1,721,011 research outputs found
Formulering og fremstilling av peptid- lignende antibiotika-holdige liposomer for levering mot bakterielle biofilmer
Full text linkNår bakterier vokser i form av biofilm er de beskyttet mot antibiotika, og i større grad resistent. Ved bruk av liposomer som et leveringssystem rettet mot biofilmer kan de gi en forbedret antimikrobiell effekt. Ladning på liposomene kan resultere i en forbedret interaksjon mellom liposomene og bakteriecelleoverflaten. Dette kan forbedre penetrasjonen av biofilmen hvor bakterier sitter i og under en matrix av ekstracellulære materiale.
I denne masteroppgaven ble en nøytral hovedlipid, DPPC, kombinert med enten positiv ladet DPTAP eller negativ ladet DPPG i ulik molforhold. Totalt ble det prøvd å produsere fire ulike liposomformuleringer og en passende fremstillingsmetode ble etablert. Enkelte formuleringer som DPPC/ 10% DPTAP og DPPC/ 2.5% DPPG viste dårlig stabilitet fra første måling av deres egenskaper. Dermed ble disse to formuleringene utelukket som kandidater for innkapsling av ulike peptidbaserte antibiotika (polymyxin B, gentamicin og bacitracin). DPPC/ 10% DPPG viste seg å være en dårlig formulering for innkapsling av de ulike antibiotikaene. Alle formuleringene viste dårlig stabilitet ved karakterisering etter fremstilling med forhøyet zeta-average samt en størrelsesfordeling (ved intensitet) med flere topper. DPPC/ 2.5% DPTAP var den eneste formulering som hadde ønskede egenskaper etter produksjonen.
De mikrobiologiske testene på planktoniske celler ble gjennomført ved bruk av to ulike bakterier; P. aeruginosa (DSM22644) og S. aureus (DIM2569). Testing på planktoniske tester ble gjennomført ved måling av absorbansen ved bruk av en plateleser. Volum til og med 1.25 μL ga ingen vekstrespons. Resultatene viser også at veksthemingen var stabil over testperioden på 12 timer. Dette indikerer at DPPC/ 2.5% DPTAP frigjører minst MIC under hele analyse tidsperioden.
De mikrobiologiske testene på biofilm ble gjort på to ulike metoder for P. aeruginosa og S. aureus. P. aeruginosa biofilm ble etablert i 96-brønnplater av plast og ble behandlet med mindre liposomvolum. Her var det dårlig hemming av allerede etablert biofilm. S. aureus biofilm ble etablert på kammerobjektglass og ble behandlet med større liposomvolum. Resultatene fra testen mot S. aureus biofilm antyder at allerede bruk av 100 μL av liposomformuleringen gir en svak hemming av biofilmer. CFU/mL for 100 μL ble beregnet til 3.31818 x 104, 1000 μL til 8.7 x 104 og 2000 μL kontra CFU/mL på 4.22523 x 108 for bakterier som ble ikke utsatt for DPPC/ 2.5% DPTAP med innkapslet gentamicin.When bacteria grow in biofilms, they are protected from antibiotics and are to a greater extent resistant. By using liposomes as a drug delivery system directly aimed at biofilms it can enhance the antimicrobial effect. Charged liposomes can increase the interaction between the liposomes and the bacterial cell surface. This can improve the penetration of the biofilm where bacteria are in and under a matrix of extracellular material
In this study a neutral lipid, DPPC, was combined with either a positively charged lipid, DPTAP, or negatively charged lipid, DPPG, in different molar ratios. In total, four different liposome formulations were made, and a suitable preparation method was established. Some formulations such as DPPC/ 10% DPTAP and DPPC/ 2.5% DPPG showed poor stability; thus, these two formulations were excluded as candidates for encapsulation of peptide-based antibiotics (polymyxin B, gentamicin and bacitracin). DPPC/ 10% DPPG was not suitable for encapsulation of the different antibiotics; the formulation showed poor stability with an elevated zeta-average and a size distribution with several peaks. Only gentamicin encapsulated in DPPC/ 2.5% DPTAP had the desired properties post-production. During storage there was a change in the zeta potential, but this formulation was nevertheless used for the microbiological tests.
P. aeruginosa (DSM22644) and S. aureus (DIM2569) was used for the microbiological tests. The first test was conducted on agar plates. Testing on planktonic cells was done by measuring the absorbance of the cells using a plate reader. A minimum volume of μL gave no bacterial growth response. The results from this test shows that growth inhibition was stable over the 12-hour test period. This indicated that DPPC/ 2.5% DPTAP release at least MIC during the entire analysis.
