| 1. |
- Björn, Camilla, et al.
(författare)
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Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r
- 2016
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 81, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing >= 99% of microorganisms in vitro, was in the range of 3-50 mu g/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-alpha) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 mu g/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. (C) 2016 Elsevier Inc. All rights reserved.
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| 2. |
- Ghirmai, Semhar, 1993, et al.
(författare)
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Relationship between hemolysis and lipid oxidation in red blood cell-spiked fish muscle; dependance on pH and blood plasma
- 2024
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between hemolysis and lipid oxidation was explored in red blood cell (RBCs)-spiked washed cod mince (WCM). At pH 6.8 and 3 ± 1 °C, intact RBCs (71 µM Hb) delayed lipid oxidation by 1 day compared to WCM with partly or fully lysed RBCs which oxidized immediately. Intact RBCs also lowered peak peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) with up to 59.5% and 48.1%, respectively. Adding 3% (v/w) blood plasma to RBC-spiked WCM delayed the lipid oxidation onset from 1 to 3–4 days without delaying hemolysis. At pH 6.4 the oxidation onset in RBC-WCM was the same as for pH 6.8 while at pH 7.2–7.6 lipid oxidation was suppressed for 7 days. Micrographs revealed RBC-lysis from day 2 at pH 6.4 but at pH 7.6, RBC stayed intact for ≥ 7 days. Thus, assuring presence of plasma-derived antioxidants and/or elevating muscle pH to avoid hemolysis can aid valorization of blood rich underutilized fish raw materials.
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| 3. |
- Chandolias, Konstantinos, et al.
(författare)
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Protective effect of a reverse membrane bioreactor against toluene and naphthalene in anaerobic digestion
- 2022
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Ingår i: Biotechnology and Applied Biochemistry. - : Wiley. - 1470-8744 .- 0885-4513. ; 69:3, s. 1267 -1274
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Tidskriftsartikel (refereegranskat)abstract
- Raw syngas contains tar contaminants including toluene and naphthalene, which inhibit its conversion to methane. Cell encasement in a hydrophilic reverse membrane bioreactor (RMBR) could protect the cells from hydrophobic contaminants. This study aimed to investigate the inhibition of toluene and naphthalene and the effect of using RMBR. In this work, toluene and naphthalene were added at concentrations of 0.5–1.0 and 0.1–0.2 g/L in batch operation. In continuous operation, concentration of 0–6.44 g/L for toluene and 0–1.28 g/L for naphthalene were studied. The results showed that no inhibition was observed in batch operation for toluene and naphthalene at concentrations up to 1 and 0.2 g/L, respectively. In continuous operation of free cell bioreactors (FCBRs), inhibition of toluene and naphthalene started at 2.05 and 0.63 g/L, respectively. When they were present simultaneously, inhibition of toluene and naphthalene occurred at concentrations of 3.14 and 0.63 g/L, respectively. In continuous RMBRs, no inhibition for toluene and less inhibition for naphthalene were observed, resulting in higher methane production from RMBR than that of FCBR. These results indicated that RMBR system gave a better protection effect against inhibitors compared with FCBR.
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| 4. |
- Rao, Komal Umashankar, et al.
(författare)
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A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.
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| 5. |
- Holmbäck, Jan, et al.
(författare)
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Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system
- 2022
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO (R)) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin (R) cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required.
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| 6. |
- Sieber, Arne Santa, et al.
(författare)
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Compact recreational rebreather with innovative gas sensing concept and low work of breathing design
- 2013
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Ingår i: Marine Technology Society journal. - : Marine Technology Society Inc.. - 0025-3324 .- 1948-1209. ; 47:6, s. 27-41
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Tidskriftsartikel (refereegranskat)abstract
- Recreational rebreathers are increasingly popular, and recreational diver training organizations now routinely offer training for rebreather diving. Few rebreathers on the market, however, fulfill the criteria of a dedicated recreational rebreather. These remain based on traditional sensor technology, which may be linked to rebreather use having an estimated 10 times the risk of mortality while diving compared with open circuit breathing systems. In the present work, a new recreational rebreather based on two innovative approaches is described. Firstly, the rebreather uses a novel sensor system including voltammetric and spectroscopic validation of galvanic pO2 sensor cells, a redundant optical pO2 sensor, and a two-wavelength infrared pCO2 sensor. Secondly, a new breathing loop design is introduced, which reduces failure points, improves work of breathing, and can be mass fabricated at a comparatively low cost. Two prototypes were assembled and tested in the laboratory at a notified body for personal protective equipment before both pool and sea water diving trials. Work of breathing was well below the maximum allowed by the European Normative. These trials also demonstrated that optical pO2 sensors can be successfully employed in rebreathers. The pCO2 sensor detected pCO2 from 0.0004 to 0.0024 bar. These new approaches, which include a new concept for simplified mechanical design as well as improved electronic control, may prove useful in future recreational diving apparatus.
