injections in the neck muscles under EMGcontrol can improve outcome in patients with torticollis associated with

  5. [Cases of pertussis among healthcare workers in a maternity ward: management of a health alert].

    Science.gov (United States)

    Vanjak, D; Delaporte, M F; Bonmarin, I; Levardon, M; Fantin, B

    2006-03-01

    Pertussis is a highly contagious acute respiratory tract infection, with a poor prognosis in non-vaccinated new-borns. The authors had for aim to investigate an epidemic of 5 pertussis cases among health care workers (HCW) in our maternity ward with potential exposure of new-borns and to evaluate HCW compliance and experience gain. A retrospective study was made using a questionnaire with HCW on preventive measures taken (antibiotic prophylaxis with erythromycin and wearing a mask). Two hundred and thirty-eight patients were warned of a potential pertussis contamination. No nosocomial case was detected among patients or their new borns. Ten proved or probable cases were identified among 101 HCW having answered (N=101/210, 48%). Sixty percent of HCW people followed the antibiotic treatment and 85% wore a mask among whom 46% adequately. Non-compliance factors were mainly related to adverse effects (41%), delayed information (41%), and false vaccine protection (22%). Crisis communication was felt as unsatisfactory for 72% of HCW and recommendations not adapted for 39% of the staff. This survey points out the difficulty of managing a pertussis alert in a medical ward.

  6. Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

    Science.gov (United States)

    Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

    2017-08-24

    When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Tetanus–diphtheria–acellular pertussis vaccination for adults: an update

    Science.gov (United States)

    2017-01-01

    Although tetanus and diphtheria have become rare in developed countries, pertussis is still endemic in some developed countries. These are vaccine-preventable diseases and vaccination for adults is important to prevent the outbreak of disease. Strategies for tetanus, diphtheria, and pertussis vaccines vary from country to country. Each country needs to monitor consistently epidemiology of the diseases and changes vaccination policies accordingly. Recent studies showed that tetanus–diphtheria–acellular pertussis vaccine for adults is effective and safe to prevent pertussis disease in infants. However, vaccine coverage still remains low than expected and seroprevalence of protective antibodies levels for tetanus, diphtheria, and pertussis decline with aging. The importance of tetanus–diphtheria–acellular pertussis vaccine administration should be emphasized for the protection of young adult and elderly people also, not limited to children. PMID:28168170

  8. Incidence and reproduction numbers of pertussis: estimates from serological and social contact data in five European countries.

    Directory of Open Access Journals (Sweden)

    Mirjam Kretzschmar

    2010-06-01

    Full Text Available BACKGROUND: Despite large-scale vaccination programmes, pertussis has remained endemic in all European countries and has been on the rise in many countries in the last decade. One of the reasons that have been discussed for the failure of vaccination to eliminate the disease is continued circulation of the pathogen Bordetella pertussis by mostly asymptomatic and mild infections in adolescents and adults. To understand the impact of asymptomatic and undiagnosed infection on the transmission dynamics of pertussis we analysed serological data from five European countries in combination with information about social contact patterns from five of those countries to estimate incidence and reproduction numbers. METHODS AND FINDINGS: We compared two different methods for estimating incidence from individual data on IgG pertussis toxin (PT titres. One method combines the cross-sectional surveys of titres with longitudinal information about the distribution of amplitude and decay rate of titres in a back-calculation approach. The second method uses age-dependent contact matrices and cross-sectional surveys of IgG PT titres to estimate a next generation matrix for pertussis transmission among age groups. The next generation approach allows for computation of basic reproduction numbers for five European countries. Our main findings are that the seroincidence of infections as estimated with the first method in all countries lies between 1% and 6% per annum with a peak in the adolescent age groups and a second lower peak in young adults. The incidence of infections as estimated by the second method lies slightly lower with ranges between 1% and 4% per annum. There is a remarkably good agreement of the results obtained with the two methods. The basic reproduction numbers are similar across countries at around 5.5. CONCLUSIONS: Vaccination with currently used vaccines cannot prevent continued circulation and reinfection with pertussis, but has shifted the bulk

  9. Botulinum Toxin Type A as Preoperative Treatment for Immediately Loaded Dental Implants Placed in Fresh Extraction Sockets for Full-Arch Restoration of Patients With Bruxism.

    Science.gov (United States)

    Mijiritsky, Eitan; Mortellaro, Carmen; Rudberg, Omri; Fahn, Miri; Basegmez, Cansu; Levin, Liran

    2016-05-01

    The aim of the present report was to describe the use of Botulinum toxin type A as preoperative treatment for immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration of patients with bruxism. Patients with bruxism who were scheduled to receive immediately loaded full-arch implant supported fixed restorations were included in this retrospective clinical report. To reduce the occlusal forces applied in patients with bruxism, Botulinum toxin type A was introduced prior to the implant placement procedure. Patients were followed and implant survival as well as peri-implant bone level was assessed in each periodic follow-up visit. Adverse effects were also recorded. A control group with no use of Botulinum toxin was evaluated as well. A total of 26 patients (13 test and 13 control), with bruxism, aged 59.15 ± 11.43 years on average were included in this retrospective report and received immediately loaded dental implants placed in fresh extraction sockets for full-arch restoration. The test group treatment preceded by Botulinum toxin type A injection. Maxillary arches were supported by 8 to 10 implants while the mandibular arch was supported by 6 implants. All surgeries went uneventfully and no adverse effects were observed. The average follow-up time was 32.5 ± 10.4 months (range, 18-51). In the test group, no implant failures were recorded. One patient presented with 1 to 2 mm bone loss around 4 of the implants; the other implants presented with stable bone level. In the control group 1 patient lost 2 implants and another demonstrated 2 mm bone loss around 3 of the implants. The preoperative use of Botulinum toxin in patients with bruxism undergoing full-arch rehabilitation using immediately loaded dental implants placed in fresh extraction sockets seems to be a technique that deserves attention. Further long-term, large-scale randomized clinical trials will help to determine the additional benefit of this suggested

  10. The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

    Science.gov (United States)

    Bakheit, Abdel Magid

    2010-01-01

    Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

  11. Pertussis: herd immunity and vaccination coverage in St Lucia.

    Science.gov (United States)

    Cooper, E; Fitch, L

    1983-11-12

    In a single complete epidemic in St Lucia, an island too small to support constant clinical pertussis, the pertussis case rates in small communities (villages and small towns) with differing levels of vaccination coverage of young children were compared. The association between greater vaccination coverage and greater herd immunity was clear, despite the imperfect protection given to individuals. An analysis in terms of population dynamics is evidence against the theory that endemic subclinical pertussis maintains transmission in a highly vaccinated population. We suggest that with a homogeneous vaccination coverage of 80% of 2-year-old children pertussis might be eradicated from the island, and that this is a practicable experiment.

  12. Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh

    DEFF Research Database (Denmark)

    Zeitlyn, S; Rahman, A K; Nielsen, B H

    1992-01-01

    OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose...... of the vaccine and followed up six weeks later to ascertain compliance with having second dose. Factors associated with non-compliance were evaluated. SETTING: Dhaka treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 136 unimmunised children aged 6 weeks to 23...... of immunisation, and she was given clear instructions to bring the child back after four weeks for the second dose. MAIN OUTCOME MEASURE: Rate of non-compliance with advice to return child for second vaccination. RESULTS: 46 of 113 children (41%) received the second dose of the vaccine. Factors most closely...

  13. A型肉毒毒素治疗抽动障碍%Botulinum toxin A in treatment of tic disorder

    Institute of Scientific and Technical Information of China (English)

    王琳; 万新华; 李力波

    2010-01-01

    Objective To evaluate the efficacy of Chinese botulinum toxin A(CBTX-A)injection in the treatment of motor tics in patients with tic disorder.Methods Twenty-five patients(20 male,5 female)were treated with CBTX-A in the sites of their most problematic motor tics.Before treatment the data of Yale Global Tic Severityb Scale(YGTSS)was collected.All patients were assessed at least 3 times after 1 week,4 weeks and within 12-month period.At each visit the following data were collected:YGTSS,Jankovic clinical rating scale,time to response,duration of response,global impression of changes by patients,presence of premonitory sensory tic component and side effects.Results Total number of treatment sessions was 29.The mean response time was 5.0 days.The mean duration of response was 4.6 months.The mean peak effect response in Jankovic clinical rating scale was 3.4.Based on YGTSS,62.1% (18/29)was rated as marked improvement,34.5%(10/29)as moderate improvement and only 3.4% (1/29)as no effect.85.7%(18/21)patients had less premonitory sensation symptoms(mean benefit 72.4%(20%-100%)).Weakness in the site of injection and rash were the main side effect. Conclusion CBTX-A is an effective and safe treatment for motor tics associated with tic disorder.%目的 探讨A型肉毒毒素治疗抽动障碍患者运动性抽动症状的疗效.方法 25例抽动障碍患者(男性20例,女性5例)接受国产A型肉毒毒素注射,治疗主要针对患者最突出的运动性抽动的表现.治疗前进行耶鲁综合抽动严重程度量表(YGTSS)基线评分,治疗1、4周和1年内分别进行YGTSS和Jankovic评分,并记录疗效的潜伏期、持续时间、副作用、患者的主观感觉和感觉先兆的变化以及再次注射情况.结果 在25例患者总共29人次的治疗中,肉毒毒素疗效平均潜伏期5.0 d,平均总体疗效持续4.6个月,平均最佳疗效Jankovic评分3.4分,根据YGTSS减分率统计62.1%(18/29)明显有效,34.5%(10/29)好转,3.4%(1/29)无效.85

  14. Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

    Science.gov (United States)

    Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

    2013-12-01

    The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

  15. Addressing harmful algal blooms (HABs) impacts with ferrate(VI): Simultaneous removal of algal cells and toxins for drinking water treatment.

    Science.gov (United States)

    Deng, Yang; Wu, Meiyin; Zhang, Huiqin; Zheng, Lei; Acosta, Yaritza; Hsu, Tsung-Ta D

    2017-11-01

    Although ferrate(VI) has long been recognized as a multi-purpose treatment agent, previous investigations regarding ferrate(VI) for addressing harmful algal blooms (HABs) impacts in drinking water treatment only focused on a single HAB pollutant (e.g. algal cells or algal toxins). Moreover, the performance of ferrate(VI)-driven coagulation was poorly investigated in comparison with ferrate(VI) oxidation, though it has been widely acknowledged as a major ferrate(VI) treatment mechanism. We herein reported ferrate(VI) as an emerging agent for simultaneous and effective removal of algal cells and toxins in a simulated HAB-impacted water. Ferrate(VI)-driven oxidation enabled algal cell inactivation and toxin decomposition. Subsequently, Fe(III) from ferrate(VI) reduction initiated an in-situ coagulation for cell aggregation. Cell viability (initial 4.26 × 10 4 cells/mL at pH 5.5 and 5.16 × 10 4 cells/mL at pH 7.5) decreased to 0.0% at ≥ 7 mg/L Fe(VI) at pH 5.5 and 7.5, respectively. Cell density and turbidity were dramatically decreased at pH 5.5 once ferrate(VI) doses were beyond their respective threshold levels, which are defined as minimum effective iron doses (MEIDs). However, the particulate removal at pH 7.5 was poor, likely because the coagulation was principally driven by charge neutralization and a higher pH could not sufficiently lower the particle surface charge. Meanwhile, algal toxins (i.e., microcystins) of 3.98 μg/L could be substantially decomposed at either pH. And the greater degradation achieved at pH 5.5 was due to the higher reactivity of ferrate(VI) at the lower pH. This study represents the first step toward the ferrate(VI) application as a promising approach for addressing multiple HABs impacts for water treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Serological evaluation of Bordetella pertussis infection in adults with prolonged cough].

    Science.gov (United States)

    Sönmez, Cemile; Çöplü, Nilay; Gözalan, Ayşegül; Yılmaz, Ülkü; Bilekli, Selen; Demirci, Nilgün Yılmaz; Biber, Çiğdem; Erdoğan, Yurdanur; Esen, Berrin; Çöplü, Lütfi

    2016-07-01

    Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0

  17. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

    Science.gov (United States)

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

  18. Pertussis vaccination and whooping cough: and now what?

    Science.gov (United States)

    Guiso, Nicole

    2014-10-01

    Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or Bordetella parapertussis that are only known to infect humans. This severe and acute respiratory disease presents epidemic cycles and became a vaccine-preventable disease in the 1940s/1950s when developed countries introduced vaccination. The first type of vaccine developed against this disease was a whole-cell pertussis (wP) vaccine containing inactivated B. pertussis bacteria. Most developed countries produced their own vaccine and given the pediatric nature of the disease at the time of licensure, infants and toddlers were the primary targets and were thus massively vaccinated. The characterization of few virulence factors produced by B. pertussis enabled the development of second-generation pertussis vaccines called the acellular pertussis (aP) vaccines. These only contain 1-5 purified, detoxified B. pertussis proteins and were first introduced in Japan around 30 years ago. Australia, Europe and North America introduced aP vaccines approximately 15 years later, which replaced wP vaccines since then.

  19. Crucial role of antibodies to pertactin in Bordetella pertussis immunity

    NARCIS (Netherlands)

    Hellwig, SMM; Rodriguez, ME; Berbers, GAM; de Winkel, JGJV; Mooi, FR

    2003-01-01

    Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central

  20. Pertussis vaccinations in Dutch children: memory immune responses

    NARCIS (Netherlands)

    Hendrikx, L.H.

    2011-01-01

    Despite high pertussis vaccination coverage, pertussis is reemerging in the Netherlands since 1996. In attempt to improve protection against whooping cough, two major changes in the national immunization program have been made; the introduction of a preschool booster vaccination in children 4 years

  1. Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment

    Directory of Open Access Journals (Sweden)

    Meining A

    2002-08-01

    Full Text Available Abstract Background It has been suggested that intrasphincteric injection of botulinum toxin (BTX may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection. Methods Forty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients. Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX. The symptoms were assessed using a global symptom score (0–10, which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy. Results After BTX injection, there was a significant reduction in LOSP (before, 38.2 ± 11.3 mmHg; 1 week after, 20.5 ± 6.9 mmHg; 1 month after, 17.8 ± 6.8 mmHg; P Conclusions BTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

  2. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.

    NARCIS (Netherlands)

    Dorji, Dorji; Mooi, Frits; Yantorno, Osvaldo; Deora, Rajendar; Graham, Ross M; Mukkur, Trilochan K

    Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis.

  3. Epidemiology of whooping cough & typing of Bordetella pertussis.

    Science.gov (United States)

    Hegerle, Nicolas; Guiso, Nicole

    2013-11-01

    Bordetella pertussis is a Gram-negative human-restricted bacterium that evolved from the broad-range mammalian pathogen, Bordetella bronchiseptica. It causes whooping cough or pertussis in humans, which is the most prevalent vaccine-preventable disease worldwide. The introduction of the pertussis whole-cell vaccination for young children, followed by the introduction of the pertussis acellular vaccination (along with booster vaccination) for older age groups, has affected the bacterial population and epidemiology of the disease. B. pertussis is relatively monomorphic worldwide, but nevertheless, different countries are facing different epidemiological evolutions of the disease. Although it is tempting to link vaccine-driven phenotypic and genotypic evolution of the bacterium to epidemiology, many other factors should be considered and surveillance needs to continue, in addition to studies investigating the impact of current clinical isolates on vaccine efficacy.