The tests on P. aeruginosa and S. aureus biofilms was conducted in two different manners. P. aeruginosa biofilm was grown in a 96-well plastic plate and was treated with lower liposomal gentamicin volume and there was poor inhibition of the already established biofilm. S. aureus biofilm was grown in 1-well chamber slides and treated with higher volume of the liposome gentamicin suspension. The results from the test against S. aureus biofilm suggested that a volume of as low as 100 μL of liposomal gentamicin gives an inhibition. CFU /mL for 100 mL was calculated to 3.31818 x 104 CFU/mL, 1000 μL to 8.7 x 104 CFU/mL and 2000 μL versus CFU /mL of 4.22523 x 108 for bacteria not exposed to DPPC / 2.5% DPTAP with encapsulated gentamicin
Characterization of mold in indoor air and development of respiratory illness : developing co-culture techniques to reveal how fungal conidia in Norwegian indoor air might cause respiratory health problems
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Characterization of mold in indoor air and development of respiratory illness : developing co-culture techniques to reveal how fungal conidia in Norwegian indoor air might cause respiratory health problems
Full text linkMaster i biomedisi
Formulering og fremstilling av peptid- lignende antibiotika-holdige liposomer for levering mot bakterielle biofilmer
No full textNår bakterier vokser i form av biofilm er de beskyttet mot antibiotika, og i større grad resistent. Ved bruk av liposomer som et leveringssystem rettet mot biofilmer kan de gi en forbedret antimikrobiell effekt. Ladning på liposomene kan resultere i en forbedret interaksjon mellom liposomene og bakteriecelleoverflaten. Dette kan forbedre penetrasjonen av biofilmen hvor bakterier sitter i og under en matrix av ekstracellulære materiale.
I denne masteroppgaven ble en nøytral hovedlipid, DPPC, kombinert med enten positiv ladet DPTAP eller negativ ladet DPPG i ulik molforhold. Totalt ble det prøvd å produsere fire ulike liposomformuleringer og en passende fremstillingsmetode ble etablert. Enkelte formuleringer som DPPC/ 10% DPTAP og DPPC/ 2.5% DPPG viste dårlig stabilitet fra første måling av deres egenskaper. Dermed ble disse to formuleringene utelukket som kandidater for innkapsling av ulike peptidbaserte antibiotika (polymyxin B, gentamicin og bacitracin). DPPC/ 10% DPPG viste seg å være en dårlig formulering for innkapsling av de ulike antibiotikaene. Alle formuleringene viste dårlig stabilitet ved karakterisering etter fremstilling med forhøyet zeta-average samt en størrelsesfordeling (ved intensitet) med flere topper. DPPC/ 2.5% DPTAP var den eneste formulering som hadde ønskede egenskaper etter produksjonen.
De mikrobiologiske testene på planktoniske celler ble gjennomført ved bruk av to ulike bakterier; P. aeruginosa (DSM22644) og S. aureus (DIM2569). Testing på planktoniske tester ble gjennomført ved måling av absorbansen ved bruk av en plateleser. Volum til og med 1.25 μL ga ingen vekstrespons. Resultatene viser også at veksthemingen var stabil over testperioden på 12 timer. Dette indikerer at DPPC/ 2.5% DPTAP frigjører minst MIC under hele analyse tidsperioden.
De mikrobiologiske testene på biofilm ble gjort på to ulike metoder for P. aeruginosa og S. aureus. P. aeruginosa biofilm ble etablert i 96-brønnplater av plast og ble behandlet med mindre liposomvolum. Her var det dårlig hemming av allerede etablert biofilm. S. aureus biofilm ble etablert på kammerobjektglass og ble behandlet med større liposomvolum. Resultatene fra testen mot S. aureus biofilm antyder at allerede bruk av 100 μL av liposomformuleringen gir en svak hemming av biofilmer. CFU/mL for 100 μL ble beregnet til 3.31818 x 104, 1000 μL til 8.7 x 104 og 2000 μL kontra CFU/mL på 4.22523 x 108 for bakterier som ble ikke utsatt for DPPC/ 2.5% DPTAP med innkapslet gentamicin
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Quantification and identification of microplastics and heavy metals in restored and natural soil - environmental and human risk assessments
Full text linkBackground: Plastic pollution is a pressing concern with global plastic waste expected to increase in the coming years. Microplastics (MPs), measuring <5 mm in diameter, infiltrate aquatic, terrestrial and air environments. MPs can be primary (e.g microbeads in cosmetics, fibre discharge from textiles) or secondary (from the breakdown of larger plastics). Heavy metals (HMs) are toxic pollutants that stem from natural sources like volcanic eruption or anthropogenic sources like industrial activity. Both MPs and HMs can cause histopathological damage and inflammation in humans and tend to accumulate in the environment due to their non-degradable nature and long-range transport capacity. Using sewage sludge (SS) from municipal wastewater treatment plant (WWTP) as soil amendment, may be an entry pathway for MPs and HMs into the environment. MPs and HMs can have detrimental effects in soil, affecting various factors like soil quality, vegetation growth, soil flora and fauna.
