Artikler, rapporter og annet (farmasi)

Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

Evjen, Tove Julie — 2010-12-31T23:00:00Z

Evjen, Tove Julie; Brandl, Martin
Ultrasound sensitive (sonosensitive liposomes) are drug delivery systems designed for releasing their drug load upon exposure to ultrasound (US). Inclusion of dioleoylphosphatidylethanolamine (DOPE) in liposome membranes was previously shown to induce sonosensitivity. For efficient US mediated drug delivery to solid tumours, a long blood circulation time of the liposomal drug providing high tumour uptake is required. In this study, blood pharmacokinetics of DOPE-based liposomal doxorubicin (DXR) were evaluated in mice. A markedly faster blood clearance of DXR was observed for DOPE-rich liposomes compared to Caelyx! (standard liposomal DXR). Subsequently, liposome membrane composition was altered to improve drug retention in the bloodstream, while maintaining sonosensitivity. Formulations with reduced blood clearance of DXR were obtained by reducing the content of DOPE from 62 to 32 or 25 mol%. These formulations showed long blood circulation time, as approximately 20% of the administered DXR dose was present in the bloodstream 24 h after intravenous injection. The reduction in liposomal DOPE content did not significantly reduce US mediated DXR release in vitro, indicating that DOPE is a potent modulator to sonosensitivity. The novel liposome formulations, containing moderate amounts of DOPE, displayed similar blood pharmacokinetic profiles as standard liposomal DXR, but a markedly improved sonosensitivity.
This article is part of Tove Julie Evjens doctoral thesis. Available in Munin at http://hdl.handle.net/10037/3373

Characterization of the Ion Exchange Reaction Between Propranolol-H+ or K+ with Amberlite IRP 69 Resin by Both, Isothermal Titration Calorimetry and (Flame) Photometric Equilibrium Analysis

Zeiss, Daniel Horst — 2008-12-31T23:00:00Z

Zeiss, Daniel Horst; Wagner, Marita; Bauer-Brandl, Annette

The role of pharmacoepidemiological studies in the market withdrawal of carisoprodol (Somadril®) in Europe.

Skurtveit, Svetlana — 2007-12-31T23:00:00Z

Skurtveit, Svetlana; Bramness, Jørgen; Buajordet, Ingebjørg

A co-operative evaluation of different methods of detecting BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on second-line dasatinib or nilotinib therapy after failure of imatinib

Ernst, Thomas — 2008-12-31T23:00:00Z

Ernst, Thomas; Gruber, Franz; Pelz-Ackermann, Oliver; Mikkola, ingvild; Maier, J; Pfirrmann, M; Muller, MC; Porkka, Kimmo; Niederwieser, D; Hochhaus, A; Lange, T

Veitrafikkulykker knyttet til forskrivning av legemidler : En registerbasert kohortstudie

Skurtveit, Svetlana — 2007-12-31T23:00:00Z

Skurtveit, Svetlana; Engeland, Anders; Bramness, Jørgen G.; Mørland, Jørg

Repeated dispensing of codeine is associated with high consumption of benzodiazepines

Skurtveit, Svetlana — 2007-12-31T23:00:00Z

Skurtveit, Svetlana; Bachs, Liliana Casulleras; Bramness, Jørgen G.; Engeland, Anders

Signal transduction mechanisms involved in S100A4-induced activation of the transcription factor NF-kappa B

Mælandsmo, Gunhild — 2009-12-31T23:00:00Z

Mælandsmo, Gunhild; Grotterød, Ida; Pedersen, Kjetil Boye

Bacterial diversity in faeces from polar bear (Ursus maritimus) in Arctic Svalbard

Glad, Trine — 2009-12-31T23:00:00Z

Glad, Trine; Brusetti, Lorenzo; Aars, Jon; Bernhardsen, Pål; Nielsen, Kaare Magne; Andersen, Magnus; Sundset, Monica Alterskjær
Background Polar bears (Ursus maritimus) are major predators in the Arctic marine ecosystem, feeding mainly on seals, and living closely associated with sea ice. Little is known of their gut microbial ecology and the main purpose of this study was to investigate the microbial diversity in faeces of polar bears in Svalbard, Norway (74-81 degrees N, 10-33 degrees E). In addition the level of blaTEM alleles, encoding ampicillin resistance (ampr) were determined. In total, ten samples were collected from ten individual bears, rectum swabs from five individuals in 2004 and faeces samples from five individuals in 2006. Results A 16S rRNA gene clone library was constructed, and all sequences obtained from 161 clones showed affiliation with the phylum Firmicutes, with 160 sequences identified as Clostridiales and one sequence identified as unclassified Firmicutes. The majority of the sequences (70%) were affiliated with the genus Clostridium. Aerobic heterotrophic cell counts on chocolate agar ranged between 5.0 x 104 to 1.6 x 106 colony forming units (cfu)/ml for the rectum swabs and 4.0 x 103 to 1.0 x 105 cfu/g for the faeces samples. The proportion of ampr bacteria ranged from 0% to 44%. All of 144 randomly selected ampr isolates tested positive for enzymatic beta-lactamase activity. Three % of the ampr isolates from the rectal samples yielded positive results when screened for the presence of blaTEM genes by PCR. BlaTEM alleles were also detected by PCR in two out of three total faecal DNA samples from faeces three polar bears. Conclusion The bacterial diversity in faeces from polar bears in their natural environment in Svalbard is low compared to other animal species, with all obtained clones affiliating to Firmicutes. Furthermore, only low levels of blaTEM alleles were detected in contrast to their increasing prevalence in some clinical and commensal bacterial populations.

