| 1. |
- Angelin, Martin, et al.
(författare)
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Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad : A prospective study
- 2015
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Ingår i: Travel Medicine and Infectious Disease. - : Elsevier BV. - 1477-8939 .- 1873-0442. ; 13:3, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: The increase of antibiotic resistance in clinically important bacteria is a worldwide threat, especially in healthcare environments. International travel is a risk factor for gut colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare students of being colonized with ESBL-PE when participating in patient-related work abroad has not been previously investigated. Methods: Swedish healthcare students travelling for pre-clinical and clinical courses outside Scandinavia submitted faecal samples and survey data before and after travel. The faecal samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae (CPE). Screening results and survey data were analysed to identify risk factors for colonization. Results: In the 99 subjects who submitted a full set of samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was found. The most important risk factor for ESBL-PE colonization was travel destination, and the highest colonization rate was found in the South East Asia region. Antibiotic treatment during travel was an independent risk factor for ESBL-PE colonization but patient-related work was not significantly associated with an increased risk. Conclusions: Patient-related work abroad was not a risk factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre-travel advice on avoiding unnecessary antibiotic treatment during travel is recommended.
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| 2. |
- Forsell, Joakim, et al.
(författare)
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The relation between Blastocystis and the intestinal microbiota in Swedish travellers
- 2017
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blastocystis sp. is a unicellular eukaryote that is commonly found in the human intestine. Its ability to cause disease is debated and a subject for ongoing research. In this study, faecal samples from 35 Swedish university students were examined through shotgun metagenomics before and after travel to the Indian peninsula or Central Africa. We aimed at assessing the impact of travel on Blastocystis carriage and seek associations between Blastocystis and the bacterial microbiota.Results: We found a prevalence of Blastocystis of 16/35 (46%) before travel and 15/35 (43%) after travel. The two most commonly Blastocystis subtypes (STs) found were ST3 and ST4, accounting for 20 of the 31 samples positive for Blastocystis. No mixed subtype carriage was detected. All ten individuals with a typable ST before and after travel maintained their initial ST. The composition of the gut bacterial community was not significantly different between Blastocystis-carriers and non-carriers. Interestingly, the presence of Blastocystis was accompanied with higher abundances of the bacterial genera Sporolactobacillus and Candidatus Carsonella. Blastocystis carriage was positively associated with high bacterial genus richness, and negatively correlated to the Bacteroides-driven enterotype. These associations were both largely dependent on ST4 – a subtype commonly described from Europe – while the globally prevalent ST3 did not show such significant relationships.Conclusions: The high rate of Blastocystis subtype persistence found during travel indicates that long-term carriage of Blastocystis is common. The associations between Blastocystis and the bacterial microbiota found in this study could imply a link between Blastocystis and a healthy microbiota as well as with diets high in vegetables. Whether the associations between Blastocystis and the microbiota are resulting from the presence of Blastocystis, or are a prerequisite for colonization with Blastocystis, are interesting questions for further studies.
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| 3. |
- Granlund, Margareta, et al.
(författare)
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Discrepancies in Antimicrobial Susceptibility between the JP2 and the Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans
- 2022
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Ingår i: Antibiotics. - Basel : MDPI. - 0066-4774 .- 2079-6382. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125–0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC90 values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed.
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| 4. |
- Pettersson, Mattias, 1972-, et al.
(författare)
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Effect of cobalt ions on the interaction between macrophages and titanium
- 2018
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Ingår i: Journal of Biomedical Materials Research. Part A. - : John Wiley & Sons. - 1549-3296 .- 1552-4965. ; :9, s. 2518-2530
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation and bone reduction around dental implants are described as periimplantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL-1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro-inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP-1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL-1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy (ICP-AES) and electron microscopy. Co at a concentration of 100 μM neutralized the IL-1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti-induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti-induced activation and release of active IL-1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal-protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localization after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri-implant tissue.
