| 1. |
- Henriksnäs, Johanna, 1973-
(författare)
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Helicobacter pylori and Gastric Protection Mechanisms : An in vivo Study in Mice and Rats
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The stomach is frequently exposed to hazardous agents and to resist this harsh environment, several protective mechanisms exist. Of special interest is the gastric pathogen Helicobacter pylori which causes gastritis, ulcers and cancer but the mechanism leading to these diseases are still unclear. However it is very likely that H. pylori negatively influence the protection mechanisms that exist in the stomach. The aims of the present investigation were first to develop an in vivo mouse model in which different protection mechanisms could be studied, and second to investigate the influence of H. pylori on these mechanisms. An in vivo preparation of the gastric mucosa in mice was developed. This preparation allows studies of different gastric mucosal variables and can also be applied for studies in other gastro-intestinal organs. Mice chronically infected with H. pylori, were shown to have a reduced ability of the mucosa to maintain a neutral pH at the epithelial cell surface. This could be due to the thinner inner, firmly adherent mucus gel layer, and/or to defective bicarbonate transport across the epithelium. The Cl-/HCO3- exchanger SLC26A9 was inhibited by NH4+, which also is produced by H. pylori. The mRNA levels of SLC26A9 were upregulated in infected mice, suggesting a way to overcome the inhibition of the transporter. Furthermore, the hyperemic response to acid pH 2 and 1.5 was abolished in these mice. The mechanisms by which the bacteria could alter the blood flow response might involve inhibition of the epithelial iNOS.Water extracts of H. pylori (HPE) reduces the blood flow acutely through an iNOS and nerve-mediated pathway, possibly through the endogenous iNOS inhibitor ADMA. Furthermore, HPE alters the blood flow response to acid as the hyperemic response to acid pH 0.8 is accentuated in mice treated with HPE.
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| 2. |
- Carstens, Adam, 1975-
(författare)
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Chronic inflammatory bowel diseases : studies of microbiota and its influence
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Inflammatory bowel diseases are becoming increasingly common. The underlying mechanisms are not entirely known but the gut microbiota seem to be involved in the pathogenesis. Aim: The aim of this thesis was to characterise gut microbiota related to diagnosis, disease course and response to biological treatment, taking aspects of the source of biological material into account. Materials and methods: Patients and healthy individuals from several different cohorts in Sweden and Europe were invited. Faecal samples and mucosal biopsies were analysed using different sequencing platforms to investigate the gut microbiota. In Study I the faecal microbiota was correlated to different inflammatory bowel diseases. In Study II we compared the microbiota in faeces to the microbiota in mucosal biopsies. In StudyIII we related the faecal microbiota to the outcome of biological treatment. In Study IV we investigated the diagnostic and prognostic properties of the GAmapTM Dysbiosis Test.Results: The faecal microbiota in collagenous colitis resembles the faecalmicrobiota in inflammatory bowel disease. The faecal microbiota differs from the mucosal microbiota. Faecal microbiota at initiation of biological treatment among patients with Crohn’s disease differ between responders and non-responders. The GAmapTM Dysbiosis Test discriminates patients with inflammatory bowel disease from healthy individuals.Conclusion: Collagenous colitis may share microbial underpinnings with other inflammatory bowel diseases. Conclusions about mucosal interactions with the gut microbiota should be made with caution when usingfaecal samples to characterise the microbiota. In Crohn’s disease, the faecal microbiota may be included in a model to predict the outcome of biological treatment. The GAmap Dysbiosis Test does not seem to be superior to other current diagnostic tools in clinical decision-making.
