| 1. |
- Abu-Humaidan, Anas, et al.
(författare)
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The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation.
- 2014
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 192:7, s. 3355-3364
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement components in keratinocytes and epidermis following stimulation with proinflammatory cytokines. Importantly, EGFR inhibition of cultured keratinocytes either alone or in combination with proinflammatory stimulus promoted activation of the complement system after incubation with serum. In keratinocytes treated solely with the EGFR inhibitor, complement activation was dependent on serum-derived C1q, whereas in keratinocytes stimulated with a combination of proinflammatory cytokines and EGFR inhibition, complement activation was found even with C1q-depleted serum. In contrast to human keratinocytes, EGFR inhibition did not enhance complement component expression or cause complement activation in murine keratinocytes. These data demonstrate an important role for EGFR in regulating the expression of complement components and complement activation in human epidermis and keratinocytes and, to our knowledge, identify for the first time a pathway important for the epidermal regulation of complement activation.
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| 2. |
- Emanuelsson, Andreas, et al.
(författare)
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Accounting for overfishing in life cycle assessment: new impact categories for biotic resource use
- 2014
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Ingår i: International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 19:5, s. 1156-1168
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Tidskriftsartikel (refereegranskat)abstract
- Overfishing is a relevant issue to include in all life cycle assessments (LCAs) involving wild caught fish, as overfishing of fish stocks clearly targets the LCA safeguard objects of natural resources and natural ecosystems. Yet no robust method for assessing overfishing has been available. We propose lost potential yield (LPY) as a midpoint impact category to quantify overfishing, comparing the outcome of current with target fisheries management. This category primarily reflects the impact on biotic resource availability, but also serves as a proxy for ecosystem impacts within each stock. LPY represents average lost catches owing to ongoing overfishing, assessed by simplified biomass projections covering different fishing mortality scenarios. It is based on the maximum sustainable yield concept and complemented by two alternative methods, overfishing though fishing mortality (OF) and overfishedness of biomass (OB), that are less data-demanding. Characterization factors are provided for 31 European commercial fish stocks in 2010, representing 74 % of European and 7 % of global landings. However, large spatial and temporal variations were observed, requiring novel approaches for the LCA practitioner. The methodology is considered compliant with the International Reference Life Cycle Data System (ILCD) standard in most relevant aspects, although harmonization through normalization and endpoint characterization is only briefly discussed. Seafood LCAs including any of the three approaches can be a powerful communicative tool for the food industry, seafood certification programmes, and for fisheries management.
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| 3. |
- Gauffin, Håkan, et al.
(författare)
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Knee arthroscopic surgery is beneficial to middle-aged patients with meniscal symptoms: a prospective, randomised, single-blinded study
- 2014
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 22:11, s. 1808-1816
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. Method: 150 out of 179 eligible patients, aged 45 to 64 (mean: 54 +/- 5), symptom duration more than 3 months and standing X-ray with Ahlback grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). Results: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. Conclusion: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didnt affect the outcome.
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| 4. |
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| 5. |
- Nilsson, Andreas, et al.
(författare)
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Difficulties in Controlling Mobilization Pain Using a Standardized Patient-Controlled Analgesia Protocol in Burns
- 2011
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Ingår i: JOURNAL OF BURN CARE and RESEARCH. - : Lippincott Williams andamp; Wilkins. - 1559-047X. ; 32:1, s. 166-171
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate pain relief for patients with burns during rest and mobilization with morphine according to a standard protocol for patient-controlled analgesia (PCA). Eighteen patients with a mean (SD) burned TBSA% of 26 (20) were studied for 10 days. Using a numeric rating scale (NRS, 0 = no pain and 10 = unbearable pain), patients were asked to estimate their acceptable and worst experienced pain by specifying a number on a scale and at what point they would like additional analgesics. Patients were allowed free access to morphine with a PCA pump device. Bolus doses were set according to age, (100 - age)/24 = bolus dose (mg), and 6 minutes lockout time. Degrees of pain, morphine requirements, doses delivered and demanded, oral intake of food, and antiemetics given were used as endpoints. Acceptable pain (mean [SD]) was estimated to be 3.8 (1.3) on the NRS, and additional treatment was considered necessary at scores of 4.3 (1.6) or more. NRS at rest was 2.7 (2.2) and during mobilization 4.7 (2.6). Required mean morphine per day was 81 (15) mg, and the number of doses requested increased during the first 6 days after the burn. The authors found no correlation between dose of morphine required and any other variables. Background pain can be controlled adequately with a standard PCA protocol. During mobilization, the pain experienced was too intense, despite having the already high doses of morphine increased. The present protocol must be refined further to provide analgesia adequate to cover mobilization as well.
