| 238591. |
- Römhild, Roderich, et al.
(author)
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Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin
- 2020
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In: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 18:1
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Journal article (peer-reviewed)abstract
- Antibiotic resistance increasingly limits the success of antibiotic treatments, and physicians require new ways to achieve efficient treatment despite resistance. Resistance mechanisms against a specific antibiotic class frequently confer increased susceptibility to other antibiotic classes, a phenomenon designated collateral sensitivity (CS). An informed switch of antibiotic may thus enable the efficient treatment of resistant strains. CS occurs in many pathogens, but the mechanisms that generate hypersusceptibility are largely unknown. We identified several molecular mechanisms of CS against the antibiotic nitrofurantoin (NIT). Mutants that are resistant against tigecycline (tetracycline), mecillinam (beta-lactam), and protamine (antimicrobial peptide) all show CS against NIT. Their hypersusceptibility is explained by the overexpression of nitroreductase enzymes combined with increased drug uptake rates, or increased drug toxicity. Increased toxicity occurs through interference of the native drug-response system for NIT, the SOS response, with growth. A mechanistic understanding of CS will help to develop drug switches that combat resistance.
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| 238592. |
- Rønholm, Ebbe, 1960, et al.
(author)
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Complement system activation during orthotopic liver transplantation in man. Indications of peroperative complement system activation in the gut.
- 1994
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In: Transplantation. - 0041-1337. ; 57:11, s. 1594-7
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Journal article (peer-reviewed)abstract
- Sixteen patients with acute and chronic liver disease undergoing OLT were studied regarding the role of the liver and the gut in complement activation. Also, the relation between complement activation and clinical manifestations during the liver transplantation reperfusion period was investigated. Blood samples for measurement of complement anaphylatoxin C3a (C3a), complement anaphylatoxin C5a (C5a), and terminal C5b-9 complement complex (TCC) were taken simultaneously from the central venous catheter and the radial arterial line before starting the operative procedure, 1 min before declamping, and 1-2 min, 5 min, 30 min and 6-12 hr after declamping. Simultaneous blood sampling from the radial arterial line, central venous catheter, portal vein, and hepatic vein was performed 1-2 min and 5 min after completed unclamping. Elevated plasma levels of C3a and TCC were found upon reperfusion, while C5a levels remained unchanged throughout the operation compared with the preoperative levels. The levels of C3a in the portal vein were higher compared with the levels in the simultaneously obtained samples from the radial artery. The results indicate complement cascade activation located to the gut during the reperfusion phase of OLT. Seventy-five percent of the patient studied suffered from the postreperfusion syndrome, indicated by profound hypotension upon reperfusion of the transplanted liver. There was a significant correlation between high concentration of C3a anaphylatoxin and development of profound hypotension.
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| 238593. |
- Rönmark, Erik P, 1981
(author)
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The association between eczema, asthma and rhinitis -population studies of prevalence and risk factors among adults
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: Allergic diseases such as asthma, rhinitis and eczema have increased significantly since the middle of the past century and are now common conditions among both children and adults. The increase was observed earlier and is more evident in Westernized countries but is now also apparent in urbanized areas in developing countries. The exact cause of this increase is still not fully explored, although several partly contradicting hypotheses exist, including the hygiene hypothesis. Asthma, rhinitis and eczema are common comorbidities and allergic sensitization is commonly seen as a unifying link. Research questions: The overall aim of this thesis was to investigate the prevalence of eczema; risk factors for eczema; overlapping risk factors for asthma, rhinitis and eczema; the prevalence of allergic sensitization and the impact of allergic sensitization on these diseases in an adult population. Additional objectives included a validation of the representativeness of the recruited population. Methodology: This thesis is based on a postal survey in Västra Götaland with 18 087 responders (62%) out of a real study sample of 29 218 individuals aged 16 to 75 years. Clinical examinations including structured interviews, lung function tests, anthropometric measures, skin prick tests and assessments of specific serum Immunoglobulin E were performed in 1172 randomly selected responders. A study of non-response was carried out among non-responders to the postal survey and 211 out of the 400 randomly selected subjects were successfully contacted by phone and agreed to participate. Results: Non-responders compared to responders to the postal survey tended to be younger, smoke, have male sex and live in the metropolitan