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ABSTRACT: Immunologic interventions in a subset of breast cancer patients represent a well-established therapeutic approach reflecting individualized treatment modalities. Thus, the therapeutic administration of monoclonal antibodies targeting tumor-associated antigens (TAA), such as Her-2/neu, represents a milestone in cancer treatment. However, passive antibody administration suffers from several drawbacks, including frequency and long duration of treatment. These undesirables may be avoidable in an approach based on generating active immune responses against these same targets. Only recently has the significance of tumors in relation to their microenvironments been understood as essential for creating an effective cancer vaccine. In particular, the immune system plays an important role in suppressing or promoting tumor formation and growth. Therefore, activation of appropriate triggers (such as induction of Th1 cells, CD8+ T cells, and suppression of regulatory cells in combination with generation of antibodies with anti-tumor activity) is a desirable goal. Current vaccination approaches have concentrated on therapeutic vaccines using certain TAA. Many cancer antigens, including breast cancer antigens, have been described and also given priority ranking for use as vaccine antigens by the US National Cancer Institute. One of the TAA antigens which has been thoroughly examined in numerous trials is Her-2/neu. This review will discuss delivery systems for this antigen with special focus on T and B cell peptide vaccines. Attention will be given to their advantages and limitations, as well as the use of certain adjuvants to improve anti-cancer responses.
Breast Cancer Research and Treatment 01/2013; · 4.43 Impact Factor
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ABSTRACT: In a sample of originally 430 healthy adults (18-84 years of age) with documented basic and booster immunization against tick borne encephalitis, cumulative seroprotection rates 8 (n=178) and 10 years (n=183) after the last booster dose were 86.8% and 77.3% according to the neutralization test, respectively. In subjects aged 50 years and older, antibody titers were significantly lower compared to subjects younger than 50 years. History of any allergy but not previous exposure to other flaviviral antigens was associated with higher neutralization titers. In subjects with waning immunity, a single booster dose induced a strong anamnestic antibody response.
Vaccine 01/2013; · 3.77 Impact Factor
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ABSTRACT: IgE antibody-mediated allergies affect more than 25% of the population worldwide. To investigate therapeutic and preventive effects of passive immunization with allergen-specific IgG antibodies on allergy in mouse models we used clinically relevant pollen allergens. In a treatment model, mice were sensitized to the major birch pollen allergen Bet v 1 and to the major grass pollen allergens, Phl p 1 and Phl p 5 and then received passive immunization with rabbit IgG antibodies specific for the sensitizing or an unrelated allergen. In a prevention model, mice obtained passive immunization with allergen-specific rabbit IgG before sensitization. Kinetics of the levels of administered IgG antibodies, effects of administered allergen-specific IgG on allergen-specific IgE reactivity, the development of IgE and IgG responses and on immediate allergic reactions were studied by ELISA, rat basophil leukaemia degranulation assays and skin testing, respectively. Treated mice showed an approximately 80% reduction of allergen-specific IgE binding and basophil degranulation which was associated with the levels of administered allergen-specific IgG antibodies. Preventive administration of allergen-specific IgG antibodies suppressed the development of allergen-specific IgE and IgG(1) antibody responses as well as allergen-induced basophil degranulation and skin reactivity. Our results show that passive immunization with allergen-specific IgG antibodies is effective for treatment and prevention of allergy to clinically important pollen allergens in a mouse model and thus may pave the road for the clinical application of allergen-specific antibodies in humans.
Immunobiology 10/2012; · 3.20 Impact Factor
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ABSTRACT: Travelers' diarrhea (TD) is the most important health issue among international travelers. In high risk areas, 50-90% of travelers may experience an episode of TD. The risk of acquiring TD is influenced by factors such as the destination, duration of stay, standard of accommodation, type of travel, age of the traveler, and also by individual risk factors. Most cases of TD are caused by bacteria; treatment for TD are loperamide and antibiotics. Preventive strategies such as hygiene measures have limited impact. Prophylactic intake of antibiotics or vaccines to prevent from TD can be considered in special situations.