  4. Bordetella pertussis evolution in the (functional) genomics era

    Science.gov (United States)

    Belcher, Thomas; Preston, Andrew

    2015-01-01

    The incidence of whooping cough caused by Bordetella pertussis in many developed countries has risen dramatically in recent years. This has been linked to the use of an acellular pertussis vaccine. In addition, it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape. Genomics-based approaches have revolutionized the ability to resolve the fine structure of the global B. pertussis population and its evolution during the era of vaccination. Here, we discuss the current picture of B. pertussis evolution and diversity in the light of the current resurgence, highlight import questions raised by recent studies in this area and discuss the role that functional genomics can play in addressing current knowledge gaps. PMID:26297914

  5. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

    Directory of Open Access Journals (Sweden)

    Abu-lail Rasha

    2010-07-01

    Full Text Available Abstract Introduction Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences. Case presentation A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events. Conclusion On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.

  6. Different strictuctural requirements for adenylate cyclase toxin interactions with erythrocyte and liposome membranes

    Czech Academy of Sciences Publication Activity Database

    Mašín, Jiří; Konopásek, I.; Svobodová, J.; Šebo, Peter

    2004-01-01

    Roč. 1660, - (2004), s. 144-154 ISSN 0005-2736 R&D Projects: GA AV ČR IPP1050128; GA AV ČR IAA5020907 Grant - others:GA Howard Hughes Medical Institut(US) 55000334; GA(XE) QLK2-CT-1999-00556 Institutional research plan: CEZ:AV0Z5020903 Keywords : bordetella pertussis * adenylate cyclase toxin * membrane interaction Subject RIV: EE - Microbiology, Virology Impact factor: 3.441, year: 2004

  7. The effect of vitamin A supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model

    DEFF Research Database (Denmark)

    Jørgensen, Mathias Jul; Hein-Kristensen, Line; Hempel, Casper

    2011-01-01

    infectious diseases when given with the diphtheria-tetanus-pertussis (DTP) vaccine. The immunological effects of combining the 2 treatments are unknown. Methods: We studied the effect of treating C57BL/6 mice with VAS and DTP, 1 week prior to infection with Plasmodium berghei ANKA. The progression of disease...

  8. Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil.

    Science.gov (United States)

    Sartori, Ana Marli Christovam; de Soárez, Patrícia Coelho; Fernandes, Eder Gatti; Gryninger, Ligia Castellon Figueiredo; Viscondi, Juliana Yukari Kodaira; Novaes, Hillegonda Maria Dutilh

    2016-03-18

    Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing

  9. Evaluating the functional outcomes of ultrasound-guided botulinum toxin type A injections using the Euro-musculus approach for upper limb spasticity treatment in post-stroke patients; an observational study.

    Science.gov (United States)

    Buyukavci, Raikan; Akturk, Semra; Ersoy, Yüksel

    2018-02-07

    Ultrasound-guided botulinum toxin type A injection is an effective treatment for spasticity. Euro-musculus spasticity approach is a new method for administering injections to the correct point of the correct muscle. The clinical outcomes of this practical approach is not yet available in the literature. The purpose of this study was to evaluate the effects on spasticity and the functional outcomes of ultrasound guided botulinum toxin type A injections via the Euro-musculus spasticity approach to treat upper limb spasticity in post-stroke patients. An observational study. Inpatient post-stroke patients. Twenty five post-stroke patients with post-stroke upper limb spasticity were recruited. The ultrasound-guided botulinum toxin type A injections were administered into the spastic target muscles using the Euro-musculus spasticity approach, and all of the patients were enrolled in rehabilitation programmes after the injections. This research included the innervation zone and injection site figures and ultrasound images of each muscle in the upper limb. The degree of spasticity was assessed via the Modified Ashworth Scale and the upper limb motor function via the Fugl Meyer Upper Extremity Scale at the baseline and 4 and 12 weeks after the botulinum toxin type A injection. Significant decreases in the Modified Ashworth Scale scores of the upper limb flexor muscle tone measured 4 and 12 weeks after the botulinum toxin type A injection were found when compared to the baseline scores (pbotulinum toxin type A injection via the Euro- musculus spasticity approach is a practical and effective method for administering injections to the correct point of the correct muscle. Ultrasound-guided botulinum toxin type A injections combined with rehabilitation programmes decrease spasticity and improve the upper extremity motor functions in stroke patients. This new approach for ultrasound- guided botulinum toxin type A injection is very practical and effective method for upper

  10. 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.

  11. A Cough-Based Algorithm for Automatic Diagnosis of Pertussis

    Science.gov (United States)

    Pramono, Renard Xaviero Adhi; Imtiaz, Syed Anas; Rodriguez-Villegas, Esther

    2016-01-01

    Pertussis is a contagious respiratory disease which mainly affects young children and can be fatal if left untreated. The World Health Organization estimates 16 million pertussis cases annually worldwide resulting in over 200,000 deaths. It is prevalent mainly in developing countries where it is difficult to diagnose due to the lack of healthcare facilities and medical professionals. Hence, a low-cost, quick and easily accessible solution is needed to provide pertussis diagnosis in such areas to contain an outbreak. In this paper we present an algorithm for automated diagnosis of pertussis using audio signals by analyzing cough and whoop sounds. The algorithm consists of three main blocks to perform automatic cough detection, cough classification and whooping sound detection. Each of these extract relevant features from the audio signal and subsequently classify them using a logistic regression model. The output from these blocks is collated to provide a pertussis likelihood diagnosis. The performance of the proposed algorithm is evaluated using audio recordings from 38 patients. The algorithm is able to diagnose all pertussis successfully from all audio recordings without any false diagnosis. It can also automatically detect individual cough sounds with 92% accuracy and PPV of 97%. The low complexity of the proposed algorithm coupled with its high accuracy demonstrates that it can be readily deployed using smartphones and can be extremely useful for quick identification or early screening of pertussis and for infection outbreaks control. PMID:27583523

  12. Mouse lung adhesion assay for Bordetella pertussis

    Energy Technology Data Exchange (ETDEWEB)

    Burns, K A; Freer, J H [Department of Microbiology, Alexander Stone Building, Bearsden, Glasgow, Scotland

    1982-03-01

    The ability of Bordetella pertussis to adhere to cell surfaces has been demonstrated by adhesion to tissue culture cells and adhesion to chicken, hamster or rabbit trachea in organ culture. In this report a mouse lung assay for adhesion is described and the results obtained using two virulent strains of B. pertussis and their avirulent counterparts. These were a C modulation of one of the original virulent strains and a phase IV variant of the other virulent strain. Organisms were radiolabelled by adding 1 ..mu..Ci (37 K Bq) of (/sup 14/C)glutamic acid per 10 ml of culture medium before inoculation and incubation for 5 days. The lungs were washed by perfusion in situ with at least two volumes (1 ml) of sterile 1% (w/v) casamino acids. The percentage of the inoculated organisms retained in the lungs was determined, after removal of the lungs, by one of the following two methods: viable count or radioactive count. Results for both methods were expressed as the percentage of the inoculum retained in the lungs plus or minus one standard deviation.

  13. Mouse lung adhesion assay for Bordetella pertussis

    International Nuclear Information System (INIS)

    Burns, K.A.; Freer, J.H.

    1982-01-01

    The ability of Bordetella pertussis to adhere to cell surfaces has been demonstrated by adhesion to tissue culture cells and adhesion to chicken, hamster or rabbit trachea in organ culture. In this report a mouse lung assay for adhesion is described and the results obtained using two virulent strains of B. pertussis and their avirulent counterparts. These were a C modulation of one of the original virulent strains and a phase IV variant of the other virulent strain. Organisms were radiolabelled by adding 1 μCi (37 K Bq) of [ 14 C]glutamic acid per 10 ml of culture medium before inoculation and incubation for 5 days. The lungs were washed by perfusion in situ with at least two volumes (1 ml) of sterile 1% (w/v) casamino acids. The percentage of the inoculated organisms retained in the lungs was determined, after removal of the lungs, by one of the following two methods: viable count or radioactive count. Results for both methods were expressed as the percentage of the inoculum retained in the lungs plus or minus one standard deviation. (Auth.)

  14. Botulinum toxin type A-a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study

    DEFF Research Database (Denmark)

    Petersen, Christina Damsted; Giraldi, Annamaria; Lundvall, Lene

    2009-01-01

    to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline. MAIN OUTCOME MEASURES: Pain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured...... pain reduction (P placebo group...... in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months...

  15. Platelet cytosolic 44-kDa protein is a substrate of cholera toxin-induced ADP-ribosylation and is not recognized by antisera against the α subunit of the stimulatory guanine nucleotide-binding regulatory protein

    International Nuclear Information System (INIS)

    Molina Y Vedia, L.M.; Reep, B.R.; Lapetina, E.G.

    1988-01-01

    ADP-ribosylation induced by cholera toxin and pertussis toxin was studied in particulate and cytosolic fractions of human platelets. Platelets were disrupted by a cycle of freezing and thawing in the presence of a hyposmotic buffer containing protease inhibitors. In both fractions, the A subunit of cholera toxin ADP-ribosylates two proteins with molecular masses of 42 and 44 kDa, whereas pertussis toxin ADP-ribosylates a 41-kDa polypeptide. Two antisera against the α subunit of the stimulatory guanine nucleotide-binding regulatory protein recognize only the 42-kDa polypeptide. Cholera toxin-induced ADP-ribosylation of the 42- and 44-kDa proteins is reduced by pretreatment of platelets with iloprost, a prostacyclin analog. The 44-kDa protein, which is substrate of cholera toxin, could be extracted completely from the membrane and recovered in the cytosolic fraction when the cells were disrupted by Dounce homogenization and the pellet was extensively washed. A 44-kDa protein can also be labeled with 8-azidoguanosine 5'-[α- 32 P]triphosphate in the cytosol and membranes. These finding indicate that cholera and pertussis toxins produced covalent modifications of proteins present in particulate and cytosolic platelet fractions. Moreover, the 44-kDa protein might be an α subunit of a guanine nucleotide-binding regulatory protein that is not recognized by available antisera

  16. Multiplex PCR-based assay for detection of Bordetella pertussis in nasopharyngeal swab specimens.

    Science.gov (United States)

    Wadowsky, R M; Michaels, R H; Libert, T; Kingsley, L A; Ehrlich, G D

    1996-11-01

    A multiplex PCR-based assay was developed for the detection of Bordetella pertussis in nasopharyngeal swab specimens. The assay simultaneously amplified two separate DNA targets (153 and 203 bp) within a B. pertussis repetitive element and a 438-bp target within the beta-actin gene of human DNA (PCR amplification control). PCR products were detected by a sensitive and specific liquid hybridization gel retardation assay. A total of 496 paired nasopharyngeal swab specimens were tested by both the PCR-based assay and culture. Although 30 (6%) of the specimens inhibited the amplification of the beta-actin target, in all 29 specimens studied, the inhibition disappeared on repeat testing or was easily overcome with a 1:8 dilution or less of specimen digest. Of the 495 specimen pairs yielding a final evaluable result by the PCR-based assay, 19.0% were positive by the PCR-based assay, whereas 13.9% were positive by culture (P < 0.0001). After resolving the PCR-positive, culture-negative results by testing an additional aliquot from these specimens by the multiplex PCR-based assay, the PCR-based assay had a sensitivity and specificity of 98.9 and 99.7%, respectively, compared with values of 73.4 and 100%, respectively, for culture. In comparison with patients with culture-confirmed pertussis, those with PCR-positive, culture-negative results were older and more likely to have had prolonged cough, immunization with pertussis vaccine, or treatment with erythromycin. This multiplex PCR-based assay is substantially more sensitive than culture and identifies specimens that contain inhibitors of PCR.

  17. Estimated incidence of pertussis in people aged <50 years in the United States

    Science.gov (United States)

    Chen, Chi-Chang; Balderston McGuiness, Catherine; Krishnarajah, Girishanthy; Blanchette, Christopher M.; Wang, Yuanyuan; Sun, Kainan; Buck, Philip O.

    2016-01-01

    ABSTRACT The introduction of pertussis vaccination in the United States (US) in the 1940s has greatly reduced its burden. However, the incidence of pertussis is difficult to quantify, as many cases are not laboratory-confirmed or reported, particularly in adults. This study estimated pertussis incidence in a commercially insured US population aged pertussis or cough illness using International Classification of Diseases (ICD-9) codes, a commercial outpatient laboratory database for patients with a pertussis laboratory test, and the Centers for Disease Control influenza surveillance database. US national pertussis incidence was projected using 3 methods: (1) diagnosed pertussis, defined as a claim for pertussis (ICD-9 033.0, 033.9, 484.3) during 2008–2013; (2) based on proxy pertussis predictive logistic regression models; (3) using the fraction of cough illness (ICD-9 033.0, 033.9, 484.3, 786.2, 466.0, 466.1, 487.1) attributed to laboratory-confirmed pertussis, estimated by time series linear regression models. Method 1 gave a projected annual incidence of diagnosed pertussis of 9/100,000, which was highest in those aged pertussis of 649/100,000, approximately 58–93 times higher than method 1 depending on the year. These estimations, which are consistent with considerable underreporting of pertussis in people aged pertussis burden. PMID:27246119

  18. 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.

  19. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Ozturk, Kemal; de Rond, Lia G. H.; Veenhoven, Reinier H.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore

  20. 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...

  1. “Home of Younger Skin” (HOYS program: Defining the change in apparent skin age after facial treatment with botulinum toxin and dermal fillers

    Directory of Open Access Journals (Sweden)

    Goodman GJ

    2012-08-01

    Full Text Available Greg J Goodman, Stefania RobertsSouth Yarra, Melbourne, Victoria, AustraliaBackground: Objective and subjective scales estimating improvement in both clinical studies and clinical practice are becoming more mainstream. However, the use of a system to analyze improvement in aging with a multiplicity of treatments would be useful. The purpose of this study was to use a recently developed educative and patient self-assessment program (“Home of Younger Skin”, HOYS for assessment of the effect of facial treatment with neurotoxins and filling agents in terms of decreasing apparent age.Methods: Four patients underwent facial treatments with neurotoxins and dermal fillers by an experienced blinded physician and were assessed twice utilizing an age analysis program (HOYS, once before and then 6 weeks after completion of treatment.Results: The four patients showed an average reduction in apparent facial age of 7.5 years. The individual “regions” differed in their reductions. The upper face showed a decline of 13.5 years, the periorbital region 9.25 years, the mid face 4.5 years, and the lower face 12.25 years.Conclusion: Use of this previously validated self-assessment program may prove to be a useful measure of patient-reported improvement with treatment.Keywords: HOYS, rejuvenation, botulinum toxin, fillers, laser, aging

  2. Regulation of formyl peptide receptor binding to rabbit neutrophil plasma membranes. Use of monovalent cations, guanine nucleotides, and bacterial toxins to discriminate among different states of the receptor

    International Nuclear Information System (INIS)

    Feltner, D.E.; Marasco, W.A.