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| 6. |
- Nordin, Sara, et al.
(författare)
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The epithelium-produced growth factor midkine has fungicidal properties
- 2012
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 67:8, s. 1927-1936
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESThe skin encounters many potential pathogens present in the environment, where Candida spp. are among the most common causes of fungal infestation. Midkine (MK) is a heparin-binding growth factor that is constitutively produced in the epidermis and this study looks at the antifungal activity of MK, potential co-localization and mode of action of MK.METHODS AND RESULTSWe show that MK is expressed in association with fungal infections of the skin. In vitro, MK showed strong fungicidal activity against Candida albicans and Candida parapsilosis. Scanning electron microscopy of fungi revealed blebbing and leakage of intracellular contents, indicating membrane interactions. Immunoelectron microscopy showed accumulation of MK in association with the membrane, but also a high degree of internalization, suggesting intracellular targets as well. Using liposome models mimicking fungal and human cell membranes (i.e. ergosterol- and cholesterol-containing membranes, respectively), MK was found to disrupt ergosterol-containing membranes to a higher degree than cholesterol-containing vesicles. Addition of increasing concentrations of salt caused a partial and dose-dependent decrease in the fungicidal activity exerted by MK in parallel with a decreased affinity for the yeast. However, at salt concentrations similar to those of an epithelial context (i.e. 50-100 mM), MK retained most of its fungicidal activity, in contrast to that of plasma (150 mM).CONCLUSIONSThe findings suggest that MK plays a role in host defence against fungal infections and could serve as a template for development of novel antifungal treatments.
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| 7. |
- Saleh, Karim, et al.
(författare)
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A Descriptive Study of Bacterial Load of Full-Thickness Surgical Wounds in Dermatologic Surgery.
- 2011
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Ingår i: Dermatologic Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4725 .- 1076-0512. ; 37, s. 1014-1022
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Surgical site infections (SSIs) after dermatologic surgery cause pain, prolong healing, result in unaesthetic complications, and lead to excessive use of antibiotics. The pathogenesis of wound infections is complex and is dependent on bacterial load and diversity, among several factors. OBJECTIVE To investigate bacterial dynamics at dermatosurgical sites at different time intervals and assess the correlation with postoperative outcomes and to examine different endo- and exogenous factors that may contribute to SSIs. METHODS Eighteen patients undergoing skin grafting of the face were studied. The following SSI-related factors were registered: age and sex of the patient, ulceration of the lesion, diabetes, immunosuppressive therapy, smoking, anticoagulative therapy, and use of antibiotic prophylaxis. Wounds from each patient were swabbed preoperatively, intraoperatively, and postoperatively. The bacterial composition of the swabs was then analyzed quantitatively and qualitatively. RESULTS Sixteen of 18 surgical sites contained varying quantities of surface-associated bacteria. Coagulase-negative staphylococci and Propionibacterium acnes were the predominant bacteria isolated at all times. Intraoperative analysis was not predictive of SSIs. Use of antibiotic prophylaxis was the only registered SSI-related factor that showed significant variation in bacterial load between pre- and postoperative samples. Postoperative bacterial load was found to be lower than preoperative load in patients who received antibiotics. This was in contrast to patients who did not receive antibiotics, who had significantly higher postoperative levels (p=.02). The presence of high postoperative bacterial loads, regardless of the bacterial species isolated, showed a statistically significant positive correlation with a complicated postoperative outcome (p≤.001). CONCLUSIONS This study provides novel insights into the bacterial dynamics of dermatologic surgery-induced wounds and the variation of this over time. The results highlight the potential relevance of quantifying bacterial loads, as well as determining specific types of bacteria, in dermatologic surgery. The authors have indicated no significant interest with commercial supporters.
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| 8. |
- Sonesson, Andreas, et al.
(författare)
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Antifungal activities of peptides derived from domain 5 of high-molecular-weight kininogen.