Infectious disease clinics of North America 09/2012; 26(3):691-706. · 2.29 Impact Factor
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Herwig Kollaritsch,
Christoph Wenisch,
Christoph Hatz,
Gunther von Laer,
Bernd Bauer,
Ursula Hollenstein,
Martin Haditsch,
Gerhard Diridl,
Waldemar Malinowski,
Eva Jeschko,
Gabriela Payer-Neundlinger,
Nicole Speiser-Remp,
Hannes E. T. Pichler,
Helmut Rumpold,
Heinrich Stemberger,
Gerald Eder,
Gerhard Wiedermann, Ursula Wiedermann
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ABSTRACT: Ein standardisiertes Vorgehen bei medizinischen Untersuchungen für Personen, die für längere Zeit ins Ausland gehen, um dort
berufliche oder private Aufgaben wahrzunehmen, ist derzeit im deutschsprachigen Raum nicht ausreichend verankert. Das als
Autoren zeichnende Expertengremium versucht, mit Hilfe eines modulartig aufgebauten Untersuchungsprogramms ein möglichst flexibles
System für die per Definition festgelegte "Entsendungseignungsuntersuchung" festzulegen. Dabei werden neben den medizinischen
Grundlagen auch ökonomische und rechtliche Aspekte für eine derartige Untersuchung unter Bedachtnahme auf die unterschiedlichen
Voraussetzungen der Länder Deutschland, Österreich, Schweiz ausgearbeitet. Ergänzt wird die Ausarbeitung des Untersuchungsprogramms
durch Vorschläge zu allgemein gültigen Begriffsdefinitionen rund um Auslandsentsendungen, Definition des Kollektivs der zu
Untersuchenden, der Untersucher, der Standardisierung der Aussage des Untersuchungsergebnisses und der reisemedizinischen
Aspekte.
Standards for medical clearance for private or business missions abroad are – at least in the German speaking countries –
not clearly defined and mostly derived from the old terminus "Tropentauglichkeit" which means fit for mission in the tropics.
The authors now define a new standard, called "Entsendungstauglichkeitsuntersuchung" which means clearance of fitness for
all types of missions abroad, independent of distinct climatic zones. To meet the inhomogenous requirements of different institutions
and different types of missions the medical examination proposed follows a modular structure to optimize economic and medical
use of resources. Moreover, as Austria, Germany and Switzerland have different legal and economic postulates, the medical
examination has to be adapted to the different premises. The definition and description of this special type of "medical clearance
for missions abroad" is supplemented by recommendations for definitions of clients who should undergo such an investigation
and the professionals who should perform this type of investigation. Additionally, results of this type of medical clearance
are defined and prophylactic aspects in terms of pre-travel advice are mentioned.