    1989-01-01

    The regulation by monovalent cations, guanine nucleotides, and bacterial toxins of [3H]FMLP binding to rabbit neutrophil plasma membranes was studied by using dissociation techniques to identify regulatory effects on separate receptor states. Under conditions of low receptor occupancy (1 nM [3H]FMLP) and in both Na+ and K+ buffers, dissociation is heterogenous, displaying two distinct, statistically significant off rates. [3H]FMLP binding was enhanced by substituting other monovalent cations for Na+. In particular, enhanced binding in the presence of K+ relative to Na+ was caused by additional binding to both rapidly and slowly dissociating receptors. Three receptor dissociation rates, two of which appear to correspond to the two affinity states detected in equilibrium binding studies, were defined by specific GTP and pertussis toxin (PT) treatments. Neither GTP, nor PT or cholera toxins (CT) had an effect on the rate of dissociation of [3H]FMLP from the rapidly dissociating form of the receptor. Both 100 microM GTP and PT treatments increased the percentage of rapidly dissociating receptors, correspondingly decreasing the percentage of slowly dissociating receptors. The observed changes in the rapidly and slowly dissociating receptors after GTP, PT, and CT treatments were caused by an absolute decrease in the amount of binding to the slowly dissociating receptors. However, complete inhibition of slowly dissociating receptor binding by GTP, PT, or both was never observed. Both GTP and PT treatments, but not CT treatment, increased by two-fold the rate of dissociation of 1 nM [3H]FMLP from the slowly dissociating form of the receptor, resulting in a third dissociation rate. Thus, slowly dissociating receptors comprise two different receptor states, a G protein-associated guanine nucleotide and PT-sensitive state and a guanine nucleotide-insensitive state

  3. Evaluation of the Specificity of BP3385 for Bordetella pertussis

    Science.gov (United States)

    BP3385 has been proposed as a diagnostic PCR target for discriminating between Bordetella pertussis and other Bordetella species that also infect humans. Our results demonstrate this gene is also present in some strains of Bordetella hinzii and Bordetella bronchiseptica....

  4. Pertussis outbreak in northwest Ireland, January - June 2010.

    LENUS (Irish Health Repository)

    Barret, A S

    2010-09-02

    We report a community pertussis outbreak that occurred in a small town located in the northwest of Ireland. Epidemiological investigations suggest that waning immunity and the absence of a booster dose during the second year of life could have contributed to the outbreak. The report also highlights the need to reinforce the surveillance of pertussis in Ireland and especially to improve the clinical and laboratory diagnosis of cases.

  5. Licensed pertussis vaccines in the United States. History and current state.

    Science.gov (United States)

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

  6. Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

    Science.gov (United States)

    Dai, Alper I; Demiryürek, Abdullah T

    2017-06-01

    The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P botulinum toxin type A in the serial casting group ( P botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

  7. Respiratory viral infections in infants with clinically suspected pertussis.

    Science.gov (United States)

    Ferronato, Angela E; Gilio, Alfredo E; Vieira, Sandra E

    2013-01-01

    to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. Implementation of pertussis immunization in health-care personnel.

    Science.gov (United States)

    Walther, Kathi; Burckhardt, Marie-Anne; Erb, Thomas; Heininger, Ulrich

    2015-04-21

    Infection with Bordetella pertussis is most severe in young infants who frequently acquire it from adults. Pertussis immunization in adults 25-29 years of age and all adults in close contact with infants vaccination campaign. Between April 2012 and March 2013 we provided information about the campaign to our staff through several channels and offered appointments for counseling and immunization. After checking indications and contraindications of responding health-care personnel (HCP), informed consent for tetanus-diphtheria-acellular pertussis component (Tdap) immunization was obtained. Specific adverse events (AE) were self-assessed by standardized diaries for 7 days. Statistical analyses were performed using a t-test and Mann-Whitney U-tests SPSS (V21). Of 852 HCP eligible for pertussis immunization, 427 (51%) responded. Of these, 72 (17%) had already received Tdap now, 38 (9%) were scheduled for vaccination and 12 (3%) declined. Diaries were returned by 272 (89%) of 304 vaccinees; 56 HCP reported ≥1 local AE, most frequently local swelling (8%), redness (2%), redness and swelling (7%), and fever (5=2%); no serious AE occurred. Comprehensive efforts were needed to achieve pertussis immunization coverage of ≥49% among all HCP in our institution. Good tolerability of the vaccine and continuous and individual information to HCP about the rationale and benefits of pertussis immunization contributed to this partial success, but increased efforts are needed to mobilize non-responding HCP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Evidence for an intact polysaccharide capsule in Bordetella pertussis.

    Science.gov (United States)

    Neo, YiLin; Li, Rui; Howe, Josephine; Hoo, Regina; Pant, Aakanksha; Ho, SiYing; Alonso, Sylvie

    2010-03-01

    Polysaccharide capsules contribute to the pathogenesis of many bacteria species by providing resistance against various defense mechanisms. The production of a capsule in Bordetella pertussis, the etiologic agent of whooping cough, has remained controversial; earlier studies reported this pathogen as a capsulated microorganism whereas the recent B. pertussis genome analysis revealed the presence of a truncated capsule locus. In this work, using transmission electron microscopy and immunostaining approaches, we provide a formal evidence for the presence of an intact microcapsule produced at the surface of both laboratory strain and clinical isolates of B. pertussis. In agreement with previous studies, we found that the capsule is optimally produced in avirulent phase. Unexpectedly, the presence of the capsule was also detected at the surface of virulent B. pertussis bacteria. Consistently, a substantial transcriptional activity of the capsule operon was detected in virulent phase, suggesting that the capsular polysaccharide may play a role during pertussis pathogenesis. In vitro assays indicated that the presence of the capsule does not affect B. pertussis adherence to mammalian cells and does not further protect the bacterium from phagocytosis, complement-mediated killing or antimicrobial peptide attack. Copyright 2009. Published by Elsevier SAS.

  10. Control of the Biofilms Formed by Curli- and Cellulose-Expressing Shiga Toxin-Producing Escherichia coli Using Treatments with Organic Acids and Commercial Sanitizers.

    Science.gov (United States)

    Park, Yoen Ju; Chen, Jinru

    2015-05-01

    Biofilms are a mixture of bacteria and extracellular products secreted by bacterial cells and are of great concern to the food industry because they offer physical, mechanical, and biological protection to bacterial cells. This study was conducted to quantify biofilms formed by different Shiga toxin-producing Escherichia coli (STEC) strains on polystyrene and stainless steel surfaces and to determine the effectiveness of sanitizing treatments in control of these biofilms. STEC producing various amounts of cellulose (n = 6) or curli (n = 6) were allowed to develop biofilms on polystyrene and stainless steel surfaces at 28°C for 7 days. The biofilms were treated with 2% acetic or lactic acid and manufacturer-recommended concentrations of acidic or alkaline sanitizers, and residual biofilms were quantified. Treatments with the acidic and alkaline sanitizers were more effective than those with the organic acids for removing the biofilms. Compared with their counterparts, cells expressing a greater amount of cellulose or curli formed more biofilm mass and had greater residual mass after sanitizing treatments on polystyrene than on stainless steel. Research suggests that the organic acids and sanitizers used in the present study differed in their ability to control biofilms. Bacterial surface components and cell contact surfaces can influence both biofilm formation and the efficacy of sanitizing treatments. These results provide additional information on control of biofilms formed by STEC.

  11. Changes in ocular higher-order aberrations following botulinum toxin treatment in patients with blepharospasm : BTX improves dry eye in patients with BEB.

    Science.gov (United States)

    Isshiki, Yoshihiko; Ishikawa, Hiroto; Mimura, Osamu

    2016-11-01

    To evaluate the effects of botulinum toxin type A (BTX-A) treatment in patients with benign essential blepharospasm (BEB) by monitoring the ocular surface and ocular higher-order aberrations (HOAs) before and after treatment. The present study reports a prospective case series of 38 patients (76 eyes, 11 men and 27 women; mean age 66.8 ± 9.8 years) with BEB who underwent BTX-A treatment at Kokura Memorial Hospital between 2013 and 2014. Patients were evaluated for ophthalmoscopic findings, Schirmer I test, tear film break-up time (t-BUT), HOAs, fluctuation index (FI), stability index (SI) using a wavefront aberrometer, 15 subjective symptoms using the Dry Eye-Related Quality of Life Score (DEQS), and complications before and after the treatment. After BTX-A treatment, the Schirmer I test score improved significantly from 5.9 ± 5.4 to 8.7 ± 6.1 mm and t-BUT recovered from 5.2 ± 1.7 to 7.3 ± 1.7 s. HOAs were classified into four patterns: stable (60.5 %), small fluctuation (14.5 %), sawtooth (17.1 %), and reverse sawtooth (7.9 %), and they significantly reduced after the treatment. Only FI (not SI) showed a marked reduction, and the DEQS significantly improved from 44.7 ± 21.6 to 37.6 ± 21.0 after the treatment (p treatment with a high potential to improve ocular surface disorders induced by BEB.

  12. Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects

    Directory of Open Access Journals (Sweden)

    Ana Paula Tedesco

    2014-08-01

    Full Text Available Objective:To report on the experience of injections of botulinum toxin A (BTA in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS level V.Methods:This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations, in which the basic aim was to look for adverse effects.Results:The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years. The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month.Conclusion:The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia.

  13. Two horizontal rectus eye muscle surgery combined with botulinum toxin for the treatment of very large angle esotropia. A pilot study.

    Science.gov (United States)

    Khan, Arif O

    2005-01-01

    To evaluate the effectiveness of a proposed new protocol for the primary treatment for very large angle esotropia: two muscle horizontal rectus muscle surgery with simultaneous botulinum toxin A injection in a small pilot study. Eight patients who had esotropia at near (ET') greater than 60 prism diopters (in actuality 70 to 100 prism diopters ET') underwent 2 muscle horizontal rectus surgery with simultaneous botulinum toxin A injection of the medial rectus intraoperatively. This was the only surgical procedure for all patients included in this report. Seven patients underwent bilateral medial rectus recession and bilateral injection, and one patient underwent a unilateral medial rectus recession / lateral rectus resection procedure with unilateral medial rectus injection. Postoperatively, 6 of the 8 patients demonstrated residual esotropia at near of less than 10 prism diopters and were considered "successful" by the conventional criteria of binocular alignment within 8 prism diopters of orthotropia. Two undercorrections occurred in patients with 100 and 85 prism diopters of preop ET' respectively. But 3 other patients with such large deviations had satisfactory results. All patients and families were satisfied with postoperative binocular alignment, so no further surgery was undertaken. The patient who underwent unilateral surgery had the least surgical effect and was the largest undercorrection, probably because only one medial rectus received a Botox injection. Considering only the bilateral cases, results were "successful" in 6 of 7 cases. Most patients suffered an extended period of Botox induced exotropia in the postop' period before recovery from the paresis. One patient had a transient, successfully treated, postoperative strabismic amblyopia while exotropic. Bilateral medial rectus recession with simultaneous botulinum injection is a safe and effective primary surgical procedure for very large angle esotropia. A more extensive study is indicated to

  14. 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

  15. A Belgian Serosurveillance/Seroprevalence Study of Diphtheria, Tetanus and Pertussis Using a Luminex xMAP Technology-Based Pentaplex

    Directory of Open Access Journals (Sweden)

    Raissa Nadège Caboré

    2016-05-01

    Full Text Available Serosurveillance and seroprevalence studies are an essential tool to monitor vaccine-preventable diseases. We have developed a magnetic bead-based pentaplex immunoassay (MIA for the simultaneous detection of IgG antibodies against diphtheria toxin (DT, tetanus toxin (TT, pertussis toxin (PT, filamentous hemagglutinin (FHA and pertactin (Prn. The in-house pentaplex MIA showed a good correlation with commercial ELISAs with correlation coefficients between 0.89 for PT and 0.98 for TT. Intra- and inter-assay variability was <10%. A total of 670 anonymized serum samples collected in 2012 in Belgian adults (ages 20–29.9 years were analyzed. Geometric mean concentrations (GMC were 0.2 (0.13–0.29 IU/mL for DT, 0.63 (0.45–0.82 IU/mL for TT, 3.9 (2.6–5.8 IU/mL for PT, 16.3 (11.7–22.7 IU/mL for FHA and 15.4 (10.1–23.6 IU/mL for Prn. Antibody concentrations were below the protective level of 0.1 IU/mL in 26.4% of the sera for DT and in 8.6% of the sera for TT. Anti-PT IgG concentrations indicative of recent pertussis infection (>125 IU/mL were detected in 1.2% of the subjects. High anti-PT antibodies were not correlated with high antibodies against any of the four other vaccine antigens. This pentaplex MIA will be used for a new large-scale Belgian serosurveillance/seroprevalence study of diphtheria, tetanus and pertussis.

  16. Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department

    Science.gov (United States)

    Zibners, Lara

    2017-02-01

    Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted.

  17. Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin.

    Science.gov (United States)

    Gonyar, Laura A; Gray, Mary C; Christianson, Gregory J; Mehrad, Borna; Hewlett, Erik L

    2017-06-01

    Pertussis (whooping cough), caused by Bordetella pertussis , is resurging in the United States and worldwide. Adenylate cyclase toxin (ACT) is a critical factor in establishing infection with B. pertussis and acts by specifically inhibiting the response of myeloid leukocytes to the pathogen. We report here that serum components, as discovered during growth in fetal bovine serum (FBS), elicit a robust increase in the amount of ACT, and ≥90% of this ACT is localized to the supernatant, unlike growth without FBS, in which ≥90% is associated with the bacterium. We have found that albumin, in the presence of physiological concentrations of calcium, acts specifically to enhance the amount of ACT and its localization to the supernatant. Respiratory secretions, which contain albumin, promote an increase in amount and localization of active ACT that is comparable to that elicited by serum and albumin. The response to albumin is not mediated through regulation of ACT at the transcriptional level or activation of the Bvg two-component system. As further illustration of the specificity of this phenomenon, serum collected from mice that lack albumin does not stimulate an increase in ACT. These data, demonstrating that albumin and calcium act synergistically in the host environment to increase production and release of ACT, strongly suggest that this phenomenon reflects a novel host-pathogen interaction that is central to infection with B. pertussis and other Bordetella species. Copyright © 2017 American Society for Microbiology.

  18. 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.

  19. Botulinum toxin therapy for treatment of spasticity in multiple sclerosis: review and recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders task force.

