Der Nachlass des Heimatschutzlandessatbsleiter von Oberösterreich Friedrich Mayer (1887 - 1937)

Archivmaterial über die Selbstschutzorganisation der „Heimwehr(en)“ ist sehr oft verschwunden oder vernichtet worden. Durch Zufall tauchte der Bestand der oberösterreichischen Landesleitung des Heimatschutzes auf, die unter der administrativen Leitung des Majors a.D. Friedrich Mayer (1887 – 1937) stand. Dieser Nachlass wurde von einem Bekannten des Autors erworben und dieser stellte ihn für die Bearbeitung dieser Arbeit zur Verfügung. Friedrich Mayer selbst, ein Offizier der k. u. k. Armee, dann bei der Volkswehr, wurde 1921 pensioniert. Danach organisierte er als Geschäftsführer („Landesstabsleiter“) den Aufbau der Heimwehren in Oberösterreich. Mayer betreute die Organisation in Oberösterreich als deren Geschäftsführer (auch unter der Führung des „Heimwehrfürsten“ Rüdiger Starhemberg) bis 1933 bevor er nach Wien wechselte. Nach politischer Aktivität im Ständestaat verstarb Major Mayer 1937 in Wien. Seine Hauptaufgaben als „Landesstabsleiter“ umfassten neben Organisation und Verwaltung der Selbstschutzorganisation auch den nachrichtendienstlichen Bereich (Überwachung von Gegnern des Heimwehr). Mit der Hilfe des Oberösterreichischen Landesarchivs konnte der Bestand von rund 5 Kartons gescannt werden. Er befand sich zu Beginn der Arbeit in dem Zustand, in dem er (vermutlich) 1937 nach Enns gebracht gewesen war. Die Akten wiesen durch Witterungseinflüsse und unsachgemäße Behandlung diverse Beschädigungen auf (u.a. Rostschäden durch Büroklammern und Metallklammern) und waren stark verschmutzt. Das gesamte Material umfasst die Zeit zwischen 1914 und 1941. Zuerst wurde der gesamte Bestand gescannt (300 dpI/ TIFF). Sodann erfolgte die Ordnung der Digitalisate in acht Untergruppen (A – H) nach dem Pertinenzprinzip („Betreffprinzip“). Innerhalb dieser Untergruppen existiert wieder eine Unterteilung – entweder zeitlich oder nach Organisationen. Dies betrifft vor allem den größten aller Teilbestände, den der Heimwehren. Eine Beschreibung der einzelnen acht Untergruppen erfolgt an typischen Beispielen aus dem Bestand. Das Dokument wird in einem Regest zusammengefasst, zum Teil ediert und die Besonderheiten beschrieben sowie in Vergleich mit der ganzen Untergruppe gestellt. Hauptbestandteil dieser Masterarbeit ist die Einzelaktenaufnahme des gesamten Bestandes. Jeder dieser Akte ist in einem Verzeichnis aufgenommen, die einzelnen Digitalisate sind mit einer Signatur versehen. Der Inhalt jedes einzelnen Stückes ist kurz gefasst beschrieben („Regest“). Von jedem einzelnen Akt wurden die topografischen Begriffe und die Eigennamen aller in ihnen vorkommenden Einzelpersonen extrahiert und in zwei Indices alphabetisch zusammengefasst (Personenindex, topografischer Index). Das Auffinden eines Einzelaktes erfolgt durch das Nachschlagen der Einzelsignaturen in den Indices. Die Originalakten des Nachlasses Mayer, der nach dem ISAD-G Standard geordnet wurde, liegen in einem Privatarchiv und sind nur in Ausnahmefällen einsehbar. Die Digitalisate des Nachlasses Friedrich Mayer sind am Oberösterreichischen Landesarchiv OÖLA gespeichert und dort einsehbar. Sie bilden einen wichtigen Bestandteil für die Aufarbeitung der Geschichte der Österreichischen Zwischenkriegszeit

Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection

The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza strains highlight the need for treatment alternatives. One such option is the creation of a protective physical barrier in the nasal cavity. In vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza A mouse infection model. Treatment of mice infected with a lethal dose of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours post infection resulted in a strong protection of mice similar to mice treated with oseltamivir. Since alternative treatment options for influenza are rare, we conclude that the nasal spray containing iota-carrageenan is an alternative to neuraminidase inhibitors and should be tested for prevention and treatment of influenza A in clinical trials in humans

Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials

&#x0D; &#x0D; &#x0D; &#x0D; Background: Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan.&#x0D; Methods: Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3–5 (visit 2).&#x0D; Results: Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p &lt; 0.05) as well as significantly fewer relapses during 21 days of observation period (p &lt; 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p &lt; 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p &lt; 0.01) and the number of relapses was three times less (p &lt; 0.01) in carrageenan treated corona-virus-infected patients compared to control patients.&#x0D; Conclusions: Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults.&#x0D; Trial registration: Pooled data from ISRCTN52519535 and ISRCTN80148028&#x0D; &#x0D; &#x0D; &#x0D; </jats:p

Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma

Accumulating evidence suggests the therapeutic potential of the immunosuppressive agent FTY720 (fingolimod) in hepatocellular carcinoma (HCC). Based on our previous finding that FTY720 mediates apoptosis in HCC cells by activating reactive oxygen species (ROS)-protein kinase C? (PKC?) signaling independent of effects on sphingosine-1-phosphate (S1P) receptors, we embarked on the pharmacological exploitation of FTY720 to develop a nonimmunosuppressive analogue with antitumor activity. This effort led to the development of OSU-2S, which exhibits higher potency than FTY720 in suppressing HCC cell growth through PKC? activation. In contrast to FTY720, OSU-2S was not phosphorylated by sphingosine kinase 2 (SphK2) in vitro, and did not cause S1P1 receptor internalization in HCC cells or T lymphocyte homing in immunocompetent mice. Although devoid of S1P1 receptor activity, OSU-2S exhibited higher in vitro antiproliferative efficacy relative to FTY720 against HCC cells without cytotoxicity in normal hepatocytes. Several lines of pharmacological and molecular genetic evidence indicate that ROS-PKC?-caspase-3 signaling underlies OSU-2S-mediated antitumor effects, and that differences in the antitumor activity between FTY720 and OSU-2S were attributable to SphK2-mediated phosphorylation of FTY720, which represents a metabolic inactivation of its antitumor activity. Finally, OSU-2S exhibited high in vivo potency in suppressing xenograft tumor growth in both ectopic and orthotopic models without overt toxicity. CONCLUSION: Using the molecular platform of FTY720, we developed OSU-2S, a novel PKC?-targeted antitumor agent, which is devoid of S1P1 receptor activity and is highly effective in suppressing HCC tumor growth in vivo. These findings suggest that OSU-2S has clinical value in therapeutic strategies for HCC and warrants continued investigation in this regard

Inhibitory effects of polysaccharide compounds.

<p>*Inhibitory concentration 50%: concentration in µg/ml required to inhibit influenza virus plaque formation on MDCK cells. Each value represents the mean of a quadruplicate assay.</p

Effect of iota-carrageenan on H1N1 virus adsorption and internalization.

<p>(A) Adsorption. H1N1 virus was added to MDCK cells in the presence of different concentrations of iota-carrageenan or control polymer carboxymethylcellulose (CMC). After viral adsorption for 1 h at 4°C, cells were washed and the number of cell-bound infectious viral particles determined by plaque assay; red bar 400 µg/ml, orange bar 4 µg/ml iota-carrageenan, black bar 400 µg/ml, grey bar 4 µg/ml CMC. (B) Adsorption/Internalization. H1N1 virus was added to MDCK cells and adsorbed for 1 h at 4°C. Cells were washed and allowed to internalize virus in the presence or absence of different concentrations of iota-carrageenan or CMC for 1 h at 37°C. Subsequently, internalized infectious viral particles were determined by plaque assay. (C) Immunofluorescent visualisation of virus adsorption in the presence of iota-carrageenan or CMC. 1 h post adsorption at 4°C, cells were stained after 1 h at 37°C with a mouse anti-NP antibody. (D) Adsorption/Internalization. H1N1 was added to MDCK cells and adsorbed for 1 h at 4°C. Cells were washed and allowed to internalize virus in the presence of iota-carrageenan or CMC for 1 h at 37°C. Compare the bright green stainings in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014320#pone-0014320-g005" target="_blank">Figure 5D</a> indicative of productive infection to 5C, where no green fluorescence is detected at high iota-carrageenan concentration.</p

Efficacy of iota-carrageenan in mice in comparison to oseltamivir.

<p>Ten mice per group were intranasally infected with 8.7×10³ PFU H1N1/PR/8/34 viral particles at day 0 and therapy started 48 h poi (blue indicates the placebo treatment). In addition to the group with intranasal treatment twice daily with 60 µg iota-carrageenan (green), a group of mice also received an oral dose of oseltamivir (10 mg/kg/day in 5% sucrose) (grey) twice daily for 5 days, and accordingly in combination with iota-carrageenan (red). P values were calculated by a Log-rank (Mantel-Cox) test. Survival was monitored daily for 15 days. Asterisk, p<0.05; triple asterisk p<0.001.</p

Binding of H1N1 influenza virus to iota-carrageenan.

<p>(A)-(F). Alexa Fluor 488-conjugated H1N1 influenza virus (H1N1-A488) was incubated with iota-carrageenan-coated agarose beads (iota-beads) or control beads for 30 min at room temperature and visualized microscopically. (A) Bright field picture of iota-beads, showing no green auto-fluorescence (B). (C) Control agarose beads incubated with H1N1-A488 do not facilitate unspecific virus binding. (D) Iota-beads incubated with H1N1-A488 demonstrates binding of virus to iota-carrageenan as evidenced by bright green staining of iota-beads. (E) Binding of H1N1-A488 to iota-beads is inhibited in the presence of iota-carrageenan (400 µg/ml), but is not abolished in the presence of CMC (400 µg/ml) (F). Scale bar  = 100 µm. (G) FACS analysis of MDCK cells incubated with H1N1-A488 in the presence of iota-carrageenan (400 µg/ml) (H) or control polymer CMC (400 µg/ml) (I) showing that binding of H1N1-A488 to cognate receptors is inhibited by iota-carrageenan but not CMC.</p

Effect of iota-carrageenan on pandemic H1N1/2009 virus.

<p>Confluent monolayers of MDCK cells in 6-well plates were washed free of protein-containing growth medium before use. An equal volume of virus suspension mixed with iota-carrageenan, containing 50 to 150 plaque-forming units, was added 5 to 10 min later, and plates were incubated at room temperature for 60 min with frequent shaking. The inoculum was removed and covered with an overlay medium consisting of 0.6% agarose (3 ml) in Eagle minimal essential medium and trypsin (2 µg/ml). Plates were incubated at 37°C in a humidified atmosphere with 5% CO₂. After 36 to 48 h, plaques were stained with crystal violet and counted. The percentage of plaque inhibition relative to infected control plates (y-axis) was determined for each drug concentration (x-axis). The standard deviation of three independent experiments is indicated.</p