Wiener klinische Wochenschrift 04/2012; 119:13-25. · 0.81 Impact Factor
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ABSTRACT: Durchfallserkrankungen stellen ein weltweit großes Gesundheitsproblem dar. Besonders betroffen, sowohl in der Häufigkeit wie
auch in der Schwere der Erkrankung, sind Kinder bis zu 5 Jahren in Entwicklungsländern. Bei Reisenden in diese Gebiete spielen
Durchfallserkrankungen ebenfalls eine große Rolle; etwa 20–50 % der Reisenden entwickeln Reisediarrhoe, vorwiegend hervorgerufen
durch Bakterien, Viren oder Protozoen. Bei den bakteriellen Durchfallserkrankungen werden in Abhängigkeit des betreffenden
Landes (Mexiko, Lateinamerika, Afrika, Philippinen) 30–70 % der Fälle durch enterotoxigene E.coli (ETEC) hervorgerufen. Die Pathogenität dieser nicht invasiven Bakterien wird primär durch hitze-stabile (ST) und hitze-labile
(LT) Toxine bedingt, wobei etwa 20 % aller Reisedurchfallserkrankungen durch LT-sezernierende ETEC hervorgerufen werden. Dieses
hitzelabile Toxin hat eine strukturelle Identität und 80 % Sequenzhomologie mit Choleratoxin. Der derzeit am Markt befindliche
orale Choleraimpfstoff (Dukoral®) enthält nebst abgetöteter Choleravibrionen auch die nicht toxische, aber immunogene B-subunit des Cholera Toxins in rekombinanter
Form. Daher ist dieser orale Impfstoff auch für ETEC-Reisediarrhoe von Nutzen. Effizienzberechnungen der Impfung ergaben,
dass bis zu 25 % der Reisenden dadurch gegen Diarrhoe geschützt werden können. Rotaviren (RV) gehören besonders bei Kindern
zu den wichtigsten Durchfallserregern in Industrie- und Entwicklungsländern. Aufgrund der weltweit hohen Inzidenz dieser Durchfallserkrankung
wurden 2 orale Lebendimpf-stoffe gegen Rotaviren entwickelt, die seit 2006 in Europa registriert sind. Aufgrund der Bedeutung
dieser Erkrankung auch in Österreich wurde im österreichischen Impfplan eine allgemeine Impfempfehlung von Säuglingen zwischen
6 und 24 Wochen ausgegeben. Es handelt sich bei den oralen Impfstoffen einerseits um einen attenuierten, humanen, monovalenten
RV-Lebendimpfstoff, der eine breite Kreuzimmunität gegen die gängigsten Serotypen aufweist (Rotarix®), und andererseits um einen attenuierten pentavalenten Lebendimpfstoff, der 5 human-bovine Reassortanten enthält (RotaTeq®). Verträglichkeit und Wirksamkeit der beiden Impfstoffe sind in etwa vergleichbar: die Wirksamkeit gegen schwere RV-Gastroenteritiden
liegt zwischen 85–98 %, bezüglich Verträglichkeit bestand kein Unterscheid zur Placebokontrolle und keine Assoziationen mit
Invaginationen konnten festgestellt werden.
Diarrheal diseases constitute one of the most important health problems worldwide. Children less than 5 years, living in developing
countries, are particularly in danger with respect to the incidence and severity of the gastrointestinal disorders. Travelers
to developing countries are also at risk to develop diarrheal disorders; around 30–50% of them acquire so called "travelers's
diarrhea" caused by bacteria, viruses or protozoa. It has been estimated that approximately 30–70% of diarrhea are due to
bacteria, of which the most frequently detected enteric pathogens are non-invasive, enterotoxigenic Escherichia coli (ETEC). Their exotoxins, the heat stabile (ST) and the heat labile (LT) toxins are in large part responsible for the pathogenicity
of the bacteria. About 20% of cases of traveler's diarrhea are caused by LT producing ETEC. This heat labile toxin exhibits
a 80% sequence homology with cholera toxin. The presently available vaccine against cholera (Dukoral®) contains inactivated Vibrio cholerae bacteria and the recombinant non-toxic B subunit of cholera toxin. Consequently, this vaccine displays also some efficacy
against traveler's diarrhoea with up to 25 % of travelers being protected against this disease. Rotaviruses are the leading
recognized cause of diarrhoea-related illness and deaths among infants worldwide in developing and industrialized countries.
Based on the high incidence of this disease two oral vaccines have been developed and are available in Europe in 2007. Due
to the impact of rotavirus diseases also in Austria vaccination against this disease has been already suggested in the Austrian
vaccination schedules for infants from 6–24 weeks of age. One of the two vaccines, Rotarix®, is an attenuated monovalent vaccine with a broad cross-reactivity against the most frequent serotypes. The second one, RotaTeq®, is a pentavalent attenuated vaccine containing 5 human-bovine reassortants. Both vaccines display 85–98% efficacy against
severe rotavirus disease and an excellent tolerability with no difference in side reactions to the placebo controls, particularly
with respect to intussusceptions.