    Science.gov (United States)

    Dressler, Dirk; Bhidayasiri, Roongroj; Bohlega, Saeed; Chahidi, Abderrahmane; Chung, Tae Mo; Ebke, Markus; Jacinto, L Jorge; Kaji, Ryuji; Koçer, Serdar; Kanovsky, Petr; Micheli, Federico; Orlova, Olga; Paus, Sebastian; Pirtosek, Zvezdan; Relja, Maja; Rosales, Raymond L; Sagástegui-Rodríguez, José Alberto; Schoenle, Paul W; Shahidi, Gholam Ali; Timerbaeva, Sofia; Walter, Uwe; Saberi, Fereshte Adib

    2017-01-01

    Botulinum toxin (BT) therapy is an established treatment of spasticity due to stroke. For multiple sclerosis (MS) spasticity this is not the case. IAB-Interdisciplinary Working Group for Movement Disorders formed a task force to explore the use of BT therapy for treatment of MS spasticity. A formalised PubMed literature search produced 55 publications (3 randomised controlled trials, 3 interventional studies, 11 observational studies, 2 case studies, 35 reviews, 1 guideline) all unanimously favouring the use of BT therapy for MS spasticity. There is no reason to believe that BT should be less effective and safe in MS spasticity than it is in stroke spasticity. Recommendations include an update of the current prevalence of MS spasticity and its clinical features according to classifications used in movement disorders. Immunological data on MS patients already treated should be analysed with respect to frequencies of MS relapses and BT antibody formation. Registration authorities should expand registration of BT therapy for spasticity regardless of its aetiology. MS specialists should consider BT therapy for symptomatic treatment of spasticity.

  20. Botulinum toxin, a new treatment modality for chronic idiopathic constipation in children: long-term follow-up of a double-blind randomized trial.

    Science.gov (United States)

    Keshtgar, Alireza S; Ward, Harry C; Sanei, Ahmad; Clayden, Graham S

    2007-04-01

    Myectomy of the internal anal sphincter (IAS) has been performed on some children after failure of medical treatment to treat idiopathic constipation. The aim of this study was to compare botulinum toxin injection with myectomy of the IAS in the treatment of chronic idiopathic constipation and soiling in children. This was a double-blind randomized trial. Patients between 4 and 16 years old were included in the study if they had failed to respond to laxative treatment and anal dilatation for chronic idiopathic constipation. All study patients had anorectal manometry and anal endosonography under ketamine anesthesia. Outcome was measured using a validated symptom severity (SS) scoring system, with scores ranging from 0 to 65. Of 42 children, 21 were randomized to the botulinum group and 21 were randomized to the myectomy group. At the 3-month follow-up, the median preoperative SS score improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P 41) for the botulinum group and the myectomy group, respectively (P IAS for chronic idiopathic constipation and fecal incontinence in children.

  1. Keratoconus progression is not inhibited by reducing eyelid muscular force with botulinum toxin A treatment: a randomized trial

    Directory of Open Access Journals (Sweden)

    Adimara da Candelaria Renesto

    Full Text Available ABSTRACT Purpose: To evaluate whether reducing eyelid muscular force through the administration of botulinum toxin type A (BTX-A to the orbicularis oculi muscles of patients with keratoconus affected corneal parameters indicative of disease progression. Methods: In this prospective parallel randomized clinical trial, 40 eyes of 40 patients with keratoconus were randomized into equally sized control and BTX-A groups. Patients in the BTX-A group received subcutaneous BTX-A injections into the orbicularis muscle. The control group received no intervention. Palpebral fissure height, best spectacle-corrected visual acuity (BSCVA, and corneal topographic parameters were evaluated at baseline and at 3-, 6-, 12-, and 18-month follow-ups. Results: The mean ± standard deviation vertical palpebral fissure heights were 9.74 ± 1.87 mm and 9.45 ± 1.47 mm at baseline in the control and BTX-A groups, respectively, and 10.0 ± 1.49 mm and 9.62 ± 1.73 mm at 18 months, with no significant difference between the groups (p=0.337. BSCVA values were 0.63 ± 0.56 and 0.60 ± 0.27 at baseline in the control and BTX-A groups (p=0.643, and 0.52 ± 0.59 and 0.45 ± 0.26 at 18 months, again with no significant difference between the groups (p=0.452. In addition, there were no statistical differences between the groups at 18 months for the three keratometry topographic parameters: flattest (K1, steepest (K2, and mean (Km keratometry (p=0.562. Conclusion: BTX-A inhibition of eyelid force generation did not result in detectable changes in corneal parameters in keratoconic patients during 18 months of follow-up.

  2. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): ... vis-statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: ...

  3. DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

    Science.gov (United States)

    ... STATEMENT DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are ... www. immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by ...

  4. Tdap Vaccine (Tetanus, Diphtheria and Pertussis): What You Need to Know

    Science.gov (United States)

    ... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

  5. A retrospective study of acute pertussis in Hasan Sadikin Hospital–Indonesia

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2015-06-01

    Conclusions: Mostly patients were admitted on paroxysmal phase when no more active B. pertussis could be found from nasopharyngeal secret. A rigorous history taking particularly excessive cough, posttussive vomitting, and pertussis vaccination status need to be taken into account.

  6. Durability and Kinetics of Maternal Pertussis Antibodies in Infants of Mothers Immunized with Tdap During Pregnancy

    Science.gov (United States)

    Healy, C Mary; Rench, Marcia; Swaim, Laurie; Timmins, Audra; Vyas, Anuja; Ng, Nancy; Paulos, Simon; Park, So Hee; Jeyachandran, Amilia; Rajam, Gorisankar; Schiffer, Jarad; Baker, Carol J

    2017-01-01

    Abstract Background Infant protection against severe pertussis requires sufficient maternal pertussis antibodies until infant immunization begins. The kinetics of maternally-derived Tdap-induced antibodies in infants is poorly understood. Methods 34 healthy mother-infant pairs were followed prospectively from maternal Tdap immunization to infant age 6 weeks. Blood was collected from women pre-Tdap, 4 weeks post Tdap and at delivery, and from infants at birth, and age 3 and 6 weeks. IgG to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by luminex assay (IU/mL). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) for pertussis-specific IgG and half-life of IgG to PT were calculated. Results Mean maternal age was 31.1 years (range 22.7–39.7); 47% were white, 32% Hispanic and 21% Black. Tdap was administered at a mean gestation of 30.7 weeks (28–32.7). Infants had a mean gestation of 39.1 weeks (36–41.1) and birthweight of 3379g (2580–4584). GMCs (95%C.I.) for maternal pertussis-specific IgG increased significantly 4 weeks post-Tdap (4-fold higher in 59%, 41%, 29% and 44% for PT, FHA, FIM and PRN, respectively) and waned before delivery. Placental transfer was 135% for PT, 141% for FHA, 131% for FIM and 136% for PRN. Maternal antibodies in infants decayed quickly, but at age 6 weeks GMC of infant PT-specific IgG was 21.1IU/mL (14.7–30.2) and 91% had PT ≥ 10 IU/mL. Estimated half-life of PT-specific IgG in infants was 30.9 days. Time PT (IU/mL) FHA (IU/mL) FIM (IU/mL) PRN (IU/mL) Pre-Tdap 9.85 (6.71–14.45) 32.81 (21.79–49.42) 131.55 (81.98–211.15) 55.67 (35.75–86.68) Post-Tdap 46.8 (34.4–63.68) 116.82 (88.9–153.5) 440.35 (327.57–591.97) 233.02 (179.14–303.04) Maternal Delivery 40.78 (29.4–56.53) 104.81 (78.27–140.35) 384.5 (287.41–514.28) 204.41 (155.42–268.84) Infant Cord 55.12 (38.65–78.6) 147.81 (113.47–192.49) 505.36 (366.44–696.95) 278

  7. Seroepidemiology of pertussis among elementary school children in northern Taiwan.

    Science.gov (United States)

    Kuo, Ching-Chia; Huang, Yhu-Chering; Hsieh, Yu-Chia; Huang, Ya-Ling; Huang, Yu-Chiau; Hung, Yung-Tai

    2017-06-01

    Pertussis has been considered a vaccine-preventable "childhood disease", but a shift in age distribution has been reported worldwide. We conducted a seroepidemiological study in 2013 in Taiwan to elucidate the seroprevalence of pertussis among elementary school children. With a multilevel randomized method, which included 14 variables (4 population variables, 4 socio-educational variables, and 6 medical facilities' variables), the 29 executive districts of New Taipei City, Taiwan, were categorized into five strata. From each stratum, the number of school children as well as the number of elementary schools were proportionally selected. Enzyme immunoassay was applied for pertussis immunoglobulin-G measurement. A total of 936 children from 14 schools were recruited. Most participants (98.89%) received at least three doses of acellular diphtheria-tetanus-pertussis vaccine. The overall seropositive rate for pertussis was 33.97%. The seropositive rate was highest for students in Grade 1 (49.36%) and then declined with time, except for Grade 6 students. Students from Grade 1 to Grade 4 had a significant higher seropositive rate (37.18% vs. 27.56%, p = 0.002) than those from Grade 5 to Grade 6, but a lower geometric mean titer (18.71 NovaTec Unit/mL vs. 20.04 NovaTec Unit/mL, p = 0.20). For the class grades, geometric mean titers were positively correlated with seroprevalence (p Taiwan were seropositive for pertussis, a rate lower than expected. Seroprevalence declined with increasing class grades except for Grade 6. The current national immunization program may not provide adequate protection for children against pertussis. Copyright © 2015. Published by Elsevier B.V.

  8. Licensed pertussis vaccines in the United States: History and current state

    OpenAIRE

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that w...

  9. Community awareness and predictors of uptake of pertussis booster vaccine in South Australian adults.

    Science.gov (United States)

    Clarke, Michelle; Thomas, Natalie; Giles, Lynne; Marshall, Helen

    2015-12-16

    Pertussis is a highly virulent vaccine preventable disease that remains a global challenge. This study aimed to assess community knowledge of pertussis infection as well as awareness and uptake of adult pertussis booster vaccine. A cross-sectional survey was conducted of randomly selected households in South Australia by Computer Assisted Telephone Interviews in 2011. Survey data were weighted to the age, gender and geographical area profile of the population. From 3124 randomly sampled contactable households, 1967 interviews were conducted (participation rate 63%) with individuals aged 18-93 years, including 608 parents of children aged pertussis (whooping cough) and 18% reported that a household member had previously contracted whooping cough infection. Most respondents considered whooping cough to be highly contagious (73%) and severe for infants (89%). Over half (51%) of those surveyed were aware that family members commonly transmit pertussis to infants. Despite high knowledge, pertussis vaccine uptake was low, with only 10% of respondents reporting pertussis vaccination in the previous five years. Whilst 61% of respondents were aware of the availability of an adult pertussis booster vaccine, only 8% (n=154) reported their Family Physician had discussed it with them. If provided free, 77% agreed that they would be more likely to accept a booster pertussis vaccination. Independent predictors of recent pertussis vaccination included higher education, larger household size, perception of greater disease severity for infants and discussion with a Family Physician about pertussis vaccination. Whilst knowledge regarding transmission and severity of Bordetella pertussis was high, uptake of pertussis vaccination for adults is remarkably low amongst the South Australian community. Improved awareness regarding the availability of a booster pertussis vaccine through Family Physicians and/or provision of funded pertussis vaccination for adults has the potential to improve

  10. 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

  11. 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)

  12. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    Science.gov (United States)

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  13. Distonia laríngea: relato de caso e tratamento com toxina botulínica Laryngeal dystonia: case report and treatment with botulinum toxin

    Directory of Open Access Journals (Sweden)

    Victor José Barbosa Santos

    2006-06-01

    Full Text Available Distonia laríngea, ou disfonia espasmódica, é caracterizada por contrações involuntárias e inapropriadas da musculatura responsável pela fonação, sendo a do tipo adutora a mais comum. Caracteriza-se por quebras fonatórias, sendo seu diagnóstico confirmado por videolaringoestroboscopia. O tratamento de escolha é feito com a aplicação direta de toxina botulínica nos músculos responsáveis pelo movimento incoordenado. O objetivo desse trabalho é relatar o caso de uma paciente com diagnóstico de distonia laríngea do tipo adutora, tratada com toxina botulínica e discutir as vantagens e observações descritas na literatura a respeito desse tratamento.Laryngeal dystonia or spasmodic dysphonia is characterized by involuntary and innapropiate spasms of vocal muscles, having the adductor type as the most common one. It is chacterized by strain-strangled voice with pitch breaks. Diagnosis is made by means of videolaryngostroboscopic exam. The treatment of choice is done with botulinum toxin directly injected in the muscles responsible for the mismatched movement. The aim of this study is to report on an adductor- type dysphonia patient and to discuss the advantages and observations about this treatment reported in the literature.

  14. Persistence of pertussis immunity in children and adults : Influence of priming vaccination

    NARCIS (Netherlands)

    Lee, Saskia van der

    2018-01-01

    Pertussis, or whooping cough, is a highly contagious infection of the upper respiratory tract and may cause severe clinical disease, particularly in young unvaccinated infants. Despite a consistent high pertussis vaccination coverage, pertussis re-emerged in the late 1990s, with cyclic outbreaks

  15. Dynamic models for health economic assessments of pertussis vaccines : what goes around comes around ...

    NARCIS (Netherlands)

    Rozenbaum, M.H.; De Cao, E.; Westra, T.A.; Postma, M.J.

    2012-01-01

    Despite childhood vaccination programs, pertussis remains endemic. To reduce the burden of pertussis, various extended pertussis vaccination strategies have been suggested. The aim of this article is to evaluate dynamic models used to assess the cost-effectiveness of vaccination. In total, 16

  16. Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor.

    NARCIS (Netherlands)

    Hovingh, Elise Sofie; Mariman, Rob; Solans, Luis; Hijdra, Daniëlle; Hamstra, Hendrik-Jan; Jongerius, Ilse; van Gent, Marjolein; Mooi, Frits; Locht, Camille; Pinelli, Elena

    2018-01-01

    Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates.

  17. Bordetella pertussis: an underreported pathogen in pediatric respiratory infections, a prospective cohort study

    NARCIS (Netherlands)

    Brink, van den G.; Wishaupt, J.O.; Douma, J.C.; Hartwig, N.G.; Versteegh, F.G.A.

    2014-01-01

    Background: The incidence of pertussis has been increasing worldwide. In the Netherlands, the seroprevalence has risen higher than the reported cases, suggesting that laboratory tests for pertussis are considered infrequently and that even more pertussis cases are missed. The objective of our study

  18. Evidence for an intracellular niche for Bordetella pertussis in broncho-alveolar lavage cells of mice

    NARCIS (Netherlands)

    Hellwig, SMM; Hazenbos, WLW; van de Winkel, JGJ; Mooi, FR

    1999-01-01

    Bordetella pertussis can attach, invade and survive intracellularly in human macrophages in vitro. To study the significance of this bacterial feature in vivo, we analyzed the presence of viable bacteria in broncho-alveolar lavage (BAL) cells of mice infected with B, pertussis. We found B. pertussis

  19. The new health legacy: when pertussis becomes a heritage transmitted from mothers to infants.

    Science.gov (United States)

    Zouari, Asma; Smaoui, Hanen; Bousnina, Souad; Menif, Khaled; Ben Jaballah, Najla; Kechrid, Amel

    2011-10-01

    Despite high vaccination coverage rates, there has been a gradual increase in reported pertussis cases. Although whooping cough affects all ages, young infants continue to suffer the greatest pertussis disease burden. Adolescents and adults are the primary source of infection for young babies. In this paper, we report two cases involving the likely transmission of pertussis from mothers to infants in Tunisia.

