| 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. |
- Dahlman-Höglund, Anna, 1964, et al.
(författare)
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Endotoxin in Size-Separated Metal Working Fluid Aerosol Particles
- 2016
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 60:7, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- Patients with airway symptoms working in metal working industries are increasing, despite efforts to improve the environmental air surrounding the machines. Our aim was to analyse the amount of endotoxin in size-separated airborne particles of metal working fluid (MWF) aerosol, by using the personal sampler Sioutas cascade impactor, to compare filter types, and to compare the concentration of airborne endotoxin to that of the corresponding MWFs. In a pilot field study, aerosols were collected in two separate machine halls on totally 10 occasions, using glass fibre and polytetrafluoroethylene (PTFE) filters in parallel at each station. Airborne endotoxin was distributed over all size fractions. While a major part was found in the largest size fraction (72%, 2.5-10 μm), up to 8% of the airborne endotoxin was detected in the smallest size fraction (<0.25 μm). Comparing the efficiency of the filter types, a significantly higher median endotoxin level was found with glass fibres filters collecting the largest particle-size fraction (1.2-fold) and with PTFE filters collecting the smallest ones (5-fold). The levels of endotoxin in the size-separated airborne particle fractions correlated to those of the MWFs supporting the aerosol-generating machines. Our study indicates that a significant part of inhalable aerosols of MWFs consists of endotoxin-containing particles below the size of intact bacteria, and thus small enough to readily reach the deepest part of the lung. Combined with other chemical irritants of the MWF, exposure to MWF aerosols containing endotoxin pose a risk to respiratory health problems. © 2016 The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.
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| 3. |
- Mattsby-Baltzer, Inger, 1949, et al.
(författare)
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IgG1 anti-cell wall and IgG2 anti-phosphopeptidomannan antibodies in the diagnosis of invasive candidiasis and heavy Candida colonization
- 2015
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Ingår i: Medical Mycology. - : Oxford University Press (OUP). - 1369-3786 .- 1460-2709. ; 53:7, s. 725-735
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a retrospective study to evaluate the usefulness of immunoglobulin G (IgG) subclasses against Candida cell wall fragments (CW) and phosphopeptidomannan (PPM) for the diagnosis of invasive candidiasis (IC). We analyzed 54 patients with IC (n = 19), Candida heavy colonization (HC; n = 16), and controls (no IC or HC, n = 19). In nonneutropenic patients (n = 47), the sensitivity and specificity values of IgG1 anti-CW and IgG2 anti-PPM in IC were 88%, 59%, and 88%, 94%, respectively. The areas under the receiver operating characteristic curves were 0.69 (0.51-0.88) and 0.901 (0.78-1.02), respectively. IgG1 mean values (arbitrary units) and 95% confidence interval were 46 (20-71), 42 (-0.38 to 84) and 20 (8.3-32) in IC, HC, and in controls, respectively, and discriminated IC but not HC from controls (P = .032, and P = .77, respectively). IgG2 mean values were 26 (9.2-42), 19 (4.4-33), and 3.2 (0.28-6.6) in IC, HC, and in controls, respectively, and discriminated both IC and HC from controls (P < .0001 and P = .035, respectively) but did not separate IC from HC (P = .2). IgG2 showed positivity as early as one day after the IC diagnosis. Antibodies were detected in only two out of a total of seven neutropenic patients. For both IC and HC patients, the diagnostic performance of IgG2 anti-PPM was better than the one of IgG1 anti-CW. In nonneutropenic patients, IgG2 anti-PPM accurately identified not only IC patients but also HC patients at high risk for IC. This marker may help clinicians in the initiation of early preemptive therapy.
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| 4. |
- Sargenti, Konstantina, et al.
(författare)
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Dysfunction of Circulating Polymorphonuclear Leukocytes and Monocytes in Ambulatory Cirrhotics Predicts Patient Outcome
- 2016
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 61:8, s. 2294-2302
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Tidskriftsartikel (refereegranskat)abstract
- Cirrhosis represents a state of functional immune paresis with increased infection risk. To investigate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics, and their potential relation with cirrhosis etiology or patient outcome. Consecutive ambulatory cirrhotics without current or recent (< 1 month) infection or acute decompensation were prospectively enrolled in 2013 and followed for a median time of 20 months until death, transplant or end of 2014. Oxidative burst and phagocytosis of circulating PMNs and monocytes were investigated at baseline and after in vitro Escherichia coli stimulation. Seventeen healthy blood donors served as controls. Baseline clinical and laboratory data as well as follow-up data on the development of cirrhosis complications, including acute-on-chronic liver failure (ACLF), and bacterial infections were collected. Sixty patients were included (70 % male, median age 63 years, 52 % with alcoholic cirrhosis). Compared to controls, cirrhotics showed increased resting and stimulated burst as well as reduced phagocytosis of PMNs, and increased stimulated monocyte burst (p < 0.05 for all). Alcoholic etiology was not related to PMN or monocyte dysfunction (p > 0.05 for all). In Cox regression analysis, increased stimulated monocyte and PMN burst were independent predictors of sepsis, severe sepsis and ACLF occurrence. Also, increased stimulated monocyte burst was associated with worse transplant-free survival (p < 0.05 for all). Stimulated PMN and monocyte oxidative burst are increased in ambulatory cirrhotics without acute decompensation. In turn, these changes are associated to sepsis and ACLF occurrence.
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