Wiener Medizinische Wochenschrift 04/2012; 157(5):102-106.
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ABSTRACT: Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.
BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.
Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.
Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy.
PLoS ONE 01/2012; 7(6):e39409. · 4.09 Impact Factor
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ABSTRACT: The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved.
BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract.
Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum.
Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway inflammation in offspring by activating regulatory pathways, likely through TLR2/4 signalling.
PLoS ONE 01/2012; 7(7):e40271. · 4.09 Impact Factor
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ABSTRACT: The Indianmeal moth Plodia interpunctella is a highly prevalent food pest in human dwellings, and has been shown to contain a number of allergens. So far, only one of these, the arginine kinase (Plo i 1) has been identified.
The aim of this study was to identify further allergens and characterise these in comparison to Plo i 1.
A cDNA library from whole adult P. interpunctella was screened with the serum of a patient with indoor allergy and IgE to moths, and thioredoxin was identified as an IgE-binding protein. Recombinant thioredoxin was generated in E. coli, and tested together with Plo i 1 and whole moth extracts in IgE immunoblots against a large panel of indoor allergic patients' sera. BALB/c mice were immunised with recombinant thioredoxin and Plo i 1, and antibody production, mediator release from RBL cells, T-cell proliferation and cytokine production were measured.
For the first time a thioredoxin from an animal species was identified as allergen. About 8% of the sera from patients with IgE against moth extracts reacted with recombinant P. interpunctella thioredoxin, compared to 25% reacting with recombinant Plo i 1. In immunised BALB/c mice, the recombinant allergens both induced classical Th2-biased immune responses such as induction IgE and IgG1 antibodies, upregulation of IL-5 and IL-4 and basophil degranulation.
Thioredoxin from moths like Plo i 1 acts like a classical Type I allergen as do the thioredoxins from wheat or corn. This clearly supports the pan-allergen nature of thioredoxin. The designation Plo i 2 is suggested for the new P. interpunctella allergen.
PLoS ONE 01/2012; 7(7):e42026. · 4.09 Impact Factor
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ABSTRACT: Excepting tropical Africa, where Plasmodium falciparum prevails, Plasmodium vivax is the most frequent cause of malaria in Asia and Latin America. First reliable reports of chloroquine resistance came in 1989 from the area of the distribution of the Chesson-strain of P. vivax. Since then, reports also came from other areas of the world. This study had the objective of measuring the sensitivity of P.vivax to chloroquine and potential alternative compounds in western Thailand. The study was performed in 2008 in Mae Sot, Tak Province, and followed the method of Tasanor. The IC(50) and IC(90) values for chloroquine were 167 nM and 5445 nM, those for mefloquine were 139 nM and 5282 nM, those for artemisinin were 32 nM and 466 nM, and those for atovaquone 30 nM and 650 nM. The values for chloroquine indicate the existing or imminent occurrence of specific resistance. High prevalence of mefloquine resistance precludes its alternative use. However, atovaquone, in combination with proguanil, may be a possible alternative.
Wiener klinische Wochenschrift 09/2011; 123 Suppl 1:20-5. · 0.81 Impact Factor
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Eva Sallmann,
Bärbel Reininger,
Sabine Brandt,
Nikolaus Duschek,
Elisabeth Hoflehner,
Erika Garner-Spitzer,
Barbara Platzer,
Eleonora Dehlink,
Martina Hammer,
Martin Holcmann,
Hans C Oettgen, Ursula Wiedermann,
Maria Sibilia,
Edda Fiebiger,
Antal Rot,
Dieter Maurer
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ABSTRACT: The IgE-mediated and Th2-dependent late-phase reaction remains a mechanistically enigmatic and daunting element of human allergic inflammation. In this study, we uncover the FcεRI on dendritic cells (DCs) as a key in vivo component of this form of allergy. Because rodent, unlike human, DCs lack FcεRI, this mechanism could be revealed only by using a new transgenic mouse model with human-like FcεRI expression on DCs. In the presence of IgE and allergen, FcεRI(+) DCs instructed naive T cells to differentiate into Th2 cells in vitro and boosted allergen-specific Th2 responses and Th2-dependent eosinophilia at the site of allergen exposure in vivo. Thus, FcεRI on DCs drives the cascade of pathogenic reactions linking the initial allergen capture by IgE with subsequent Th2-dominated T cell responses and the development of late-phase allergic tissue inflammation.