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| 3. |
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| 4. |
- Gorski, Dmitri
(författare)
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ATMP Process : Improved Energy Efficiency in TMP Refining Utilizing Selective Wood Disintegration and Targeted Application of Chemicals
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on the novel wood chip refining process called AdvancedThermomechanical Pulp (ATMP) refining. ATMP consists of mechanical pretreatmentof chips in Impressafiner and Fiberizer prior to first stage refining atincreased intensity. Process chemicals (this study was concentrated on hydrogenperoxide and magnesium hydroxide) are introduced into the first stage refiner.It is known that the use of chemicals in TMP process and first stage refining atelevated intensity can reduce the energy demands of refining. The downside is thatthey also alter the character of the produced pulp. Reductions in fibre length andtear index are usually the consequences of refining at elevated intensity. Additionof chemicals usually leads to reduction of the light scattering coefficient. Usingstatistical methods it was shown that it is possible to maintain the TMP character ofthe pulp using the ATMP process. This is explained by a separation of thedefibration and the fibre development phases in refining. This separation allowsdefibration of chips to fibres and fibre bundles without addition of chemicals orincrease in refining intensity. Chemicals are applied in the fibre developmentphase only (first stage refiner). The energy demand in refining to reach tensileindex of 25 Nm/g was reduced by up to 1.1 MWh/odt (42 %) using the ATMPprocess on Loblolly pine. The energy demand in refining of White spruce, requiredto reach tensile index of 30 Nm/g, was reduced by 0.65 MWh/odt (37%).Characterizations of individual fibre properties, properties of sheets made fromlong fibre fractions and model fibre sheets with different fines fractions werecarried out. It was established that both the process equipment configuration (i.e.the mechanical pre‐treatment and the elevated refining intensity) and the additionof process chemicals in the ATMP process influence fibre properties such as external and internal fibrillation as well as the amount of split fibres. Improvementof these properties translated into improved properties of sheets, made from thelong fibre fractions of the studied pulps. The quality of the fines fraction alsoimproved. However, the mechanisms of improvement in the fines quality seem tobe different for fines, generated using improved process configuration andaddition of process chemicals. The first type of fines contributed to better bondingof model long fibre sheets through the densification of the structure. Fines whichhave been influenced by the addition of the process chemicals seemed in additionto improve bonding between long fibres by enhancing the specific bond strength.The improved fibre and fines properties also translated into better airpermeability and surface roughness of paper sheets, properties which areespecially important for supercalendered (SC) printing paper. The magnitude offibre roughening after moistening was mainly influenced by the processequipment configuration while the addition of process chemicals yielded lowestfinal surface roughness due to the lowest initial surface roughness. There was nodifference in how fines fractions from the studied processes influenced the fibreroughening. However, fines with better bonding yielded model fibre sheets withhigher PPS, probably due to their consolidation around fibre joints. Hence, thedecrease in PPS can probably be attributed to the improvements in the long fibrefraction properties while the improvement of fines quality contributed to thereduction of air permeability.The process chemicals, utilized in the ATMP process (Mg(OH)2 and H2O2) alsoproved to be an effective bleaching system. Comparable increases in brightnesscould be reached using the ATMP process and conventional tower bleaching.Maximum brightness of the pulp was reached after approximately 10 minutes ofhigh‐consistency storage after refining or 40 minutes of conventional bleaching.This study was conducted using a pilot scale refiner system operated as a batchprocess. Most of the experiments were performed using White spruce (Piceaglauca). In Paper I, Loblolly pine (Pinus taeda) was used. It is believed that theresults presented in this thesis are valid for other softwood raw materials as well,but this limitation should be considered.