  20. Supplemental treatment of rheumatoid arthritis with natural milk antibodies against enteromicrobes and their toxins: results of an open-labelled pilot study

    Directory of Open Access Journals (Sweden)

    Matsuno Takeo

    2011-01-01

    Full Text Available Abstract Background Environmental factors, particularly commensal bacteria in the gastrointestinal tract, may be involved in the pathogenesis of rheumatoid arthritis (RA. The aim of this study was to evaluate whether natural milk antibodies against a wide spectrum of pathogenic enteromicobes and their toxins modify the disease activity in RA. Methods Twenty patients with RA, whose disease activity was uncontrolled by authentic medications due to drug resistance, complications and/or risk factors were treated for 3 months with an oral administration of a whey protein concentrate (WPC containing high levels of natural milk antibodies. Eighteen background-matched RA patients, not supplemented with milk antibody adjunct, were used as controls. Results Statistically significant reduction of arthritis symptoms and improvement of intestinal disorders were observed only in the test group: effective in 8 (44%, possibly effective in 2 (12% and not effective in 8 (44% of 18 patients treated (2 patients withdrew based on an ad hoc "evaluation point", the sum of variables that are improved more than 20% among the 8 core variables used for the American College of Rheumatology (ACR response criteria. This disease modifying effect of the WPC disappeared upon cessation of treatment, but was reappeared upon reintroduction of it. Importantly, 7 of 8 non-responders carry DR15 haplotype (DRB1-1501 and 1502, whereas only 1 of 7 responders was DR15 positive (risk ratio: 6.1. Furthermore, the pre-clinical serum anti-LPS and anti-type II collagen antibody levels in the responders were higher or tended to be higher than those in the non-responders, suggesting that there are 2 sub-types of RA based on an interaction between gastrointestinal pathogens and MHC class II haplotypes. Conclusions The natural milk antibody preparation containing high levels antibodies against pathogenic enteromicrobes and their toxins seems to be effective in a certain RA subset, and deserves

  1. Nosocomial pertussis infection of infants: still a risk in 2009.

    Science.gov (United States)

    Paterson, Jennifer M; Sheppeard, Vicky

    2010-12-01

    The Sydney West Centre for Population Health investigated a confirmed pertussis infection in a health care worker on a maternity ward and identified pertussis infection in 4 neonates cared for by this case. This report describes the public health intervention to identify and prevent further cases. Of the 4 neonates, three were laboratory-confirmed cases and one was diagnosed on clinical grounds alone. All were cared for by the infected worker during only one shift and developed symptoms six to 16 days afterwards. No other possible source of infection was identified. This investigation highlights the need to maintain awareness, particularly amongst staff working with neonates, that pertussis infection can arise despite complete vaccination. Thus it is important to investigate new coughing illnesses and exclude symptomatic staff from contact with neonates until pertussis infection is excluded or effectively treated. The burden on the health system arising from a pertussis infection in a health care worker in a high-risk setting is also described with the hospitalisation of 4 infants, and prophylactic antibiotics given to 73 new mothers, infants and health care workers.

  2. Pertussis Serodiagnosis in Belgium from 1990 to 2009 ▿

    Science.gov (United States)

    Vincent, Muriel; Rodeghiero, Caroline; Eylenbosch, Romain; Mans, Yvan; Swalus-Steenhouwer, Jeannine; Piérard, Denis; Huygen, Kris; Vanhoof, Raymond

    2011-01-01

    Diagnosis of pertussis by culture and PCR is most sensitive when performed on nasopharyngeal specimens collected pertussis in Belgium from 1990 to 2009. In total, 13,163 patients were analyzed for Bordetella pertussis-specific antibodies by agglutination, complement fixation, immunofluorescence, and ELISA. The number of positive pertussis cases detected by serodiagnosis ranged between 50 and 150 annually. The mean age of positive cases increased from 9.9 years in 1990 to 33.9 years in 2009. Whereas from 1990 to 2003, children and young adolescents made up the majority of cases, from 2004 onwards, cases were detected in all age groups and the distribution became bimodal, with a first peak at the age of 10 to 20 years and a second at the age of 35 to 50 years. In contrast, patients diagnosed since 2001 by PCR and/or culture were mostly children younger than 1 year of age. Despite extensive childhood vaccination campaigns, whooping cough is still present in Belgium. Our findings confirm the potential role of adults in the continued transmission of pertussis and strongly warrant booster or cocoon vaccinations in older age groups. PMID:21346057

  3. Pertussis: A Review of Disease Epidemiology Worldwide and in Italy

    Directory of Open Access Journals (Sweden)

    Giovanni Gabutti

    2012-12-01

    Full Text Available Pertussis continues to be a relevant public-health issue. The high coverage rates achieved have decreased the spread of the pathogen, but the waning of immunity implies a relevant role of adolescents and adults in the infective dynamics as they may represent a significant source of infection for unvaccinated or incompletely immunized newborns. The passive surveillance system is affected by many limitations. The underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived, anyway, the unavailability of comprehensive data should not hamper the adoption of active prophylactic interventions aimed at preventing the impact of waning immunity on pertussis. To avoid an increase of the mean age of acquisition of the infection, a booster dose of low-antigen content combined vaccine should be adopted in adolescents and adults. A decreased risk of infection in newborns can be achieved with the cocoon strategy, although the debate on this aspect is still open and enhanced surveillance and further studies are needed to fine-tune the pertussis prevention strategy.

  4. A versatile, non genetically modified organism (GMO)-based strategy for controlling low-producer mutants in Bordetella pertussis cultures using antigenic modulation.

    Science.gov (United States)

    Goffin, Philippe; Slock, Thomas; Smessaert, Vincent; De Rop, Philippe; Dehottay, Philippe

    2015-08-01

    The uncontrolled presence of non-producer mutants negatively affects bioprocesses. In Bordetella pertussis cultures, avirulent mutants emerge spontaneously and accumulate. We characterized the dynamics of accumulation using high-throughput growth assays and competition experiments between virulent and avirulent (bvg(-) ) isolates. A fitness advantage of bvg(-) cells was identified as the main driver for bvg(-) accumulation under conditions of high virulence factor production. Conversely, under conditions that reduce their expression (antigenic modulation), bvg(-) takeover could be avoided. A control strategy was derived, which consists in applying modulating conditions whenever virulence factor production is not required. It has a wide range of applications, from routine laboratory operations to vaccine manufacturing, where pertussis toxin yields were increased 1.4-fold by performing early pre-culture steps in modulating conditions. Because it only requires subtle modifications of the culture medium and does not involve genetic modifications, this strategy is applicable to any B. pertussis isolate, and should facilitate regulatory acceptance of process changes for vaccine production. Strategies based on the same concept, could be derived for other industrially relevant micro-organisms. This study illustrates how a sound scientific understanding of physiological principles can be turned into a practical application for the bioprocess industry, in alignment with Quality by Design principles. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. [Optimization of the pertussis vaccine production process].

    Science.gov (United States)

    Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

    1995-01-01

    The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased.

  6. Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

    Science.gov (United States)

    Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

    2015-01-01

    Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

  7. 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.

  8. 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.

  9. Toxina botulínica no tratamento da dor Toxina botulínica en el tratamiento del dolor Botulinum toxin in pain treatment

    Directory of Open Access Journals (Sweden)

    Orlando Carlos Gomes Colhado

    2009-06-01

    indicaciones, todavía están en fase de comprobación con relación a su eficacia. El objetivo de este estudio fue revisar el historial, las propiedades farmacológicas y las aplicaciones clinicas de la TxB, cuando se usa en el tratamiento de dolores de diferentes etiologías. CONTENIDO: La TxB es el producto de la fermentación del Clostridium Botulinum, una bacteria anaerobia Gram-positiva. Comercialmente, las TxB existen bajo las formas A y B, agentes biológicos obtenidos laboratorialmente. La TxB, una neurotoxina que posee una alta afinidad por las sinapsis colinérgicas, ocasiona un bloqueo en la liberación de acetilcolina por el terminal nervioso, sin alterar la conducción neural de las señales eléctricas o la síntesis y el almacenaje de acetilcolina. Se ha comprobado que la TxB puede debilitar selectivamente la musculatura dolorosa, interrumpiendo el ciclo espasmo-dolor. Con relación a él, varias publicaciones han demostrado la eficacia y la seguridad de la TxB-A en el tratamiento de la cefalea tipo tensión, migraña, dolor lumbar crónico y dolor miofacial. CONCLUSIONES: La TxB-A es segura y se tolera muy bien en los desórdenes dolorosos crónicos, donde los regímenes de farmacoterapia pueden de hecho provocar efectos colaterales. Otra ventaja es la reducción del uso de analgésicos y el tiempo de acción de 3 a 4 meses por dosis. Sin embargo, investigaciones futuras serán necesarias para establecer la eficacia de la TxB-A en los desórdenes dolorosos crónicos y su exacto mecanismo en el alivio del dolor, como también su potencial en tratamientos multifactoriales.BACKGROOUND AND OBJECTIVES: 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

  10. PERTUSSIS IS COMING BACK? IMPROVEMENT OF FORGOTTEN CHILDHOOD INFECTION CONTROL

    Directory of Open Access Journals (Sweden)

    M. V. Fedoseenko

    2012-01-01

    Full Text Available Infection that more than 60 years ago was recognized one of the leading childhood diseases that caused infant mortality, is returning. Of course, with the introduction of vaccination against pertussis in the national programs, we rarely meet severe pertussis infection in our practice, considering that vaccinating children, we protect them. But why so far is this infectious disease remains a serious problem not only in Russia but throughout the world? Several global reasons contribute to the fact that until now vaccine-preventable diseases leads to a prolonged, exhausting cough in schoolchildren, deceiving the doctors with the correct diagnosis is still a real threat to infants. 

  11. [Whooping cough in an urban high school in Hungary. Conclusions of a local pertussis outbreak].

    Science.gov (United States)

    Schneider, Ferenc; Stánitz, Eva; Kalácska, Judit; Tompity, Tünde; Gábor, Beáta

    2009-08-16

    Although incidence of pertussis has been gradually decreased with the introduction of active immunization, total eradication is not possible. This has been shown by national and international data, as well. In the early 2000's, slow increase in incidence of pertussis was observed. To demonstrate the presence of Bordetella pertussis in the Hungarian population by presenting 17 cases of adolescent pertussis. Etiology of pertussis was confirmed by quantification of pertussis-antibodies in blood samples taken from permanently coughing patients in the firstly identified subject's vicinity which latter was explored by retrospective data collection. In the vicinity of the first identified patient epidemiologic research identified another 16 patients all of which were confirmed by serological tests. If permanent coughing is present, pertussis needs to be ruled out. Immunity against pertussis obtained by vaccination fades by the end of childhood. Bordetella pertussis circulates in the national population. A booster-vaccination against pertussis in the regular vaccination course for the 11-year old children is recommended. Pertussis in adolescents and in adults is mild and atypical, but in case of prolonged coughing it needs to be considered.

  12. High frequency of pertussis in older children and adolescents with prolonged cough in Turkey.

    Science.gov (United States)

    Aslan, Aslı; Kurugöl, Zafer; Aydemir, Şöhret; Gürsel, Derya; Koturoğlu, Güldane

    2016-01-01

    This study aimed to determine the frequency of B. pertussis infection among Turkish children with prolonged cough. Nasopharyngeal specimens were collected from 7-18 year old children, presenting with prolonged cough of two to four weeks' duration. Specimens were examined for B. pertussis by PCR. Of 101 children with prolonged cough, 20 (19.8%) had a positive PCR testing for B. pertussis. Children who were vaccinated ≥5 years previously had a 6.13-fold higher risk of PCR-confirmed pertussis than those who were vaccinated pertussis (paroxysmal cough, whooping and post-tussive vomiting) were seen in 30%, 15% and 25% of the patients with positive PCR, respectively; 55% of them had only a prolonged cough without any classic symptoms. Pertussis is common among Turkish children with prolonged cough, even after implementation of a fifth dose of pertussis vaccination and despite high vaccination coverage.

  13. 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.

  14. Acylation of lysine 983 is sufficient for toxin activity of Bordetella pertussis adenylate cyclase

    Czech Academy of Sciences Publication Activity Database

    Basar, T.; Havlíček, Vladimír; Bezoušková, Silvia; Hackett, M.; Šebo, Peter

    2001-01-01

    Roč. 276, č. 1 (2001), s. 348-354 ISSN 0021-9258 R&D Projects: GA ČR GA310/98/0432; GA ČR GV310/96/K102; GA AV ČR IAA5020907; GA MŠk ME 167; GA MŠk VS96149 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EE - Microbiology, Virology Impact factor: 7.258, year: 2001

  15. Inflammasome Activation by Adenylate Cyclase Toxin Directs Th17 Responses and Protection against Bordetella pertussis

    Czech Academy of Sciences Publication Activity Database

    Dunne, A.; Ross, P. J.; Pospíšilová, Eva; Mašín, Jiří; Meaney, A.; Sutton, C. E.; Iwakura, Y.; Tschopp, J.; Šebo, Peter; Mills, K. H. G.

    2010-01-01

    Roč. 187, č. 3 (2010), s. 1711-1719 ISSN 0022-1767 R&D Projects: GA ČR GA310/08/0447; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : ADAPTIVE IMMUNE-RESPONSES * IL-17-PRODUCING T-CELLS * HOST-DEFENSE Subject RIV: EC - Immunology Impact factor: 5.745, year: 2010

  16. Influence of pertussis toxin pretreatment on the development of L-NAME-induced hypertension

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Kuneš, Jaroslav; Vranková, S.; Jendeková, L.; Dobešová, Zdenka; Pintérová, Mária; Pecháňová, Olga

    2009-01-01

    Roč. 58, č. 5 (2009), s. 751-755 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0139; GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : sympathetic nervous system * nitric oxide * inhibitory G proteins Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  17. Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis.

    Science.gov (United States)

    Friedmacher, Florian; Puri, Prem

    2012-08-01

    Internal anal sphincter (IAS) achalasia is a clinical condition with presentation similar to Hirschsprung's disease, but with the presence of ganglion cells on rectal suction biopsy (RSB). The diagnosis is made by anorectal manometry (ARM), which demonstrates the absence of the rectosphincteric reflex on rectal balloon inflation. The recommended treatment of choice is posterior IAS myectomy. Recently, intrasphincteric botulinum toxin (Botox) injection has been effectively used for treatment of IAS achalasia. The aim of this meta-analysis was to compare the efficacy of posterior IAS myectomy with intrasphincteric Botox injection for treatment of IAS achalasia. A systematic literature search for relevant articles was conducted using the following databases: MEDLINE( ® ), EMBASE(®), ISI Web of Science(SM) and the Cochrane Library. A meta-analysis was performed with the studies where IAS achalasia was diagnosed based on the results of ARM and RSB. Odds ratio (OR) with 95 % confidence intervals were calculated. Sixteen prospective and retrospective studies, published from 1973 to 2009, were identified. A total of 395 patients with IAS achalasia were included in this meta-analysis. Fifty-eight percent of patients underwent IAS myectomy and 42 % Botox injection. Regular bowel movements were significantly more frequent after IAS myectomy (OR 0.53, [95 % CI 0.29-0.99]; p = 0.04). There was no significant difference in continued use of laxatives or rectal enemas (OR 0.92, [95 % CI 0.34-2.53], p = 0.89) and in overall complication rates between both procedures (OR 0.68, [95 % CI 0.38-1.21]; p = 0.19). Looking at specific complications, the rate of transient faecal incontinence was significantly higher after Botox injection (OR 0.07, [95 % CI 0.01-0.54]; p IAS myectomy (OR 0.56, [95 % CI 0.32-0.97]; p = 0.04 and OR 0.25, [95 % CI 0.15-0.41]; p IAS achalasia, posterior IAS myectomy appears to be a more effective treatment option compared to intrasphincteric

  18. 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 ...