The Journal of Immunology 07/2011; 187(1):164-71. · 5.79 Impact Factor
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Maria Paulke-Korinek,
Gustav Fischmeister,
Ana Grac,
Pamela Rendi-Wagner,
Michael Kundi,
Afsaneh Mohsenzadeh-Rabbani,
Katharina Moritz,
Beate Fenninger,
Reinhart Jarisch,
Joanna Jasinska,
Heidemarie Holzmann, Ursula Wiedermann,
Herwig Kollaritsch
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ABSTRACT: To determine the proficiency of the Austrian childhood vaccination schedule to induce long lasting seroprotection against vaccine preventable diseases a seroepidemiological study in 348 children between four and eight years of age was conducted. Antibodies against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps and rubella antigens were assessed in children, who had been vaccinated with hexavalent DTaP-HBV-IPV/Hib vaccines at three, four, five months and in the second year of life and/or MMR vaccines in the second year of life at least once, but mostly twice. High seroprotection rates (SPRs) were detected for tetanus (96%) and measles (90%). SPRs regarding diphtheria and mumps were 81% and 72%, respectively. Rubella-SPRs were 68% in females and 58% in males. Hepatitis B-antibody levels ≥10 mIU/mL were present in 52%; antibodies against pertussis were detected in 27% of the children. SPRs for measles and rubella depended on the interval since last vaccination; mumps-antibodies were significantly lower after one MMR-vaccination only. Antibodies against diphtheria, tetanus and pertussis depended on the interval since last vaccination while HBs-antibodies did not. The low levels of antibodies 1-7 years after vaccination against pertussis, rubella and mumps after only one vaccination should be considered when recommending new vaccination schedules.
Vaccine 05/2011; 29(32):5130-6. · 3.77 Impact Factor
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ABSTRACT: We compared the immunomodulatory properties of Bifidobacterium longum NCC 3001 and Lactobacillus paracasei NCC 2461 in a mouse model of poly-sensitization to birch and grass pollen allergens. Mucosal application of both strains at the time of sensitization and challenge led to significant suppression of airway inflammation and down-regulated allergen-specific immune responses. In contrast, in the mice treated with probiotics prior to sensitization and challenge, only B. longum displayed protective effects. Our findings stress that the choice of probiotic strain and the timing of the application are crucial for tolerance induction. Furthermore, this is the first demonstration of anti-allergic effects of probiotic bacteria in poly-sensitized mice.
Vaccine 02/2011; 29(10):1981-90. · 3.77 Impact Factor
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ABSTRACT: In consideration of comprehensive and well-established vaccination programmes in industrialized countries, it is expected that immunity against tetanus among expectant mothers and their offspring is complete. Our study evaluated seroprotection against tetanus among newborns in Austria, who may gain passive immunity by transplacental transfer of maternal tetanus antibody.
Cord blood samples from 99 deliveries were analyzed for antibody concentration against tetanus toxoid by standardized ELISA.
85/99 (85.8%) individuals presented with levels of tetanus immunity having a protective antibody concentration ≥0.1 IU/ml. 9/99 (9.1%) samples showed low seropositivity, while in 5/99 (5.1%) samples no tetanus antibodies could be detected. The median antibody concentration was 0.95 IU/ml.