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| 5. |
- Kampmann, Christian, 1975-
(författare)
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Go with your gut : The human intestinal microbiota, international travel, Campylobacter and ESBL-producing Enterobacteriaceae
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Up to 100 million people travel annually from industrialized countries to resource-limited ones. Each traveller contains an internal ecosystem composed of tens of trillions of microbes, known as the intestinal microbiota, which has a large effect on health. The microbiota seems to be highly individual and mostly stable but can be significantly affected by several factors. Many international travellers are at high risk of getting infected by Campylobacter, the most common cause of bacterial enteritis worldwide. Campylobacter infection can cause a wide range of symptoms, with varying severity, for reasons largely unknown. Travel also radically increases the risk of colonization by antibiotic-resistant intestinal bacteria, notably Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (EPE). To date, there are no therapies available for EPE-decolonization. In this thesis, it was investigated whether the bacterial intestinal microbiota affected susceptibility to Campylobacter and if international travel as such had an impact on the microbiota. In a prospective, observational study, 67 healthy Swedes, travelling in groups to countries with a high risk of Campylobacter infection, were followed. The travellers answered questionnaires and delivered two faecal samples before and three samples after the trip. These samples were cultured for enteropathogens and analysed for the microbiota composition. Low diversity of microbiota seemed to increase the risk of Campylobacter jejuni infection, whereas a high relative abundance of Lachnospiraceae might decrease the risk (Paper I). Furthermore, the overall bacterial diversity did not seem to change in connection with travelling. However, the bacterial family Enterobacteriaceae (otherwise connected with inflammation, infection and antibiotic-resistance) was shown to be dramatically increased in abundance immediately after travel, and the family Christensenellaceae (otherwise connected with beneficial health conditions) simultaneously decreased (Paper II). Eight travellers, from two different destinations, were infected with closely related C. jejuni isolates (ST353CC). The bacterial analysis of genomic and phenotypic characteristics revealed that the C. jejuni isolates of the travellers returning from one of the destinations and with more severe symptoms actually showed less pathogenic potential, compared to the isolates of travellers from the other destination and with milder symptoms. However, the travellers with more severe symptoms had much higher relative abundances of Bacteroidetes in their intestinal microbiota and, in contrast to the other travellers, excluded meat from their diet. (Paper III) Finally, we investigated in a randomized, placebo-controlled clinical trial of 80 established intestinal carriers of EPE, whether the oral probiotic product Vivomixx® could eradicate EPE. Vivomixx® was not superior to placebo (Paper IV).
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| 6. |
- Sjölund, Maria, 1975-
(författare)
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Development and Stability of Antibiotic Resistance
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is of current concern. Bacteria have become increasingly resistant to commonly used antibiotics and we are facing a growing resistance problem. The present thesis was aimed at studying the impact of antibiotic treatment on pathogenic bacteria as well as on the normal human microbiota, with focus on resistance development.Among the factors that affect the appearance of acquired antibiotic resistance, the mutation frequency and biological cost of resistance are of special importance. Our work shows that the mutation frequency in clinical isolates of Helicobacter pylori was generally higher than for other studied bacteria such as Enterobacteriaceae; ¼ of the isolates displayed a mutation frequency higher than Enterobacteriaceae defective mismatch repair mutants and could be regarded as mutator strains.In H. pylori, clarithromycin resistance confers a biological cost, as measured by decreased competitive ability of the resistant mutants in mice. In clinical isolates, this cost could be reduced, consistent with compensatory evolution stabilizing the presence of the resistant phenotype in the population. Thus, compensation is a clinically relevant phenomenon that can occur in vivo.Furthermore, our results show that clinical use of antibiotics selects for stable resistance in the human microbiota. This is important for several reasons. First, many commensals occasionally can cause severe disease, even though they are part of the normal microbiota. Therefore, stably resistant populations increase the risk of unsuccessful treatment of such infections. Second, resistance in the normal microbiota might contribute to increased resistance development among pathogens by interspecies transfer of resistant determinants.
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| 7. |
- Storm, Martin, 1975-
(författare)
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Identification and Characterization of Biomarkers in Bacterial Infections
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years molecular biology has become an integral part of the clinical laboratory. With an ever increasing number of methodologies and applications being presented each year it has increased our knowledge of how bacteria cause disease as well as our ability to predict disease outcome. The main focus of this thesis has been to develop methods for identifying biomarkers and prediction methods for bacterial infectious diseases by taking advantage of the ever increasing possibilities of molecular biology. We applied cutting edge techniques in order to establish novel platforms for identifying and characterizing biomarkers of disease. In paper one we describe a novel approach to measure levels of antibiotic resistance and viability of C. trachomatis, a method that is a clear improvement over existing techniques. In the second paper we describe the development of two assays designed to type pertussis toxin subunit 1 in circulating strains, in order to facilitate multi center studies for vaccine escape surveillance. In paper three we develop a novel microarray application designed to identify a large number of bacterial traits of H. pylori simultaneously with human genetic polymorphisms in order to identify a collection of risk factors that could be used as a prediction tool for gastric cancer risk. In the last paper we define the “antigenome” of H. pylori and identified 14 promising, previously unreported antigens as well as a number of potential biomarkers.The platform technologies described in this collection of papers will hopefully help us identifying novel ways of fighting and predicting bacterial disease in future studies.
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