| 1. |
- Demirel, Isak, et al.
(författare)
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Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli
- 2013
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 121:2, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Suppressor of cytokine signalling (SOCS) proteins inhibit pro-inflammatory signalling mediated by Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathways. To evade the immune response some pathogens appear to modify the host SOCS proteins. Uropathogenic Escherichia coli (UPEC) are able to subvert the host response evoked by bladder epithelial cells, but the mechanisms are not fully understood. The objective of this study was to investigate whether UPEC can modify the host SOCS and STAT3 response. Real time RT-PCR studies demonstrated an increased SOCS1 and SOCS3 expression in the isolated human bladder epithelial cell lines (RT-4 and 5637) in response to cytokines. UPEC strain IA2 increased SOCS3, but not SOCS1, mRNA levels with a peak at 6h after infection. The increase of SOCS3 was confirmed at the protein level by Western blotting. The UPEC strain IA2 caused a time-dependent decrease in the phosphorylation of STAT3. This study demonstrates that UPEC are able to affect SOCS3 and STAT3 signalling in human uroepithelial cells. The finding that UPEC are able to induce mediators involved in suppression of host cytokine signalling may help to elucidate how UPEC may circumvent the host response during urinary tract infection.
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| 2. |
- Nygårdh, Annette, et al.
(författare)
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Empowerment Intervention in Outpatient Care of Persons with Chronic Kidney Disease Pre-Dialysis
- 2012
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Ingår i: Nephrology Nursing Journal. - 1526-744X .- 2163-5390. ; 39:4, s. 285-293
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Tidskriftsartikel (refereegranskat)abstract
- Empowering interventions can improve person-centered care. A pre- and post-evaluation using interactive research involving two years of empowering interventions was designed to improve quality of care in outpatients with chronic kidney disease who were pre-dialysis. The results showed significantly increased empowerment in the intervention group. Interactive research facilitated the implementation of the empowerment intervention, which may increase sustainability over time.
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| 3. |
- Demirel, Isak, 1987-, et al.
(författare)
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Nitric oxide activates IL-6 production and expression in human renal epithelial cells
- 2012
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Ingår i: American Journal of Nephrology. - Basel, Switzerland : S. Karger. - 0250-8095 .- 1421-9670. ; 36:6, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Increased nitric oxide (NO) production or inducible form of NO synthase activity have been documented in patients suffering from urinary tract infection (UTI), but the role of NO in this infection is unclear. We investigated whether NO can affect the host response in human renal epithelial cells by modulating IL-6 production and mRNA expression. Methods: The human renal epithelial cell line A498 was infected with a uropathogenic Escherichia coli (UPEC) strain and/or the NO donor DETA/NO. The IL-6 production and mRNA expression were evaluated by ELISA and real-time RT-PCR. IL-6 mRNA stability was evaluated by analyzing mRNA degradation by real-time RT-PCR.Results: DETA/NO caused a significant (p < 0.05) increase in IL-6 production. Inhibitors of p38 MAPK and ERK1/2 signaling, but not JNK, were shown to significantly suppress DETA/NO-induced IL-6 production. UPEC-induced IL-6 production was further increased (by 73 ± 23%, p < 0.05) in the presence of DETA/NO. The IL-6 mRNA expression increased 2.1 ± 0.17-fold in response to DETA/NO, while the UPEC-evoked increase was pronounced (20 ± 4.5-fold). A synergistic effect of DETA/NO on UPEC-induced IL-6 expression was found (33 ± 7.2-fold increase). The IL-6 mRNA stability studies showed that DETA/NO partially attenuated UPEC-induced degradation of IL-6 mRNA.Conclusions: NO was found to stimulate IL-6 in renal epithelial cells through p38 MAPK and ERK1/2 signaling pathways and also to increase IL-6 mRNA stability in UPEC-infected cells. This study proposes a new role for NO in the host response during UTI by modulating the transcription and production of the cytokine IL-6.
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| 4. |
- Axelsson, Lena, et al.