Our data provide evidence for a lack of adequate tetanus immunity in 14.2% of newborns delivered in an Austrian University Hospital. This investigation is emphasizing the importance of stringent regimens concerning prenatal vaccination care, even in countries with generalized immunization programs. If indicated, maternal immunization during pregnancy should be initiated for protection of newborns.
Neonatology 01/2011; 100(1):52-6. · 2.66 Impact Factor
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ABSTRACT: The pharmacodynamic interaction between lumefantrine and monodesbutyl-benflumetol has been investigated in 44 fresh isolates of patients with a Plasmodium falciparum infection from the region of Mae Sot (Thailand). Both substances proved to be effective against parasite maturation within the test concentration range, with monodesbutyl-benflumetol being effective at a lower concentration than lumefantrine. Synergism between the two substances was evaluated with a combination of lumefantrine and monodesbutyl-benflumetol at a ratio of 4.25:1. The geometric mean values for complete inhibition of schizont maturation were 1035.7 nM for lumefantrine, 655 nM for monodesbutyl-benflumetol and 222.5 nM for the combination of both. An analysis for interaction according to the method of Berenbaum indicates a moderate synergism at the IC(50), which gets stronger with increasing ICs and reaches the highest level at the IC(99). The geometric mean of the sums of the FIC(50) is 0.73, of the FIC(90) it is 0.37 and of the FIC(99) it is 0.25.
Wiener klinische Wochenschrift 10/2010; 122 Suppl 3:61-5. · 0.81 Impact Factor
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ABSTRACT: Estimates of the annual number of infections with Plasmodium vivax reach 391 million. So far the blood-schizontocidal therapy with chloroquine remained effective in most parts of the world, but reports about emerging resistance are increasing. The study had the objective of determining the pharmacodynamic interaction between pyronaridine and retinol in Plasmodium vivax, since pyronaridine is a potential alternative for chloroquine and an earlier study had shown strong synergism between pyronaridine and retinol in Plasmodium falciparum. The study was conducted at the Malaria Clinic of Mae Sot, Tak Province, Thailand, near the border to Myanmar. The in vitro observations followed the method of Tasanor. Successful tests were performed with 44 isolates. The mean IC(50), IC(90) and IC(99) values for pyronaridine were 9.8, 2069.6 and 162446.5 nM. The mean IC(50), IC(90) and IC(99) values for the combinations with retinol (corresponding to the 50th, 65th and 80th percentile of the physiological retinol levels in healthy adults) were 1.7, 542.8 and 59379.5 nM for pyronaridine + retinol "low", for the combination with retinol "medium" they were 0.5, 313.7 and 58891.4 nM and for the combination with retinol "high" they were 0.2, 96.7 and 16754.3 nM. These results suggest strong synergism between the two substances.
Wiener klinische Wochenschrift 10/2010; 122 Suppl 3:66-70. · 0.81 Impact Factor
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ABSTRACT: Following the advent of mefloquine resistance in Plasmodium falciparum in Thailand in the 1990s, the combined treatment of falciparum malaria with artesunate and mefloquine was found to be highly effective in treating and curing the patients in the affected areas. Monitoring of the clinical-parasitological response and of the in vitro sensitivity of P. falciparum was systematically conducted in order to detect any signs of failure of this type of artemisinin-based combination treatment (ACT). In earlier observations the in vitro activity of artemisinin was found to be significantly enhanced when combined with retinol. The same applies to mefloquine. In order to check whether the synergism between artemisinin and mefloquine was maintained in the presence of retinol, the pharmacodynamic interaction of the three compounds was investigated in the western border area of Thailand. Successful parallel tests with mefloquine, artemisinin, retinol, mefloquine-artemisinin 5:1 as well as mefloquine-artemisinin (5:1) + retinol low, medium and high were obtained with 43 fresh parasite isolates. The retinol concentrations in the low, medium and high formulations corresponded to the 50th, 65th and 80th percentile of the physiological mean concentrations in the blood of healthy adults. The IC(50), IC(90) and IC(99) values for mefloquine alone showed a further increase over the data of 2008. In the combinations with artemisinin and retinol moderate synergism was observed at the IC(50), but synergism increased strongly at the IC(90) and the IC(99).
