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- Diab, Kerstin, et al.
(författare)
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Work-related airway symptoms, nasal reactivity and health-related quality of life in female hairdressers: a follow-up study during exposure.
- 2014
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 87:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Hairdressers often complain of work-related rhinitis (WR). They are infrequently sensitized to persulphates. The cause and mechanism of the symptoms and the effects on their health-related quality of life (HRQoL) remains unclear. The objectives were to follow female hairdressers with WR mainly from bleaching powder regarding nasal reactivity to persulphate and to evaluate symptoms, HRQoL and inflammatory markers in nasal lavage during a working period after vacation and compared with hairdressers without symptoms and pollen allergic women. METHODS: Skin prick tests to persulphate were performed in the hairdressers. Participants kept a diary of symptoms and of work tasks (hairdressers only). They completed HRQoL questionnaires. Eosinophil cationic protein (ECP) in nasal lavage fluid was examined. The symptomatic hairdressers performed nasal challenges with persulphate before and after the exposure. RESULTS: Skin prick tests were negative. Although the nasal reactivity to persulphate did not change a steady increase in nasal symptoms, especially blockage, and in ECP was noticed in the symptomatic hairdressers. The HRQoL deteriorated in the symptomatic hairdressers indicating an effect on their working situation and daily life. The atopics had more, but varying symptoms (itching, sneezing and secretion). CONCLUSIONS: The difference in the clinical picture between the symptomatic hairdressers and the pollen allergic women, the increase in symptoms and ECP in the nasal lavage support the view that a sensitization to hairdresser chemicals by a mechanism not yet understood is operating. The deterioration of the HRQoL in the symptomatic hairdressers indicates a considerable effect on their life.
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- Diab, Randa A Hadi Gadalla
(författare)
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Experimental islet transplantation
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pancreatic islet transplantation is a promising treatment modality for patients with insulin- dependent diabetes. Besides whole pancreas transplantation, it is the only treatment that can make patients normoglycemic without risking episodes of hypoglycemia. It can also prevent, slow down and even reverse the development of secondary complications to diabetes. Compared to whole pancreas transplantation, islet transplantation is much less invasive and may also be used in patients with a high surgical risk profile, but clinical outcome data are so far better for whole pancreas transplantation. However, graft survival necessitates life-long immunosuppression and for islet transplantation more than one donor is usually needed. There is therefore a need for more specific immunosuppression with less side effects as well as methods by which the donor pool can be expanded. In this project we have assessed the capability of costimulation blockade, i.e. blocking the second signal of T lymphocyte activation, to prevent rejection of allogeneic (between individuals) and xenogeneic (between species) islet grafts, in particular when transplanted to recipients already sensitized to the graft. We have shown that a triple costimulation blockade regimen with anti-CD154 antibodies, CTLA4Ig and anti-LFA-1 antibodies could not prolong survival of islet allografts when transplanted under the kidney capsule of sensitized C57BL/6 mice. Either induced antibodies or memory T cells may be responsible for this inability of conventional costimulation blockade to prolong graft survival in sensitized animals. We tried to resolve this question in a rat-to-mouse xenotransplantation model, in which immune or naïve serum was injected intraperitoneal at the time of islet transplantation. Again, the recipient animals were given costimulation blockade. The immune serum had no negative impact on the grafts immediately (within 96 hours) post- transplantation or on the graft survival long-term in mice receiving costimulation blockade. These results suggest that preformed antibodies are not the main cause for graft rejection in sensitized recipients treated by costimulation blockade. In the animal transplantation models used, streptozotocin or alloxan is used to induce diabetes through their toxic effects on pancreatic β-cells. It has been reported that these drugs are also toxic for other cells and tissues, including cells of the immune system. Therefore, we compared recipients given streptozotocin or alloxan for diabetes induction with regard to graft survival times, spleen size and toxic effects on leukemic cells in vitro. We conclude that streptozotocin is more toxic on immune cells than alloxan, and may therefore not be a suitable agent for diabetes induction in transplantation models assessing different immunosuppressive protocols. Further, we showed that the erythropoietin analogue, pyroglutamate helix B surface peptide (ARA 290) could protect islets from apoptosis when exposed to pro-inflammatory cytokines in vitro, while no clear effect was seen on graft survival when injected into the recipients. Further studies are needed on this potential islet-protective agent. In conclusion, islet transplantation holds great promise for the future as a treatment modality for insulin-dependent diabetes. However, further research is needed in order to find optimal immunosuppressive protocols with acceptable side effects that can promote long term graft survival. Costimulation blockade may be such a modality provided memory T cell activation can be perturbed and tolerance induced also in sensitized recipients.
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| 4. |
- Diab, Randa A H, et al.
(författare)
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Rat islets are not rejected by anti-islet antibodies in mice treated with costimulation blockade.
- 2014
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Ingår i: Xenotransplantation. - : Wiley. - 1399-3089 .- 0908-665X. ; 21:4, s. 353-66
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Tidskriftsartikel (refereegranskat)abstract
- Costimulation blockade can prevent rejection of islet xenografts in naïve but not sensitized recipients. Donor-specific antibodies (DSA) may partly explain this observation. The effect of DSA on rat islet xenograft survival in mice receiving costimulation blockade was investigated.
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| 5. |
- Diab, R, et al.
(författare)
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Effect of triple costimulation blockade on islet allograft survival in sensitized mice.
- 2010
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 1873-2623 .- 0041-1345. ; 42:6, s. 2109-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8. RESULTS: Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10). CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.
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- Kåredal, Monica, et al.
(författare)
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Time-Dependent Proteomic iTRAQ Analysis of Nasal Lavage of Hairdressers Challenged by Persulfate.
- 2010
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; okt, s. 5620-5628
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Tidskriftsartikel (refereegranskat)abstract
- Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the nasal lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without nasal symptoms, and atopic subjects with pollen-associated nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of nasal lavage fluids. Samples were prepared by pooling nasal lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group.
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