(författare)
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Processes toward the end of life and dialysis withdrawal Physicians' and nurses' perspectives
- 2020
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Ingår i: Nursing Ethics. - : Sage Publications. - 0969-7330 .- 1477-0989. ; 27:2, s. 419-432
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nurses and physicians in nephrology settings provide care for patients with end-stage kidney disease receiving hemodialysis treatment along a complex illness trajectory. Aim: The aim was to explore physicians' and nurses' perspectives on the trajectories toward the end of life involving decisions regarding hemodialysis withdrawal for patients with end-stage kidney disease. Research design and participants: A qualitative research approach was used. Four mixed focus group interviews were conducted with renal physicians (5) and nurses (17) in Sweden. Qualitative content analysis was used to analyse data. Ethical considerations: Ethical approval was obtained (Dnr 2014/304-31). Findings and discussion: Findings illuminated multi-faceted, intertwined processes encompassing healthcare professionals, patients, and family members. The analysis resulted in four themes: Complexities of initiating end-of-life conversations, Genuine attentiveness to the patient's decision-making process, The challenge awaiting the family members' processes, and Negotiating different professional responsibilities. Findings showed complexities and challenges when striving to provide good, ethical care which are related to beneficence, nonmaleficence, and self-determination, and which can give rise to moral distress. Conclusion: There are ethical challenges and strains in the dialysis context that healthcare professionals may not always be prepared for. Supporting healthcare professionals in not allowing complexities to hinder the patient's possibilities for shared decision-making seems important. An open and continual communication, including family meetings, from dialysis initiation could serve to make conversations involving decisions about hemodialysis withdrawal a more natural routine, as well as build up a relationship of trust necessary for the advance care planning about the end of life. Healthcare professionals should also receive support in ethical reasoning to meet these challenges and handle potential moral distress in the dialysis context.
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| 5. |
- Halbgebauer, Rebecca, et al.
(författare)
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Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk for adverse outcome. Recently, thirty-eight-negative kinase 1 (TNK1) was proposed to play a detrimental role in organ damage after trauma/HS. Therefore, we aimed to assess the role of TNK1 in HS-induced kidney injury in a murine and apost hocanalysis of a non-human primate model of HS comparable to the clinical situation. Mice and non-human primates underwent resuscitated HS at 30 mmHg for 60 min. 5 h after the induction of shock, animals were assessed for systemic inflammation and TNK1 expression in the kidney.In vitro, murine distal convoluted tubule cells were stimulated with inflammatory mediators to gain mechanistic insights into the role of TNK1 in kidney dysfunction. In a translational approach, we investigated blood drawn from either healthy volunteers or severely injured patients at different time points after trauma (from arrival at the emergency room and at fixed time intervals until 10 days post injury; identifier: NCT02682550,). A pronounced inflammatory response, as seen by increased IL-6 plasma levels as well as early signs of AKI, were observed in mice, non-human primates, and humans after trauma/HS. TNK1 was found in the plasma early after trauma-HS in trauma patients. Renal TNK1 expression was significantly increased in mice and non-human primates after HS, and these effects with concomitant induction of apoptosis were blocked by therapeutic inhibition of complement C3 activation in non-human primates. Mechanistically,in vitrodata suggested that IL-6 rather than C3 cleavage products induced upregulation of TNK1 and impaired barrier function in renal epithelial cells. In conclusion, these data indicate that C3 inhibitionin vivomay inhibit an excessive inflammatory response and mediator release, thereby indirectly neutralizing TNK1 as a potent driver of organ damage. In future studies, we will address the therapeutic potential of direct TNK1 inhibition in the context of severe tissue trauma with different degrees of additional HS.
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| 6. |
- Hurtig, Caroline, et al.
(författare)
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Patient participation in end-stage kidney disease care : variation over time and effects of staff-directed interventions - a quasi-experimental study
- 2023
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Ingår i: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Among those elements establishing decent quality of care from a patient perspective, opportunities to participate in accord with one's individual needs and preferences are central. To date, little is known the extent of preference-based patient participation in kidney care, and what facilitates optimal conditions. This study investigated i) preference-based patient participation in kidney care over time, and ii) the effects of interventions designed to enhance person-centred patient participation.Methods A quasi-experimental study was conducted across nine kidney care sites in southeast Sweden. A cohort of 358 patients with stage IV chronic kidney disease (eGRF 15-19 ml/min) or V (eGRF < 15 mL/min) entered the study. Of these, 245 patients (with kidney replacement therapy or intermittent outpatient visits only) completed a survey on patient participation at four time points: every six months from August 2019 to May 2021, patients reported their preferences for and experiences of participation using the validated Patient Preferences for Patient Participation tool, the 4Ps. Between the first and second data collection points, interventions were provided for designated staff to facilitate person-centred participation, using two strategies for two subgroups at three sites each: the managers receiving a bundle of information via e-mail on patient participation in a standard dissemination procedure (three sites), or an additional half-year support program for implementation offered to 1-2 staff per site (three sites), with no intervention for a control group (three sites). The differences in 4Ps data between groups were analysed using multilevel ordinal regression.Results Over time and across all sites, most patients' experiences of participation fully or almost fully matched their engagement preferences (57%-90%). Still, up to 12% of patient reports indicated that their preferences and experiences were insufficiently matched: in these cases, the patients had preferred to be more involved than they had experienced, for example, in making healthcare plans and setting health-related goals. The interventions did not affect the levels of preference-based participation, but patients in the control group sites had slightly more consistent matches.Conclusions Living with kidney failure necessitates patient engagement, but opportunities to participate in accordance with one's preferences are not fully provided for all patients. Additional efforts to support a common understanding and to ensure person-centred patient participation is still needed.