Screening for antibacterial and antifungal activities in marine benthic invertebrates from northern Norway

Tadesse, Margey — 2008-06-17T22:00:00Z

Tadesse, Margey; Gulliksen, Bjørn; Strøm, Morten B.; Styrvold, Olaf B.; Haug, Tor
Benthic marine invertebrates collected from sub-Arctic regions of northern Norway, were found to be a promising source of novel bioactive compounds against human and fish pathogenic bacteria and fungi. Lyophilized material from seven species of ascidians, six sponges and one soft alcyonid coral were extracted with 60% acidified acetonitrile (ACN). After separation into an ACN-rich phase (ACN extract) and an aqueous phase, and subsequent solid phase extraction of the aqueous phase, fractions differing in polarity were obtained and screened for antibacterial and antifungal activities, along with the more lipophilic ACN-extracts. Antimicrobial activity was determined against two Gram-negative, two Gram-positive bacteria, and two strains of fungi. Notably, all the invertebrate species in the study showed activity against all four strains of bacteria and the two strains of fungi. In general, the aqueous fractions displayed highest antimicrobial activity, and the most potent extracts were obtained from the colonial ascidian Synoicum pulmonaria which displayed activity against bacteria and fungi at a concentration of 0.02 mg/ml; the lowest concentration tested.
This is the accepted manuscript version of the article. Reprinted with permission. Published version is available at http://dx.doi.org/10.1016/j.jip.2008.06.009
The published version of this article is part of Margey Tasesse's doctoral thesis, which is available at http://hdl.handle.net/10037/2702

In vitro host range, multiplication and virion forms of recombinant viruses obtained from co-infection in vitro with a vaccinia-vectored influenza vaccine and a naturally occurring cowpox virus isolate

Okeke, Malachy Ifeanyi — 2009-05-11T22:00:00Z

Okeke, Malachy Ifeanyi; Tryland, Morten; Nilssen, Øivind; Moens, Ugo; Traavik, Terje
Background: Poxvirus-vectored vaccines against infectious diseases and cancer are currently under development. We hypothesized that the extensive use of poxvirus-vectored vaccine in future might result in co-infection and recombination between the vaccine virus and naturally occurring poxviruses, resulting in hybrid viruses with unpredictable characteristics. Previously, we confirmed that co-infecting in vitro a Modified vaccinia virus Ankara (MVA) strain engineered to express influenza virus haemagglutinin (HA) and nucleoprotein (NP) genes with a naturally occurring cowpox virus (CPXV-NOH1) resulted in recombinant progeny viruses (H Hansen, MI Okeke, Ø Nilssen, T Traavik, Vaccine 23: 499–506, 2004). In this study we analyzed the biological properties of parental and progeny hybrid viruses.
Results: Five CPXV/MVA progeny viruses were isolated based on plaque phenotype and the expression of influenza virus HA protein. Progeny hybrid viruses displayed in vitro cell line tropism of CPXV-NOH1, but not that of MVA. The HA transgene or its expression was lost on serial passage of transgenic viruses and the speed at which HA expression was lost varied with cell lines. The HA transgene in the progeny viruses or its expression was stable in African Green Monkey derived Vero cells but became unstable in rat derived IEC-6 cells. Hybrid viruses lacking the HA transgene have higher levels of virus multiplication in mammalian cell lines and produced more enveloped virions than the transgene positive progenitor virus strain. Analysis of the subcellular localization of the transgenic HA protein showed that neither virus strain nor cell line have effect on the subcellular targets of the HA protein. The influenza virus HA protein was targeted to enveloped virions, plasma membrane, Golgi apparatus and cytoplasmic vesicles.
Conclusion: Our results suggest that homologous recombination between poxvirus-vectored vaccine and naturally circulating poxviruses, genetic instability of the transgene, accumulation of non-transgene expressing vectors or hybrid virus progenies, as well as cell line/type specific selection against the transgene are potential complications that may result if poxvirus vectored vaccines are extensively used in animals and man.