  19. Immunogenicity and safety of an acellular pertussis, diphtheria ...

    African Journals Online (AJOL)

    Objective. To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens. Methods. A DTaP-IPV//PRP~T vaccine (Pentaxim™) was given at 6, 10 and 14 weeks of age to 212 ...

  20. Respiratory viral infections in infants with clinically suspected pertussis

    Directory of Open Access Journals (Sweden)

    Angela E. Ferronato

    2013-11-01

    Conclusion: the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP.

  1. Pertussis: clinical and bacteriological diagnosis of six cases

    Directory of Open Access Journals (Sweden)

    Arellano Penagos Mario

    2014-07-01

    Full Text Available ertussis is an endemic disease in our population. Every 3 to 4 years, pertussis has an epidemic pattern even in countries with good health conditions. Antipertussis vaccine first dose is adminis- tered at the age of 2 months; a second and third dose are given at 4 and 6 months of age. This vaccine has an 8 to 10 year protective effect, for which reason it is suggested that pregnant women in the third trimester should be vaccinated in order to prevent pertussis in newborns. It should also be administered to older people to avoid turning them into asymptomatic carriers. Clinic manifestations are easily identifiable due to respiratory symptoms, especially to the particular characteristics of the cough. The diagnosis is supported by the presence of leukocytosis (predominantly lymphocytes and by certain thoracic radiologic findings. The diagnosis is confirmed with a positive culture for Bordetella pertussis or with a polymerase chain reaction (PCR. In a non complicated clinic course macrolides are still the best therapeutic choice. Nonetheless clinic observation is highly recom- mended in order to avoid complications. Redefinition of vaccine programs against Bordetella pertussis in Mexican population is recommended and also to notify the presence of the disease to the corresponding health authorities.

  2. Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan

    Science.gov (United States)

    Miyaji, Yusuke; Otsuka, Nao; Arakawa, Yoshichika; Shibayama, Keigo; Kamachi, Kazunari

    2017-01-01

    Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014–2016 (8%) was significantly lower than the frequency in 2005–2007 (41%), 2008–2010 (35%), and 2011–2013 (25%). This reduction was closely associated with changes in genotypes. PMID:28322702

  3. Proteome analysis of Bordetella pertussis isolated from human macrophages

    Czech Academy of Sciences Publication Activity Database

    Lamberti, Y.; Cafiero, J.H.; Surmann, K.; Valdez, H.; Holubová, Jana; Večerek, Branislav; Šebo, Peter; Schmidt, F.; Völker, U.; Rodriguez, M.E.

    2016-01-01

    Roč. 136, MAY16 (2016), s. 55-67 ISSN 1874-3919 R&D Projects: GA MŠk(CZ) 7AMB14AR028 Institutional support: RVO:61388971 Keywords : Bordetella pertussis * Intracellular survival * Proteomics Subject RIV: EE - Microbiology, Virology Impact factor: 3.914, year: 2016

  4. Dynamics of Pertussis Transmission in the United States

    Science.gov (United States)

    Magpantay, F. M. G.; Rohani, P.

    2015-01-01

    Past patterns of infectious disease transmission set the stage on which modern epidemiologic dynamics are played out. Here, we present a comprehensive account of pertussis (whooping cough) transmission in the United States during the early vaccine era. We analyzed recently digitized weekly incidence records from Morbidity and Mortality Weekly Reports from 1938 to 1955, when the whole-cell pertussis vaccine was rolled out, and related them to contemporary patterns of transmission and resurgence documented in monthly incidence data from the National Notifiable Diseases Surveillance System. We found that, during the early vaccine era, pertussis epidemics in US states could be categorized as 1) annual, 2) initially annual and later multiennial, or 3) multiennial. States with predominantly annual cycles tended to have higher per capita birth rates, more household crowding, more children per family, and lower rates of school attendance than the states with multiennial cycles. Additionally, states that exhibited annual epidemics during 1938–1955 have had the highest recent (2001–2010) incidence, while those states that transitioned from annual cycles to multiennial cycles have had relatively low recent incidence. Our study provides an extensive picture of pertussis epidemiology in the United States dating back to the onset of vaccination, a back-story that could aid epidemiologists in understanding contemporary transmission patterns. PMID:26022662

  5. Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth / For ... child outweigh the potential risks. Caring for Your Child After DTaP Immunization Your child may have a ...

  6. Pertussis in children in Bloemfontein, South Africa: A 7-year ...

    African Journals Online (AJOL)

    is a notifiable disease in this country, data on the burden of disease before and after the ..... ≥20.0 × 109/L. A lymphocyte predominance was found in 52/86 .... do get pertussis and act as reservoirs for transmission to infants and children.

  7. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    International Nuclear Information System (INIS)

    May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan

    2004-01-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine

  8. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    Energy Technology Data Exchange (ETDEWEB)

    May, J.C. E-mail: may@cber.fda.gov; Rey, L. E-mail: louis.rey@bluewin.ch; Lee, C.-J.; Arciniega, Juan

    2004-10-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  9. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  10. 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.

  11. Acellular pertussis vaccines--a question of efficacy.

    Science.gov (United States)

    Olin, P

    1995-06-01

    Whole cell pertussis vaccine is considered to offer at least 80% protection against typical whooping cough. The quest for an equally effective but less reactogenic vaccine is now drawing to a close. During the forthcoming year a number of efficacy trials of acellular pertussis vaccines will be terminated. A variety of vaccines containing one, two, three or five purified pertussis antigens are being tested in Germany, Italy, Senegal and Sweden. About 30,000 infants have been enrolled in placebo-controlled studies and more than 100,000 in whole cell vaccine-controlled trials. The final plans for analysis of a Swedish placebo-controlled trial of whole cell and acellular vaccines is presented. Due to the unexpected high incidence of pertussis in Sweden during 1993-1994, relative risk comparisons between vaccines will be attempted in that trial, in addition to estimating absolute efficacy. A crucial issue is to what extent data may be compared between trials, given differences in design, vaccination schedules, and chosen endpoints. A primary case definition of laboratory-confirmed pertussis with at least 21 days of paroxysmal cough have been adopted in most trials. Pre-planned meta-analysis using this single endpoint will facilitate comparisons between vaccines. Serological correlates to protection in individuals will be sought in the ongoing placebo-controlled trials. The concept of a serological correlate valid for a vaccinated population but not necessarily for the vaccinated individual, as is the case with Hib vaccines, may turn out to be the only alternative to performing large efficacy trials in the future.

  12. The Diagnostic Value of ELISA Method for Pertussis in Children

    Directory of Open Access Journals (Sweden)

    O. P. Popova

    2016-01-01

    Full Text Available Because of low effectiveness of laboratory methods for diagnosing pertussis it is important to look for new ways of verification of this infection. The article presents the analysis of the diagnostic value of ELISA method, which involves the identification of antibodies of different isotypes (IgM, IgG, IgA to pertussis toxoid (PT and filamentous haemagglutinin (FHA. The study included 279 children: 114 were under 1 year of age, 165 — older than 1 year. The pertussis was confirmed in 74.3 ± 2.6% of patients by using ELISA method. A significant proportion of seronegative patients (46.1 ± 6.2 per cent was revealed in the group of patients under 1 year. The pattern of production of antibodies in unvaccinated children was different. It depended on the age of the children and timing of illness. A low proportion of diagnostically significant indicators of IgM-antibodies at 2—3 weeks of illness was typical for patients under 1 year of age (e.g. 6.7 ± 6.5% as compared to 20.0 ± 7.9% and 50.0 ± 15.3 — 1—3 and 4—6 years of age. The diagnosis of pertussis in children under 1 year of age was confirmed mainly by the detection of IgG, starting from the 4th week of the disease. In the examination of vaccinated children diagnostically significant levels of IgA and IgG were identified (even in the late stages of the disease. Thus, the results of the analysis show special significance of using ELISA method for the diagnosis of pertussis in vaccinated children.

  13. Botulinum toxin a in the treatment of chronic tension-type headache with cervical myofascial trigger points: a randomized, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Harden, R Norman; Cottrill, Jerod; Gagnon, Christine M; Smitherman, Todd A; Weinland, Stephan R; Tann, Beverley; Joseph, Petra; Lee, Thomas S; Houle, Timothy T

    2009-05-01

    To evaluate the efficacy of botulinum toxin A (BT-A) as a prophylactic treatment for chronic tension-type headache (CTTH) with myofascial trigger points (MTPs) producing referred head pain. Although BT-A has received mixed support for the treatment of TTH, deliberate injection directly into the cervical MTPs very often found in this population has not been formally evaluated. Patients with CTTH and specific MTPs producing referred head pain were assigned randomly to receive intramuscular injections of BT-A or isotonic saline (placebo) in a double-blind design. Daily headache diaries, pill counts, trigger point pressure algometry, range of motion assessment, and responses to standardized pain and psychological questionnaires were used as outcome measures; patients returned for follow-up assessment at 2 weeks, 1 month, 2 months, and 3 months post injection. After 3 months, all patients were offered participation in an open-label extension of the study. Effect sizes were calculated to index treatment effects among the intent-to-treat population; individual time series models were computed for average pain intensity. The 23 participants reported experiencing headache on a near-daily basis (average of 27 days/month). Compared with placebo, patients in the BT-A group reported greater reductions in headache frequency during the first part of the study (P = .013), but these effects dissipated by week 12. Reductions in headache intensity over time did not differ significantly between groups (P = .80; maximum d = 0.13), although a larger proportion of BT-A patients showed evidence of statistically significant improvements in headache intensity in the time series analyses (62.5% for BT-A vs 30% for placebo). There were no differences between the groups on any of the secondary outcome measures. The evidence for BT-A in headache is mixed, and even more so in CTTH. However, the putative technique of injecting BT-A directly into the ubiquitous MTPs in CTTH is partially supported

  14. Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

    OpenAIRE

    Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

    2016-01-01

    Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host ...

  15. 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

  16. The global pertussis initiative: Meeting report from the Regional Latin America Meeting, Costa Rica, 5-6 December, 2008.

    Science.gov (United States)

    Ulloa-Gutierrez, Rolando; Hozbor, Daniela; Avila-Aguero, Maria L; Caro, Jaime; Wirsing von König, Carl-Heinz; Tan, Tina; Plotkin, Stanley

    2010-11-01

    Pertussis remains endemic across the world, with an estimated 279,000 deaths in 2002, the majority in infants under 1 year of age. Worldwide epidemiologic data indicates increasing infection rates in older children and adults, which act as a source of infection to young infants. The Global Pertussis Initiative (GPI) is an expert scientific forum, which has published consensus recommendations for the monitoring, prevention, and treatment of the disease. This paper reports the proceedings of a regional meeting, held in Costa Rica in December 2008. The meeting gathered information on regional epidemiological, diagnostic capabilities and the ability to introduce GPI recommended vaccine strategies in Latin America. The capacity of Latin American countries to conduct vaccination programs is high and there is considerable government support. Whole-cell pertussis vaccines are used across Latin America, which appear to be quite effective. A 4-dose schedule is typically used (2, 4, 6, and 18 months), and a booster given at 4 to 6 years of age, with coverage often above 90%, but with regions of low coverage due to political and geographical difficulties. Adequate surveillance is lacking in many countries, giving insufficient data to guide vaccination policy. Improvements are being made, with countries such as Costa Rica, Panama, and Argentina introducing polymerase chain reaction (PCR) diagnosis. Those countries that do not currently use a preschool booster should launch one. Implementing vaccination programs in adolescents and/or adults to reduce exposure to infants would be beneficial and possible in most countries, given their current infrastructure.

  17. Communication and mass vaccination strategies after pertussis outbreak in rural Amish communities-Illinois, 2009-2010.

    Science.gov (United States)

    Medina-Marino, Andrew; Reynolds, Debra; Finley, Carol; Hays, Susan; Jones, Jane; Soyemi, Kenneth

    2013-01-01

    During January 2010, 2 infants from an Amish community in east-central Illinois were hospitalized with pertussis. The local health department (LDH) intervened to control disease transmission, identify contributing factors, and determine best communications methods to improve vaccination coverage. A retrospective cohort study was conducted using public health surveillance data to determine the extent of the outbreak; the standard Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists case definition for pertussis was used. The standardized Illinois Department of Public Health pertussis patient interview form was used to collect demographic, symptom, vaccination history, and treatment history information. To control disease transmission, LDH staff worked with the Amish community to promote a vaccination campaign during February 6-April 30, 2010. Forty-seven cases were identified, with onsets during December 2009-March 2010. Median age was 7 (interquartile range 1-12) years. Nineteen (40%) patients were male; 39 (83%) were aged communication and outreach resulted in a successful vaccine campaign and long-running monthly vaccination clinic. Amish do not universally reject vaccines, and their practices regarding vaccination are not static. No claim to original US government works.

  18. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Schure, Rose-Minke; Ozturk, Kemal; de Rond, Lia G. H.; de Greeff, S. C.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12

  19. 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.

  20. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    Science.gov (United States)

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  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. Whooping cough in Pakistan: Bordetella pertussis vs Bordetella parapertussis in 2005-2009.

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    Bokhari, Habib; Said, Fahad; Syed, Muhammad A; Mughal, Amjad; Kazi, Yasmeen F; Heuvelman, Kees; Mooi, Frits R

    2011-10-01

    Pertussis, or whooping cough, is an acute respiratory disease mainly affecting infants and children and is caused by Bordetella pertussis and Bordetella parapertussis. The aim of this study was to investigate the share of Bordetella species from potential whooping cough cases during 2005-2009. Eight hundred and two samples from suspected pertussis cases were collected, mainly from 2 provinces of Pakistan. Bacterial culture, identification, DNA extraction and routinely used polymerase chain reaction (PCR) methods using IS1001, IS1002 and IS481 were used to identify the Bordetella species. The results were unexpected, because all of the isolates collected from the different cities were identified as B. parapertussis (7.4%); B. pertussis was not isolated from any sample. However, PCR results indicated the presence of a small percentage (0.6%) of B. pertussis among the total cases studied. This study suggests that vaccines to protect against both B. pertussis and B. parapertussis should be considered.

  3. Re-emergence of diphtheria and pertussis: implications for Nigeria.

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    Sadoh, A E; Oladokun, R E

    2012-11-26

    In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

  4. Botulinum toxin: The Midas touch.

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    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.

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

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    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.

  6. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity.