area of Gothenburg but they did not differ in prevalence of asthma, airway symptoms, eczema and rhinitis. Ever having had eczema was reported by 40.7% in the postal survey and the prevalence of current eczema was 11.5%. Eczema was more common among women and associated with respiratory symptoms, asthma and rhinitis. Allergic sensitization, obesity, female sex and occupational exposure to gas, dust or fumes were significantly and independently associated with asthma. A risk factors for rhinitis but not for eczema was obesity and allergic sensitization was strongly associated with rhinitis but less so for eczema. Risk factors for eczema but not for rhinitis were female sex and occupational exposure to gas, dust or fumes. Farm childhood was negatively associated with rhinitis and eczema but not asthma. The prevalence of sensitization to at least one common airborne allergen was 29.7%. Sensitization to birch and dog was associated with asthma while rhinitis was associated with sensitization to birch and timothy. No significant association was found between allergic sensitization and current eczema. Conclusions: We conclude that non-response had minimal effect on the outcome in our study. Eczema was more common than anticipated and associated with asthma and rhinitis. There are different risk factor patterns for asthma, rhinitis and eczema in adults. Allergic sensitization is an important risk factor for asthma and rhinitis but less so for eczema among adults. Rhinitis is mainly associated with sensitization to outdoor allergens while asthma is related to both outdoor and indoor allergens.
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| 238594. |
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| 238595. |
- Rönn, Tina, et al.
(author)
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Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a six months exercise intervention.
- 2014
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In: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 211:1, s. 188-200
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Journal article (peer-reviewed)abstract
- Adipose tissue has an important function in total energy homeostasis and its dysregulation may contribute to life-style related diseases such as type 2 diabetes, cancer and cardiovascular diseases. The aim of this study was to investigate genome-wide mRNA expression in adipose tissue in healthy men before and after an exercise intervention to identify genes or pathways that mediate the beneficial effect of regular exercise. We also investigated the difference in adipose tissue mRNA expression between individuals with or without a family history of type 2 diabetes.
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| 238596. |
- Rönnback, Annica, et al.
(author)
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Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions
- 2012
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:4
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Journal article (peer-reviewed)abstract
- The Arctic APP mutation (E693G) within the amyloid beta (A beta) domain of amyloid precursor protein (APP) leads to dementia with clinical features similar to Alzheimer's disease (AD), which is believed to be mediated via increased formation of protofibrils. We have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human amyloid precursor protein with the Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late onset. Here we performed a detailed analysis of the spatiotemporal progression of neuropathology in homozygous TgAPParc, focusing on intracellular A beta and diffuse A beta aggregates rather than amyloid plaques. We show that the neuropathology in homozygous TgAPParc mice starts with intracellular A beta aggregates, which is followed by diffuse extracellular A beta deposits in subiculum that later expands to brain regions receiving neuronal projections from regions already affected. Together this suggests that the pathology in TgAPParc mice affects interconnected brain regions and may represent a valuable tool to study the spread and progression of neuropathology in Alzheimer's disease.
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| 238597. |
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| 238598. |
- Rönnberg, Henrik, et al.
(author)
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A dose-finding study with a novel water-soluble formulation of paclitaxel for the treatment of malignant high-grade solid tumours in dogs
- 2013
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In: Veterinary and Comparative Oncology. - : Wiley. - 1476-5810 .- 1476-5829. ; 11, s. 243-255
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Journal article (peer-reviewed)abstract
- A new formulation of water-soluble paclitaxel (Paccal (R) Vet) has been developed for canine cancer patients, without the need for pre-medication (traditionally required in non-water-soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression-free and overall survival and to evaluate single-dose pharmacokinetics in tumour-bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150mg m(-2) intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression-free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water-soluble formulation of paclitaxel suggesting successful administration and being safely used without pre-medication in dogs.
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| 238599. |
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| 238600. |
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