Wiener klinische Wochenschrift 10/2010; 122 Suppl 3:57-60. · 0.81 Impact Factor
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ABSTRACT: The increasing drug resistance of Plasmodium falciparum is a worldwide problem. The objective of the study was the assessment of the in vitro activity of artemisinin, mefloquine and quinine, in an area where P. falciparum is multi-drug resistant. The sensitivity tests were based on measuring the drug-dependent inhibition of schizont maturation. For the 43 successfully tested isolates the mean effective concentrations (IC(50) and IC(90)) for artemisinin were 0.0081 and 0.1372 μM, respectively. For mefloquine the IC(50) was 0.1260 μM and the IC(90) was 3.7345 μM. Quinine showed an IC(50) of 0.2155 μM and an IC(90) of 2.5040 μM. All tested drugs showed a significant reduction in the effectiveness, compared with the results of former years. This suggests a further rise of resistance of local P. falciparum, which is alarming especially for artemisinin and quinine.
Wiener klinische Wochenschrift 10/2010; 122 Suppl 3:52-6. · 0.81 Impact Factor
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Ursula Wiedermann
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ABSTRACT: The increase of TBE cases in Europe has become a problem of international public health and travel medicine, because it is not only of concern for endemic areas, but also for visitors from non-endemic countries. Although highly effective modern vaccines are on the market in 28 European countries, there are still 7, mainly Eastern European, countries with no or an uncertain number of cases and without licensed modern vaccines. The prevailing danger for travellers, however, lies in underestimation and not awareness of the disease by public authorities, travel agencies and by the travellers themselves, a lack of mandatory notifications and sometimes a lack of financial resources. Outside Europe TBE has mostly not been recognized as a travel associated disease. Recommendation for travellers to endemic countries and suggestions to extra-European travellers and health authorities as well as vaccination advices are summarized in this paper.
Travel Medicine and Infectious Disease 07/2010; 8(4):251-6. · 1.50 Impact Factor
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Ursula Wiedermann,
C Wiltschke,
J Jasinska,
M Kundi,
R Zurbriggen,
E Garner-Spitzer,
R Bartsch,
G Steger,
H Pehamberger,
O Scheiner,
C C Zielinski
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ABSTRACT: We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo. We have now finalized a phase I clinical trial with an anti-Her-2/neu vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides in patients with metastatic breast cancer (MBC). Ten MBC patients with low protein overexpression of Her-2/neu of MBC (+ or ++ upon immunohistochemistry, FISH negative) and positive hormone receptor status were enrolled in a single center phase I study. The virosomal formulated vaccine, consisting of 10 microg/peptide, was intramuscularly applied three times on days 1, 28, and 56. The primary endpoint of the study, which lasted 12 weeks, was safety, the secondary endpoint immunogenicity. Local erythema at the injection site was the only vaccine-related side effect occurring in four patients. In 8 of 10 patients an increase in peptide-specific antibody titer measured by ELISA was found. Importantly, the induced antibodies were also directed against the native Her-2/neu protein. Cellular immune responses, as measured by in vitro production of IL-2, IFN-c, and TNF-a of PBMCs showed a marked increase after vaccination in the majority of vaccinees. Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination. In all, the immunological responses after vaccination indicated that the patients in stage IV of disease were immunocompetent and susceptible to vaccination. The Her-2/neu multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance to Her-2/neu. The induction of anti-Her-2-specific antibodies could result in clinical benefit comparable to passive anti-Her-2 antibody therapy.
Breast Cancer Research and Treatment 02/2010; 119(3):673-83. · 4.43 Impact Factor