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    Fedele, Giorgio; Schiavoni, Ilaria; Adkins, Irena; Klimova, Nela; Sebo, Peter

    2017-09-21

    Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

  7. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity

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    Giorgio Fedele

    2017-09-01

    Full Text Available Adenylate cyclase toxin (CyaA is released in the course of B. pertussis infection in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC, macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3′,5′-cyclic adenosine monophosphate (cAMP, which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

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

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    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.

  9. Assessing determinants of the intention to accept a pertussis cocooning vaccination: A survey among Dutch parents.

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    Visser, Olga; Kraan, Janneke; Akkermans, Reinier; Ruiter, Robert A C; van der Velden, Koos; Hautvast, Jeannine L A; Hulscher, Marlies E J L

    2016-09-07

    Pertussis cocooning is one of the strategies aiming to prevent the potential harm of pertussis in infants by vaccinating (among others) their parents. Several countries adopted this strategy, but uptake is a problem. Determinants of parental uptake are important in the design of an effective vaccination programme. Therefore, this study aims to assess parents' intention to accept a pertussis cocooning vaccination and its determinants. A 98 item questionnaire was developed based on a theoretical framework, assessing parents' intention to accept a pertussis cocooning vaccination and its personal and psychosocial determinants. In addition, beliefs underlying parents' attitude towards pertussis cocooning vaccination were assessed. Both logistic and linear regression analysis were used to assess univariate and multivariate associations amongst study variables. Parents returned 282 questionnaires. The majority of the parents (78%) reported a positive intention to accept a pertussis cocooning vaccination. Attitude (OR 6.6, pexpectations (β 0.15, p.011) were significant correlates of attitude towards pertussis cocooning vaccination. The parental intention to accept a pertussis cocooning vaccination in this study is rather high. Targeting the identified determinants of parents' acceptance in a pertussis cocooning vaccination programme is crucial to secure that intention is translated into actual vaccination uptake. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Attitudes, knowledge and perceptions towards whooping cough and pertussis vaccine in hospitalized adults.

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    Ridda, Iman; Gao, Zhanhai; Macintyre, C Raina

    2014-02-19

    Whooping cough or pertussis is a major cause of morbidity and mortality for adults and children around the world. There has been a rise in pertussis-related deaths in the elderly; pertussis vaccination is not currently routinely recommended in adults, excepting new parents and other adults household members including grandparents and care-givers of young children. Currently, there is lack of clear vaccine recommendations after the age of 50 years. Given the increase in adult pertussis, adult vaccine recommendations are a policy consideration. The study surveyed a convenience sample of patients previously recruited in a case control study designed to examine the burden of influenza with and without AMI in adults aged ≥ 40 years. Our findings showed that only 9.6% had received the pertussis vaccination within the past five years and 79.4% of participants had no knowledge of the pertussis adult booster vaccine, and 30.7% of participants who had regular contact with children under the age of two years in the past 12 months. The results showed that even though there is general acceptance of prevention by vaccines, there is low awareness about pertussis vaccination. This lack of knowledge presents a barrier against pertussis vaccination thus it is imperative that any future adult immunisation policy recommendations around pertussis vaccine include awareness programs in the target population. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department [digest].

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    Zibners, Lara; Chaudhari, Pradip

    2017-02-22

    Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

  12. Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

    Science.gov (United States)

    Crespo, Inma; Broner, Sonia; Soldevila, Núria; Martínez, Ana; Godoy, Pere; Sala-Farré, Maria-Rosa; Company, Maria; Rius, Cristina; Domínguez, Angela; Group Of Catalonia, The Pertussis Working

    2015-01-01

    In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10(-6) persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10(-5) persons-year.   After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10(-6) persons-year) had an index case aged <15 y and 87 (0.87 × 10(-6) person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10-1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10(-6) persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10(-6) person-year) (RR = 0.78, 95%CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.

  13. Laboratory-based surveillance of pertussis using multitarget real-time PCR in Japan: evidence for Bordetella pertussis infection in preteens and teens

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    K. Kamachi

    2015-11-01

    Full Text Available Between January 2013 and December 2014, we conducted laboratory-based surveillance of pertussis using multitarget real-time PCR, which discriminates among Bordetella pertussis, Bordetella parapertussis, Bordetella holmesii and Mycoplasma pneumoniae. Of 355 patients clinically diagnosed with pertussis in Japan, B. pertussis, B. parapertussis and M. pneumoniae were detected in 26% (n = 94, 1.1% (n = 4 and 0.6% (n = 2, respectively, whereas B. holmesii was not detected. It was confirmed that B. parapertussis and M. pneumoniae are also responsible for causing pertussis-like illness. The positive rates for B. pertussis ranged from 16% to 49%, depending on age. Infants aged ≤ 3 months had the highest rate (49%, and children aged 1 to 4 years had the lowest rate (16%, p < 0.01 vs. infants aged ≤ 3 months. Persons aged 10 to 14 and 15 to 19 years also showed high positive rates (29% each; the positive rates were not statistically significant compared with that of infants aged ≤ 3 months (p ≥ 0.06. Our observations indicate that similar to infants, preteens and teens are at high risk of B. pertussis infection.

  14. Treatment of an Aedes aegypti colony with the Cry11Aa toxin for 54 generations results in the development of resistance

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    Gloria Cadavid-Restrepo

    2012-02-01

    Full Text Available To study the potential for the emergence of resistance in Aedes aegypti populations, a wild colony was subjected to selective pressure with Cry11Aa, one of four endotoxins that compose the Bacillus thuringiensis serovar israelensis toxin. This bacterium is the base component of the most important biopesticide used in the control of mosquitoes worldwide. After 54 generations of selection, significant resistance levels were observed. At the beginning of the selection experiment, the half lethal concentration was 26.3 ng/mL and had risen to 345.6 ng/mL by generation 54. The highest rate of resistance, 13.1, was detected in the 54th generation. Because digestive proteases play a key role in the processing and activation of B. thuringiensis toxin, we analysed the involvement of insect gut proteases in resistance to the Cry11Aa B. thuringiensis serovar israelensis toxin. The protease activity from larval gut extracts from the Cry11Aa resistant population was lower than that of the B. thuringiensisserovar israelensis susceptible colony. We suggest that differences in protoxin proteolysis could contribute to the resistance of this Ae. aegypti colony.

  15. 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...

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

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    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.

  18. CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

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    Roy Monica

    2012-01-01

    Full Text Available Abstract Background Granulocytes generally exert protective roles in the central nervous system (CNS, but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE, the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined. Methods CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques. Results CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS or pertussis toxin (PTX, the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease. Conclusions This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.

  19. Marine and freshwater toxins.

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    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

  20. Update on botulinum toxin and dermal fillers.

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    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.

  1. Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants.

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    Olga Visser

    Full Text Available Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially <6 months at risk of severe complications, because they are too young to be fully protected by vaccination. The global pertussis initiative has proposed pertussis vaccination of young infants' close contacts, in order to reduce pertussis transmission and the burden of the disease on infants. Our aim is to explore the perceived determinants (barriers and facilitators of intention to accept vaccination among the possible target groups of pertussis vaccination for cocooning. Consideration of these determinants is necessary to optimise the uptake of the vaccination.We conducted 13 focus groups and six individual semi-structured interviews with members of possible target groups for pertussis cocooning (i.e. parents, maternity assistants, midwives, and paediatric nurses in the Netherlands. Here, both maternal pertussis vaccination as well as pertussis cocooning has not been implemented. The topic list was based on a literature review and a barrier framework. All interviews were transcribed verbatim and two researchers performed thematic content analysis.The participants' risk perception, outcome expectations, general vaccination beliefs, moral norms, opinion of others, perceived autonomy, anticipated regret, decisional uncertainty, and perceived organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning.This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations, justice (as a concept of moral norms, anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as

  2. Toxins of filamentous fungi.

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    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

  3. Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.

    Science.gov (United States)

    Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

    2017-01-02

    An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel

  4. Cost-Effectiveness Analysis of Various Pertussis Vaccination Strategies Primarily Aimed at Protecting Infants in the Netherlands

    NARCIS (Netherlands)

    Westra, Tjalke A.; de Vries, Robin; Tamminga, Johannes J.; Sauboin, Christophe J.; Postma, Maarten J.

    Background: Pertussis is a highly contagious respiratory disease. Despite a high rate of vaccine coverage through the Dutch national immunization program, the incidence of pertussis remains high in the Netherlands and the risk of infection continues. Because pertussis is most severe in unimmunized

  5. Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

    NARCIS (Netherlands)

    Melker, de H.

    1999-01-01

    In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.

    In a

  6. Assessing determinants of the intention to accept a pertussis cocooning vaccination: A survey among Dutch parents

    NARCIS (Netherlands)

    Visser, O.; Kraan, J.; Akkermans, R.P.; Ruiter, R.A.; Velden, K. van der; Hautvast, J.L.A.; Hulscher, M.E.J.L.

    2016-01-01

    INTRODUCTION: Pertussis cocooning is one of the strategies aiming to prevent the potential harm of pertussis in infants by vaccinating (among others) their parents. Several countries adopted this strategy, but uptake is a problem. Determinants of parental uptake are important in the design of an

  7. Pertussis resurgence: waning immunity and pathogen adaptation - two sides of the same coin

    NARCIS (Netherlands)

    Mooi, F.R.; Maas, N. van der; Melker, H.E. de

    2014-01-01

    SUMMARY Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate of Bordetella pertussis poses a threat to infants that have not been (completely) vaccinated

  8. Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

    Science.gov (United States)

    Sedighi, Iraj; Karimi, Abdollah; Amanati, Ali

    2016-01-01

    Context Universal immunization against Bordetella pertussis has partially controlled the burden of the disease and its transmission. However, according to recent data, the epidemiology of this vaccine-preventable disease has changed. Now, younger infants, adolescents, and adults are at greater risk of infection. This article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention. Evidence Acquisition In this narrative review, the most recently published sources of information on pertussis control measures, consisting of textbooks and articles, have been reviewed. We focused on the more recent data about the changing epidemiology or pertussis in Scopus through the use of the MeSH-term words [pertussis] or [whooping cough] and [epidemiology] or [outbreak] or [resurgence], but our search was not restricted to this particular strategy; we also tried to find all of the most recent available data in the general field through other means. Results Primary and booster doses of the pertussis vaccine seem to partially control transmission of the disease, but despite the different preventive strategies available, pertussis continues to cause mortality and morbidity among high-risk groups. Conclusions Adding booster doses of acellular pertussis vaccine to the current national immunization practices with whole-cell vaccines for young adults and pregnant women seems to be a good option for controlling mortality and morbidity among high-risk groups such as very young infants. PMID:27729960

  9. Pertussis in infancy and the association with respiratory and cognitive disorders at toddler age.

    Science.gov (United States)

    de Greeff, Sabine C; van Buul, Laura W; Westerhof, Anneke; Wijga, Alet H; van de Kassteele, Jan; Oostvogels, Bregje; van der Maas, Nicoline A T; Mooi, Frits R; de Melker, Hester E

    2011-10-26

    Pertussis in unvaccinated infants can run a severe course and is often accompanied by complications. In this pilot study, we studied whether there is an association between pertussis hospitalisation in infancy and, respiratory symptoms, growth and cognitive development in early childhood. A group of 89 children aged 13-45 months and hospitalised for laboratory confirmed pertussis within the first six months of their life were compared with 172 children without a history of pertussis. Risk ratios (RR) with 95% confidence intervals (CI) of the association between health outcomes and pertussis in infancy were calculated. Weight-for-length and length-for-age z-scores were calculated to investigate growth. Van Wiechen scores were compared to study cognitive development. Children with a history of pertussis in infancy had a greater chance on "asthma symptoms" (RR 2.8 95%CI 1.1-7.0) on toddler age and were more likely to report "respiratory infections" (RR 3.3 95%CI 1.6-6.6). In addition, children with a history of pertussis in infancy had significantly lower weight-for-height in the first 40 months of life. No significant differences in cognitive development were found. We found an association between severe pertussis in infancy and respiratory symptoms on toddler age. The mechanisms that may underlie this association require further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Diffusion of Botulinum Toxins

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    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.

  11. 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...

  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. Epidemiology of pertussis in Casablanca (Morocco): contribution of conventional and molecular diagnosis tools.

    Science.gov (United States)

    Katfy, Khalid; Guiso, Nicole; Diawara, Idrissa; Zerouali, Khalid; Slaoui, Bouchra; Jouhadi, Zineb; Zineddine, Abdelhadi; Belabbes, Houria; Elmdaghri, Naima

    2017-05-16

    Pertussis, a vaccine preventable disease, is still responsible of significant morbidity and mortality around the world, mostly in newborns. The aim of the present study was (1) to introduce pertussis surveillance in the major pediatric hospital of Casablanca (2) to analyze the prevalence of pertussis among children under 14 years of age and their entourage in Casablanca, Morocco. This is a prospective and non-case controlled study, including children suspected of Pertussis admitted at the Abderrahim Harouchi Pediatric Hospital in Casablanca, from January 2013 to June 2015. Nasopharyngeal samples were obtained for Bordetella spp. culture and Real time PCR detection (RT-PCR) with specific primers of Bordetella spp., B. pertussis, B. parapertussis and B. holmesii. The detection of Bordetella spp. was also performed in some household contacts of the children suspected of pertussis. During the 2.5-years period, a total of 282 samples were collected from hospitalized children (156) and in some of their contacts (126). Among 156 samples from the children (from whom 57% were under 2 month of age), Bordetella DNA was detected in 61% (96/156) by RT-PCR. Among these positive samples, 91.7% (88/96) corresponded to B. pertussis DNA. Furthermore, in 39.5% (38/96) of the Bordetella positive samples, B. holmesii DNA was also detected. B. parapertussis DNA was detected in only one sample (1/156). Out of the 156 samples collected from the hospitalized children, only 48 were tested by culture, and 4 B. pertussis were isolated (8.3%). Among the 126 samples from the contacts of the children, mostly mothers (115 cases), Bordetella DNA was detected in 47% (59/126), 90% (53/59) being B. pertussis DNA. Moreover, B. holmesii DNA was also detected in 18.6% (11/59) of the Bordetella positive samples, and coexistence of B. pertussis and B. holmesii DNA in 36.5% (35/96). Two B. pertussis were isolated by culture performed on 43 samples of the contacts of the children (4.6%). This study

  14. 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.

  15. Cholera toxin-induced ADP-ribosylation of a 46 kDa protein is decreased in brains of ethanol-fed mice

    International Nuclear Information System (INIS)

    Nhamburo, P.T.; Hoffman, P.L.; Tabakoff, B.