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| 7. |
- Svensson, Lovisa, et al.
(författare)
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The effect of nitric oxide on adherence of P-fimbriated uropathogenic Escherichia coli to human renal epithelial cells
- 2010
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Ingår i: BJU International. - Malden, USA : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 105:12, s. 1726-1731
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine the effect of nitric oxide (NO), an endogenous component of the host defence in urinary tract infection, on the adherence of P-fimbriated uropathogenic Escherichia coli (UPEC) to human renal epithelial cells.Materials and Methods: Two wild-type UPEC strains (AD110 and IA2) and the P-fimbriated recombinant strain HB101pPIL-75 were used. Bacteria were allowed to adhere to the human renal epithelial cell line A498 and attachment was evaluated in the absence or presence of the NO donor DETA/NONOate (1 mm). Total RNA was extracted from NO-exposed bacteria in static urine cultures, followed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of the papG gene that encodes the P-fimbriae adhesin PapG.Results: Bacterial adherence to A498 cells was fimbriae-dependent and the ability to agglutinate human P-1 positive erythrocytes confirmed that the used strains were P-fimbriated. UPEC strains AD110 and IA2 attached by a mean of 8 bacteria/cell and 20 bacteria/cell, respectively. In the presence of DETA/NONOate, the attachment of AD110 and IA2 to A498 cells was significantly reduced by a mean (sem) of 34 (3.9)% and 45 (14)%, respectively. The expression of papG was decreased after DETA/NONOate exposure as shown by semiquantitative RT-PCR.Conclusion: NO disrupted functional adhesion of P-fimbriated UPEC to kidney epithelial cells, suggesting that NO-production from epithelial cells in the urinary tract may limit bacterial colonization at the mucosal surface. The reduced adherence may involve transcriptional effects of NO on papG expression, but further studies are needed to establish the underlying mechanisms.
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| 8. |
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| 9. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Hemodialys, inflammation och det naturliga immunsystemet
- 2018
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Ingår i: Vaskulär Medicin. - : Svensk förening för hypertoni, stroke och vaskulär medicin. - 2000-3188 .- 2001-8150. ; 34:3, s. 17-21
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Hemodialys är en livräddande behandling vid kronisk njursvikt, men dialyspatienter har också en kraftigt ökad risk för kardiovaskulär sjukdom. Dialys utgör en enorm utmaning för kroppens naturliga immunsystem (”innate immunity”) eftersom patientens blod under behandlingen kommer i direkt kontakt med kroppsfrämmande ytor såsom i membran, slangar, och pumpar mm. Då sker aktivering av blodets olika protein-system: främst komplementsystemet, kontakt/kallikreinsystemet och koagulationsystemet, vilket initialt leder till en lokal inflammation i anslutning till materialytan i dialyskretsen, men också generering av inflammatoriska mediatorer, till exempel anafylatoxiner och bradykinin. Dessa substanser transporteras sedan med blodet till patienten tillsammans med aktiverade leukocyter och trombocyter som aktiverar endotelet i patientens kardiovaskulära system, som då kan förlora sina normala anti-inflammatoriska och anti-trombotiska funktioner. Sammantaget resulterar detta i en kronisk inflammation som kan leda till atherogenes och arterioskleros. Möjliga strategier att dämpa dessa reaktioner inkluderar val av antikoagulantia med högre specificitet än de typer av heparin som används idag, samt ytmodifiering av de material som ingår i dialyskretsen.
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| 10. |
- Huang, Shan, et al.
(författare)
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Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood
- 2015
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 8:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.
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