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| 5. |
- Pettersson, Mattias, 1972-
(författare)
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On titanium release from dental implants and the inflammatory response
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In dentistry, dental implants have become a standard treatment for single tooth loss and partial and total edentulism since their introduction by P-I Brånemark in the 1960s. Long-term follow-up studies have shown that dental implantation is a predictable treatment, with an overall implant survival over ninety-five percent. Mucositis and peri-implantitis are types of inflammation in the peri-implant soft tissue, and the latter occurs with the simultaneous loss of supporting bone. The pathogenesis of mucositis and peri-implantitis is considered a microbial infection in the peri-implant tissue that causes bone loss induced by inflammation. Immune and resident cells are activated by bacterial products and toxins, which induce the release of a cascade of proinflammatory cytokines and chemokines that can activate osteoclasts and cause further bone resorption. Noninfection-induced inflammatory reactions caused by wear particles from an orthopedic implant leading to loss of the prosthesis is a well-known condition in orthopedics. This immune response induced by metal particles has been shown to act by the assembly of a protein complex, i.e., an inflammasome, in macrophages, leading to the release of proinflammatory cytokines, e.g., interleukin 1 beta (IL-1β). Whether metal particles from a dental implant are associated in the pathogenesis of peri-implantitis has not yet been investigated thoroughly. Although titanium dioxide (TiO2) nanoparticles are known to induce a proinflammatory response, the relation between titanium (Ti) and peri-implantitis is not known.The overall aim of this thesis was to gain knowledge of the proinflammatory capacity of Ti and its potential association with the pathogenesis of peri-implantitis. The null hypothesis in this thesis is that Ti has no proinflammatory effect.To investigate the proinflammatory capacity of Ti, we exposed macrophages derived from a human cell line and monocytes isolated from human blood to Ti. We identified the activation and release of the proinflammatory cytokine IL-1β after the exposure of human macrophages to Ti ions, indicating activation of the inflammasome complex. A five-fold increase in the release of IL-β was found when cells were primed with bacterial products, e.g., Escherichia coli lipopolysaccharide (E. coli LPS) prior to exposure to Ti in culture medium. The proinflammatory effect of Ti was shown to be mediated by metal-protein aggregates formed in the medium and phagocytosed by macrophages. The exposure of macrophages to E. coli LPS mediates the production of intracellular pro-IL-1β, and a second stimulus is needed to cleave the proform of the cytokine, resulting in active IL-1β. Caspase-1, an intracellular protein, is activated through the assembly of the inflammasome complex and is needed for the activation of pro-IL-1β into its active form. Our findings indicate that the Ti-induced activation and release of IL-1β is mediated through the inflammasome complex, as the effect was reduced in the presence of a caspase-1 inhibitor. Peri-implantitis and periodontitis soft tissue samples were investigated chemically and microscopically, and a high content of Ti could be identified in the peri-implantitis tissue samples. The Ti particles identified in the peri-implantitis soft tissue might aggravate the inflammatory response and jeopardize the peri-implant treatment outcome. Transmission electron microscopy (TEM) was used to visualize the formed Ti-protein aggregates, and we discovered that the morphology of the aggregates differed in the presence of cobalt (Co). By microscopy, we could show the uptake of Ti-protein aggregates into macrophage phagolysosomes and that the location of these aggregates differed when Co was present. The origin of the Ti particles found in peri-implantitis soft tissue is unknown, but we could show that Ti is abraded from the implant during insertion into the bone. This abrasion of Ti from the implant surface into the bone is more prominent from an implant with a rough surface than with a smooth surface. We can conclude that Ti can act as a secondary stimulus to macrophages and activate the release of active IL-1β via inflammasome complex assembly. Additionally, Ti forms metal-protein aggregates with a proinflammatory effect that can be inhibited by the presence of Co. Peri-implantitis soft tissue samples contained high concentrations of Ti and metal fragments. Lastly, Ti particles are abraded from the implant during insertion into the bone in amounts that could be proinflammatory. The proinflammatory effect induced by Ti can act in synergy with infection-induced inflammation and cause an imbalance in the host response, leading to the progression of peri-implantitis. The null hypothesis could be rejected.
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| 6. |
- Pettersson, Mattias, et al.