    1988-01-01

    The acute in vitro effects of ethanol on cerebral cortical adenylate cyclase activity and beta-adrenergic receptor characteristics suggested a site of action of ethanol at Gs, the stimulatory guanine nucleotide binding protein. After chronic ethanol ingestion, the beta-adrenergic receptor appeared to be uncoupled (i.e., the form of the receptor with high affinity for agonist was undetectable), and stimulation of adenylate cyclase activity by isoproterenol or guanine nucleotides was reduced, suggesting an alteration in the properties of Gs. To further characterize this change, cholera and pertussis toxin-mediated 32 P-ADP-ribosylation of mouse cortical membranes was assessed in mice that had chronically ingested ethanol in a liquid diet. 32 P-labeled proteins were separated by SDS-PAGE and quantitated by autoradiography. There was a selective 30-50% decrease in cholera toxin-induced labeling of 46 kDa protein band in membranes of ethanol-fed mice, with no apparent change in pertussis toxin-induced labeling. The 46 kDa protein has a molecular weight similar to that of the alpha subunit of Gs, suggesting a reduced amount of this protein or a change in its characteristics as a substrate for cholera toxin-induced ADP-ribosylation in cortical membranes of ethanol-fed mice

  16. Pertussis incidence rates in Novi Sad (Serbia before and during improved surveillance

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    Petrović Vladimir

    2017-01-01

    Full Text Available Introduction/Objective. The Global Pertussis Initiative (GPI proposed clinical case definitions for pertussis diagnosis in three different age cohorts in order to improve surveillance of pertussis especially in older children, adolescents, and adults. The main goal of this research was to compare the burden of pertussis in the city of Novi Sad before and after the introduction of improved surveillance using the GPI clinical case definitions of pertussis. Methods. Baseline data on pertussis were obtained from routine (non-sentinel reporting before improved surveillance was introduced. From September 16, 2012, clinical case definitions proposed by GPI were applied within improved (sentinel and hospital surveillance, while surveillance clinical case definitions were not introduced within non-sentinel. To confirm the suspected diagnosis, sampling of nasopharyngeal swab and/or blood was obtained from all cases. The choice of laboratory method (PCR or ELISA depended on the duration of coughing and the age of the patients. Data were statistically processed by SPSS Statistics, version 22. Results. During the 12-year period before the introduction of improved surveillance, only two clinical pertussis cases were registered. In contrast, during the two-year period of improved surveillance, a total of 14 (season 2012/13 and 146 (season 2013/2014 confirmed pertussis cases were reported. Significant differences were determined in distribution of pertussis according to the type of surveillance and the level of health care. Conclusion. Introduction of clinical case definitions proposed by GPI improved the quality of surveillance and enabled an insight in the distribution of pertussis in all age groups and at all levels of health care.

  17. Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.

    Science.gov (United States)

    Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody

    2017-06-03

    Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.

  18. Respiratory viral infections in infants with clinically suspected pertussis

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    Angela E. Ferronato

    2013-11-01

    Full Text Available Objective: to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. Methods: a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP (polymerase chain reaction/culture and for respiratory viruses (RVs (immunofluorescence were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Results: Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. Conclusion: the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Resumo: Objetivo: avaliar a frequência das infecções por vírus respiratórios em lactentes hospitalizados com suspeita clínica de coqueluche e analisar suas características admissionais e evolutivas. Métodos: foi realizado um estudo de coorte histórica, em um serviço sentinela para coqueluche, no qual a pesquisa de v

  19. Bordetella pertussis, B. parapertussis, vaccines and cycles of whooping cough.

    Science.gov (United States)

    Bouchez, Valérie; Guiso, Nicole

    2015-10-01

    Whooping cough is a vaccine-preventable disease due to Bordetella pertussis and B. parapertussis. This highly contagious respiratory disease occurs through epidemic cycles every 3-5 years and vaccination did not change this frequency. Models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. However, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine pressure might also play an important role. These parameters are discussed in this review. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. El Gran Catharro de 1580 ¿gripe o pertussis?

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    Camaño Puig, Ramón

    2005-12-01

    Full Text Available The gran Catharro (1580 is considered the first influenza epidemic. The analysis of various testimonies of the time may offer some doubts about whether or not it was so; and data strongly support that it was a pertussis epidemic.

    El Gran Catharro (1580 es considerado como la primera epidemia de gripe. El análisis conjunto de los datos contenidos en diferentes testimonios, suscita dudas respecto a que se tratara de una epidemia de gripe y apoyan la posibilidad de que se tratara de una de tos ferina.

  1. 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.

  2. Cosmetic Effect of Botulinum Toxin In Focal Hyperhydrosis

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    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.

  3. 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.

  4. Examining the role of different age groups, and of vaccination during the 2012 Minnesota pertussis outbreak

    Science.gov (United States)

    Worby, Colin J.; Kenyon, Cynthia; Lynfield, Ruth; Lipsitch, Marc; Goldstein, Edward

    2015-01-01

    There is limited information on the roles of different age groups during pertussis outbreaks. Little is known about vaccine effectiveness against pertussis infection (both clinically apparent and subclinical), which is different from effectiveness against reportable pertussis disease, with the former influencing the impact of vaccination on pertussis transmission in the community. For the 2012 pertussis outbreak in Minnesota, we estimated odds ratios for case counts in pairs of population groups before vs. after the epidemic’s peak. We found children aged 11–12y, 13–14y and 8–10y experienced the greatest rates of depletion of susceptible individuals during the outbreak’s ascent, with all ORs for each of those age groups vs. groups outside this age range significantly above 1, with the highest ORs for ages 11–12y. Receipt of the fifth dose of DTaP was associated with a decreased relative role during the outbreak’s ascent compared to non-receipt [OR 0.16 (0.01, 0.84) for children aged 5, 0.13 (0.003, 0.82) for ages 8–10y, indicating a protective effect of DTaP against pertussis infection. No analogous effect of Tdap was detected. Our results suggest that children aged 8–14y played a key role in propagating this outbreak. The impact of immunization with Tdap on pertussis infection requires further investigation. PMID:26278132

  5. Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication

    Directory of Open Access Journals (Sweden)

    Leonie Schnell

    2016-07-01

    Full Text Available Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenylsemicarbazone (EGA has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT. Here, we demonstrate that EGA also protects human cells from diphtheria toxin by inhibiting the pH-dependent translocation of DTA across cell membranes. The results suggest that EGA might serve for treatment and/or prevention of the severe disease diphtheria.

  6. Pertussis prevalence and its determinants among children with persistent cough in urban Uganda.

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    Vincent Kayina

    Full Text Available We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR and ELISA serology tests.Pertussis prevalence was 67 (15% (95% Confidence Interval (CI: 12-18 and 81 (20% (95% CI: 16-24 by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30% had a coughing household member and 316 (70% did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR 7.16 (95% CI: 1.24-41.44. Among the 316 children that did not have a coughing household member, age 40 years of age were the factors associated with pertussis. Age 59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.

  7. Prevalence of Bordetella pertussis and Bordetella parapertussis in Samples Submitted for RSV Screening

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    Walsh, Paul

    2008-08-01

    Full Text Available BACKGROUND: The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV; however, management differs.HYPOTHESIS: First, the prevalence of B. pertussis is less than 2% among patients screened for RSV, and second the prevalence of B. parapertussis is also less than 2% among these patients.METHODS: Nasal washings submitted to a clinical laboratory for RSV screening were tested for B. pertussis and B. parapertussis, using species-specific real-time polymerase chain reaction (PCR assays. These were optimized to target conserved regions within a complement gene and the CarB gene, respectively. A Bordetella spp. genus-specific real-time PCR assay was designed to detect the Bhur gene of B. pertussis, B. parapertussis, and B. bronchiseptica. RSV A and B subtypes were tested by reverse transcription-PCR.RESULTS: Four hundred and eighty-nine clinical samples were tested. There was insufficient material to complete testing for one B. pertussis, 10 RSV subtype A, and four RSV subtype B assays. Bordetella pertussis was detected in 3/488 (0.6% (95% CI 0.1% to 1.8%, while B. parapertussis was detected in 5/489 (1.0% (95% CI 0.3% to 2.4%. Dual infection of B. pertussis with RSV and of B. parapertussis with RSV occurred in two and in three cases respectively. RSV was detected by PCR in 127 (26.5%.CONCLUSION: The prevalence of B. pertussis in nasal washings submitted for RSV screening was less than 2%. The prevalence of parapertussis may be higher than 2%. RSV with B. pertussis and RSV with B. parapertussis coinfection do occur.

  8. Changing spatial epidemiology of pertussis in continental USA.

    Science.gov (United States)

    Choisy, Marc; Rohani, Pejman

    2012-11-22

    Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading.

  9. 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.

  10. [SAFETY AND IMMUNOGENICITY OF A NATIONAL COMBINED VACCINE AGAINST PERTUSSIS, DIPHTHERIA, TETANUS, HEPATITIS B AND Hib-INFECTION, CONTAINING ACELLULAR PERTUSSIS COMPONENT, DURING IMMUNIZATION OF ADULTS].

    Science.gov (United States)

    Feldblyum, I V; Nikolaeva, A M; Pavroz, K A; Danilina, T V; Sosnina, O Yu; Vyaznikova, T V; Ershov, A E; Trofimov, D M; Polushkina, A V

    2016-01-01

    Study safety, reactogenicity and immunologic effectiveness of a national combined vaccine against diphtheria, pertussis (acellular component), tetanus, hepatitis B and Hib-infection during immunization of volunteers aged 18-60 years. The study was carried out in accordance with ethical standards and requirements, regulated by Helsinki declaration and Good clinical practice (ICHGCP). In a simple non-randomized clinical trial 20 adult volunteers took part, the mean age of those was 46.9 years. Registered: post-vaccination reactions (both local and systemic) were mild and of moderate degree of severity, stopped independently after 2-3 days without administration of drug treatment. Postvaccinal complications were not noted. Parameters of general and biochemical analysis of blood, urine, IgE content in dynamics of immunization were within normal limits. A single administration of aAPDT--HepB+Hib to individuals aged 18-60 years resulted in development of antibodies against all the components of the preparation. Seroconversion factor fluctuated from 6.9 to 53.5: The results obtained allow to recommend the vaccine for evaluation of its safety, reactogenicity, immunologic and prophylaxis effectiveness in randomized clinical observation trials in children.

  11. 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.

  12. Botulinum toxin for treatment of cocontractions related to obstetrical brachial plexopathy Toxina botulínica para tratamento das co-contrações relacionadas à plexopatia braquial obstétrica

    Directory of Open Access Journals (Sweden)

    Carlos O. Heise

    2005-09-01

    Full Text Available Botulinum toxin type A was recently introduced for treatment of biceps - triceps muscle cocontraction, which compromises elbow function in children with obstetrical brachial plexopathy. This is our preliminary experience with this new approach. Eight children were treated with 2 - 3 U/kg of botulinum toxin injected in the triceps (4 patients and biceps (4 patients muscle, divided in 2 or 3 sites. All patients submitted to triceps injections showed a long-lasting improvement of active elbow flexion and none required new injections, after a follow-up of 3 to 18 months. Three of the patients submitted to biceps injections showed some improvement of elbow extension, but none developed anti-gravitational strength for elbow extension and the effect lasted only three to five months. One patient showed no response to triceps injections. Our data suggest that botulinum toxin can be useful in some children that have persistent disability secondary to obstetrical brachial plexopathy.A toxina botulínica do tipo A foi introduzida recentemente para o tratamento das co-contrações entre os músculos biceps e triceps, que comprometem a função do cotovelo nas crianças com plexopatia braquial obstétrica. Apresentamos nossa experiência preliminar com esta abordagem. Oito crianças foram tratadas com 2 - 3 U/kg de toxina botulínica injetada nos músculos triceps (4 pacientes e biceps (4 pacientes, divididas em 2 ou 3 sítios. Todos os pacientes submetidos a injeções no triceps apresentaram melhora persistente da flexão do cotovelo e nenhum precisou de novas aplicações após seguimento de 3 a 18 meses. Três pacientes submetidos a aplicações no biceps apresentaram melhora na extensão do cotovelo, mas nenhum adquiriu força antigravitacional e o efeito durou apenas 3 a 5 meses. Um paciente não respondeu às injeções. Nossos dados sugerem que a toxina botulínica pode ser útil no tratamento de algumas crianças com seqüelas de plexopatia braquial

  13. The BvgAS Regulon of Bordetella pertussis

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    Kyung Moon

    2017-10-01

    Full Text Available Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P, and virulence-activated genes (vags are expressed [Bvg(+ mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs are induced [Bvg(− mode]. Here, we have used transcriptome sequencing (RNA-seq and reverse transcription-quantitative PCR (RT-qPCR to define the BvgAS-dependent regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as kdpED, multiple other transcriptional regulators, and the extracytoplasmic function (ECF sigma factor brpL, which is needed for type 3 secretion system (T3SS expression, further establishing the importance of BvgA~P as an apex regulator of transcriptional networks promoting virulence. Using in vitro transcription, we demonstrate that the promoter for brpL is directly activated by BvgA~P. BvgA-FeBABE cleavage reactions identify BvgA~P binding sites centered at positions −41.5 and −63.5 in bprL. Most importantly, we show for the first time that genes for multiple and varied metabolic pathways are significantly upregulated in the B. pertussis Bvg(− mode. These include genes for fatty acid and lipid metabolism, sugar and amino acid transporters, pyruvate dehydrogenase, phenylacetic acid degradation, and the glycolate/glyoxylate utilization pathway. Our results suggest that metabolic changes in the Bvg(− mode may be participating in bacterial survival, transmission, and/or persistence and identify over 200 new vrgs that can be tested for function.

  14. Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants.

    Science.gov (United States)

    Visser, Olga; Hautvast, Jeannine L A; van der Velden, Koos; Hulscher, Marlies E J L

    2016-01-01

    Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning. This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations), justice (as a concept of moral norms), anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as predominant themes within these determinants. These themes require particular attention in future research on vaccination acceptance, especially with regard to their role in use and implementation in policy and practice.

  15. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick

  16. Risk of Brain Damage Following Pertussis Immunization with Whole-Cell cf Acellular Vaccines

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    J Gordon Millichap

    2004-06-01

    Full Text Available Serious neurological disorders reported following whole-cell (WC in comparison to acellular (AC pertussis vaccines (PV were evaluated by the Genetic Centers of America, Silver Spring, MD.

  17. Pertussis Reinfection in an Adult: A Cause of Persistent Cough Not to Be Ignored

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    Theocharis Koufakis

    2017-01-01

    Full Text Available Pertussis is traditionally considered as a disease of the childhood; however, accumulating evidence suggests a stable increase of its incidence among adults and adolescents, during the last decades. Despite the fact that reinfection after natural disease or vaccination is not uncommon, the index of clinical suspicion of pertussis diagnosis in adults remains low. In this article, we report a case of pertussis reinfection 30 years after natural infection, which was complicated by pneumonia, and we discuss our diagnostic and therapeutic approach, aiming to raise clinicians’ degree of suspicion regarding pertussis diagnosis in adults. Prompt recognition and appropriate therapy of adult patients can result in the effective control of the symptoms, prevention of severe complications, and spread of the infection to children; thus, they are of great clinical and public health importance.

  18. Hospitalizations and deaths due to pertussis in children from 1996 to 2013

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    Janayne F. Mançaneira

    2016-01-01

    Conclusions: There was a substantial increase in hospitalizations and deaths from pertussis in children for three consecutive years (2011, 2012, and 2013 in all Brazilian regions. The most affected age group was that of children younger than one year.

  19. Toxin-Based Therapeutic Approaches

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    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.

  20. 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