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| 7. |
- Hederos, Carl-Axel, et al.
(författare)
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Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a questionnaire
- 2007
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 18:2, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological evaluations of the prevalence of asthma are usually based on written questionnaires (WQs) in combination with validation by clinical investigation. In the present investigation, we compared parental assessment of asthma among their preschool children in response to a WQ with the corresponding medical records in the same region. An International Study of Asthma and Allergies in Childhood (ISAAC)-based WQ was answered by 75% of the parents of 6295 children aged 1–6 yr. Clinically diagnosed asthma, recorded in connection with admissions to the hospital or a visit to any of the outpatient clinics in the same region, were analysed in parallel. Finally, a complementary WQ was sent to the parents of children identified as asthmatic by either or both of this approaches. In response to the WQ 5.9% were claimed to suffer from asthma diagnosed by a doctor. According to the medical records, the prevalence of clinically diagnosed asthma was 4.9%. The estimated prevalence among children requiring treatment for their asthma was 4.4%. The sensitivity of the WQ was 77%, the specificity 97.5%. In the 1–2 yr age group the sensitivity was only 22%. This WQ was able to identify 54% of the children with a medical record of asthma. Forty percent of the children claimed by their parents to be asthmatic had no medical record of asthma. An ISAAC-based parentally completed WQ provided an acceptable estimation of the prevalence of asthma in children 2–6 yr of age, although only half of the individual patients identified in this manner are the same as those identified clinically.
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| 8. |
- Karlsson, Hanna, et al.
(författare)
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Cell membrane damage and protein interaction induced by copper containing nanoparticles-Importance of the metal release process
- 2013
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 313:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- Cu-containing nanoparticles are used in various applications in order to e.g. achieve antimicrobial activities and to increase the conductivity of fluids and polymers. Several studies have reported on toxic effects of such particles but the mechanisms are not completely clear. The aim of this study was to investigate the interactions between cell membranes and well-characterized nanoparticles of CuO, Cu metal, a binary Cu-Zn alloy and micron-sized Cu metal particles. This was conducted via in vitro investigations of the effects of the nanoparticles on (i) cell membrane damage on lung epithelial cells (A549), (ii) membrane rupture of red blood cells (hemolysis), complemented by (iii) nanoparticle interaction studies with a model lipid membrane using quartz crystal microbalance with dissipation monitoring (QCM-D). The results revealed that nanoparticles of the Cu metal and the Cu-Zn alloy were both highly membrane damaging and caused a rapid (within 1 h) increase in membrane damage at a particle mass dose of 20 mu g/mL, whereas the CuO nanoparticles and the micron-sized Cu metal particles showed no such effect. At similar nanoparticle surface area doses, the nano and micron-sized Cu particles showed more similar effects. The commonly used LDH (lactate dehydrogenase) assay for analysis of membrane damage was found impossible to use due to nanoparticle-assay interactions. None of the particles induced any hemolytic effects on red blood cells when investigated up to high particle concentrations (1 mg/mL). However, both Cu and Cu-Zn nanopartides caused hemoglobin aggregation/precipitation, a process that would conceal a possible hemolytic effect. Studies on interactions between the nanoparticles and a model membrane using QCM-D indicated a small difference between the investigated particles. Results of this study suggest that the observed membrane damage is caused by the metal release process at the cell membrane surface and highlight differences in reactivity between metallic nanoparticles of Cu and Cu-Zn and nanoparticles of CuO.
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| 9. |
- Senek, Marina, et al.
(författare)
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Levodopa/carbidopa microtablets in Parkinson's disease : a study of pharmacokinetics and blinded motor assessment
- 2017
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Ingår i: European Journal of Clinical Pharmacology. - Heidelberg, Germany : Springer. - 0031-6970 .- 1432-1041 .- 0014-2999. ; 73:5, s. 563-571
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Tidskriftsartikel (refereegranskat)abstract
- Background: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.Objectives: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease.Methods: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.Results: AUC0–4/dose and Cmax/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).Conclusions: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
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| 10. |
- Leiva, Maria Carmen, et al.
(författare)
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
- 2021
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4709-4724
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.
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