Aim: To quantify and identify MPs and HMs in soil, and to assess their associated human and environmental risks.
Material and methods: A total of 18 soil samples were collected from a quarry restoration in Alcover, Spain, with SS amendment (AL-F), without SS (AL-T), and a nearby forest (AL-BO), across different soil horizons (A, A/C, C). MP analysis involved ZnCl2 density separation and Fenton oxidation, before being examined under the microscope (50x) and eventually analysed with FT-IR-spectroscopy. For HM analysis, microwave-assisted acid extraction was done (EPA method nr. 3051A), following analysis with inductively coupled plasma mass spectrometry (ICP-MS) or -atomic emission spectrometry (ICP-AES).
Results: AL-F soil contained an average of 1600 MPs/kg dw, compared to 123 MPs/kg in AL-T and 40 MPs/kg in AL-BOB. Polyester fibre was the most prevalent polymer type. Excessive Zn- (146.5; 140.3; 116.1 mg/kg) and Pb-values (119.8 mg/kg) were observed in Technosol with sludge, exceeding the Catalonian reference value for the ecosystem and human health protection, with a significant difference in Zn concentrations (p = 0.04)
Conclusion: Soil amended with SS showed significantly higher concentrations of MPs and HMs, indicating a potential threat to the soil, surrounding environment, and can affect human health. However, the bioavailability of HMs in soil is deemed low, suggesting a reduced risk of leaching and of affecting the soil ecosystem and humans. Considering that the soil stems from a quarry and not agricultural farmland, the chances of reaching humans is likely low. The persistence of MPs and HMs in soil even after 27 years underscores the importance of monitoring their levels in SS used as soil amendment due to their environmental impact
Pharmacological Evaluation of Newly Synthesized Compounds for the Treatment of Glioblastoma In vitro testing of new NBDHEX-derivatives
Full text linkGlioblastoma (GBM) is the most aggressive and common malignant brain tumour in adults, characterized by a poor overall survival rate of 12-15 months and limited treatment options. The standard treatment protocol involves maximal safe tumour resection followed by concomitant and adjuvant chemotherapy with temozolomide (TMZ), a DNA alkylating agent. Overexpression of the detoxifying enzyme Glutathione S-Transferase Pi 1-1 (GSTP1-1) in GBM correlates with poorer outcomes and increased treatment resistance by regulating cellular redox balance and inhibiting apoptosis through interaction with c-Jun N-terminal kinase (JNK). Although 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), a known GSTP1-1 inhibitor, has shown efficacy against GBM in vitro and in vivo, it exhibits non-specificity and metabolic instability. In recent years, a variety of derivatives have been synthesized.
We synthesized 14 NBDHEX-derivatives and identified two promising candidates for further evaluation. These compounds were tested on GBM cell lines U87MG and T98G, assessing cytotoxicity, mechanism of action, and potential synergy with TMZ via several assays, including trypan blue exclusion, resazurin reduction, sulforhodamine B colorimetric, immunoblotting, spheroid growth, and wound healing. The cytotoxic effects of the compounds were further assessed on patient-derived GBM cells.
Both compounds reduced cell viability of both the continuous cell lines and the patient-derived, with IC50 values at micromolar concentrations. Both compounds showed synergy with TMZ in U87MG, whereas only MC4936 demonstrated synergy in T98G. The pan-caspase inhibitor zVad-FMK did not rescue the cells, and minimal, dose-dependent PARP-1 cleavage was observed, contrasting with previous literature regarding NBDHEX and its derivatives. Pertinently, NAC consistently rescued cells from both compounds in both cell lines in the resazurin-based assays, aligning with the role GSTP1-1 plays in cellular processes, although the SRB results were inconsistent. In U87MG, ferroptosis-inhibitors Ferrostatin-1 and deferoxamine (DFO) restored some cell viability in MC4937-treated cells, and overexpression of the ferroptosis-associated protein acyl-CoA synthetase long-chain family member 4 (ACSL4) was observed. In T98G, DFO improved cell viability in MC4936-treated cells. Neither compound affected spheroid growth nor showed synergy, but both modestly reduced T98G wound healing, with slight synergy observed.
In conclusion, both compounds exhibit strong in vitro efficacy and synergy with TMZ, with MC4937 demonstrating a slightly higher efficacy. Consistent with the mechanism of GSTP1-1, the inhibitors appear to induce ROS, but, unexpectedly, not apoptosis. There is an indication that ferroptosis may be involved; however, the results remain inconclusive. To confirm and elucidate our findings, immunoblotting of key proteins such as caspase-3 and Glutathione Peroxidase 4 (GPX4) is necessary, along with conducting several biological replicates to validate our results. Nonetheless, both compounds exhibit efficacy in GBM cells and synergy with TMZ, warranting further in vitro and in vivo investigation
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