(författare)
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Release of titanium after insertion of dental implants with different surface characteristics : an ex vivo animal study
- 2017
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Ingår i: Acta Biomaterialia Odontologica Scandinavica. - : Taylor & Francis. - 2333-7931. ; 3:1, s. 63-73
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, amount of titanium (Ti) released into the surrounding bone during placement of implants with different surface structure was investigated. Quantification of Ti released during insertion from three different implants was performed in this ex vivo study. Jaw bone from pigs was used as model for installation of the implants and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) was used for analysis of the released Ti. Implant surface were examined with scanning electron microscopy (SEM), before and after the placement into the bone. Ti was abraded to the surrounding bone upon insertion of a dental implant and the surface roughness of the implant increased the amount of Ti found. Diameter and total area of the implant were of less importance for the Ti released to the bone. No visible damages to the implant surfaces could be identified in SEM after placement.
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| 7. |
- Pettersson, Mattias, et al.
(författare)
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Titanium ions form particles that activate and execute interleukin-1β release from lipopolysaccharide-primed macrophages
- 2017
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 52:1, s. 21-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Peri-implantitis is a destructive inflammatory process characterized by destruction of the implant-supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri-implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples.MATERIAL AND METHODS: Human macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell-culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin-1β (IL-1β) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively.RESULTS: Ti ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL-1β release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 μm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 μm) to stimulate secretion of IL-1β from human macrophages in vitro.CONCLUSION: Ti ions form particles that act as secondary stimuli for a proinflammatory reaction.
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| 8. |
- Pettersson, Mattias, 1972-, et al.
(författare)
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Titanium release in peri-implantitis
- 2019
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 46:2, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or periodontitis and to examine whether Ti particles can be identified in samples from peri-implantitis lesions.Background: Long-term follow-up studies show that implant usage to replace missing or lost teeth is a safe and predictable treatment. However, inflammation and loss of supporting bone around an implant (peri-implantitis) lead to patient suffering and costs. Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis tissue is unknown.Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analyzed with inductively coupled plasma mass spectrometry (ICP-MS) for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analyzed microscopically with light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) with element analysis to investigate the presence of particulate Ti.Results: All patients lost one or more implants despite undergoing peri-implant or periodontal treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than periodontitis tissue with a mean ± SDof 98.7 ± 85.6 μg/g and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and periodontitis biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue. The mean size ± SDof the visible particles with LM was 10.9 ± 35.7 μm2 (mean of three repeated measurements) (95% CI, 6.5-15.3).Conclusion: We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions.
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| 9. |
- Ramström, Margareta, et al.
(författare)
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Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry
- 2004
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Ingår i: Proteomics. ; :4, s. 4010-4018
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Tidskriftsartikel (refereegranskat)abstract
- This study demonstrates the power of a novel proteomic approach developed for the detection and identification of biological markers in body fluids. The goal was to observe alterations in the protein patterns of cerebrospinal fluid (CSF) related to amyotrophic lateral sclerosis (ALS), a neuro-degenerative disorder with unknown etiology. In the experiments, tryptic digests of CSF from patients and healthy controls were analyzed by on-line capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Typically, around 4000 peptides were detected in one such experiment, and a pattern recognition program was constructed for the data analysis to distinguish mass chromatograms from patients and controls. This strategy was evaluated comparing the peptide patterns of CSF spiked in vitro with a biomarker, with control CSF. The patterns were clearly separated and the tryptic peptides of the biomarker were successfully selected as characteristic peaks. Hence, the method was applied to compare mass chromatograms of CSF from 12 ALS-patients and 10 matched healthy controls. While no biomarker alone could be identified from the characteristic peaks, we were able to assign 4 out of 5 unknown samples correctly (i.e. 80% correctly diagnosed, 20% false-negative), and it would be 100% if we reject a possible outlier believed to be caused by an occlusion in the spinal CSF compartment. These findings are very promising, although the clinical relevance is not fully established due to the low number of unknown samples analyzed. In addition to the diagnostic potential, these results may be important steps towards understanding the neurodegenerative process.
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| 10. |
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