- 2011
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Ingår i: International Journal of Peptides. - : Hindawi Limited. - 1687-9775 .- 1687-9767. ; 2011:Sep 14
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Tidskriftsartikel (refereegranskat)abstract
- In both immunocompromised and immunocompetent patients, Candida and Malassezia are causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind to Candida and other pathogens, leading to activation of the contact system. A cutaneous Candida infection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killed Candida and Malassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His(479)-His(498)), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity.
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| 9. |
- Sonesson, Andreas
(författare)
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Aspects of Microbial Influence on Skin Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The skin constitutes an effective barrier mediating protection against environmental danger and foreign substances. At the surface of the skin, the residential microorganisms grow as small colonies and consist of various non-pathogenic bacteria, fungi and viruses. However, the cutis is also exposed to pathogenic microorganisms, and to combat this threat the residential cells of the epidermis have evolved several mechanisms to prevent infection. One of the primary strategies used by epidermal cells is secretion of antimicrobial peptides (AMPs). AMPs are small cationic peptides, 20 to 60 amino acids in length, with the capacity to kill microorganisms. Individuals with atopic dermatitis (AD), a chronic inflammatory skin disease characterized by a defective epidermal barrier and abnormalities in the innate and adaptive immune systems, are highly predisposed to colonization and penetration of the skin by pathogenic microorganisms and their allergens. The results presented in this thesis indicate that IgE sensitization to skin-associated microbial antigens in patients with AD has an impact on disease severity. Furthermore, we showed that glycosaminoglycans (GAGs), inhibit the antibacterial activity of LL-37 in biological fluids. In paper III, the fungus Candida was found to induce complement degradation, leading to the generation of C3a. In addition, C3a and C3a-derived peptides demonstrated antifungal activities. By modifications of the net charge, hydrophobicity, as well as helical propensity of C3a-derived peptides, it was possible to enhance the antifungal activities of peptides. Thymic stromal lymphopoietin (TSLP) is a cytokine expressed by epithelial cells and of importance in AD. Novel antimicrobial activity, preferentially against Gram-negative bacteria, was discovered for TSLP. TSLP was degraded into low-molecular weight fragments by proteases derived from skin-associated pathogens, as well as human neutrophil elastase. Microbial pathogens and their products play an influential role and are potential triggers for the maintenance of the inflammatory processes in skin diseases such as AD. Knowledge of interactions between components of host defense and microbial pathogens can potentially facilitate development of strategies to control the microbial impact in skin infection and inflammation.
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| 10. |
- Sonesson, Annika, et al.
(författare)
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Determination of serum amyloid P component in seminal plasma and correlations with serum hormone levels in young, healthy men.
- 2011
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:7, s. 569-575
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Serum amyloid P component (SAP) belongs to the pentraxin family of proteins. SAP is evolutionary conserved, and involved in amyloidosis, innate immunity, inflammation, and apoptosis. We have previously described SAP in the male reproductive tract, where it occurs in seminal fluid, on spermatozoa, and in epididymal, seminal vesicle, and prostate tissue. In the present investigation, our aim was to characterize SAP in male reproduction. In short, we developed and evaluated an immunoassay, analysed the concentration of SAP in seminal plasma and serum in samples from healthy men (N = 203), and studied hormonal regulation. SAP in seminal plasma showed a positively skewed distribution and a median concentration of 1.01 mg/L (inter quartile range [IQR] 0.56-1.65 mg/L). SAP in serum had a Gaussian distribution and a median concentration of 40.5 mg/L (IQR 34.2-49.2 mg/L). Furthermore, SAP concentrations in seminal plasma were not correlated with serum concentrations of SAP, testosterone, sex hormone-binding globulin (SHBG), the testosterone/SHBG ratio, inhibin B, or estradiol. Only a weak negative correlation was found between seminal plasma SAP and serum levels of follicle-stimulating hormone (FSH) (Spearman's rho -0.159; p = 0.023) and luteinizing hormone (LH) (Spearman's rho -0.162; p = 0.021). In conclusion, all men investigated had measurable SAP levels in seminal plasma and in serum. SAP concentrations were 40 times lower in seminal fluid than in serum, and there was no correlation between those two variables. It seems that hormonal regulation is not the major pathway regulating seminal plasma SAP, and seminal plasma SAP and serum SAP are not co-regulated.
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