| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Backstrom, E, et al.
(author)
-
Direct NK cell-mediated lysis of syngenic dorsal root ganglia neurons in vitro
- 2000
-
In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 165:9, s. 4895-4900
-
Journal article (peer-reviewed)abstract
- In contrast to extensive studies on the role of T and B lymphocytes in the pathogenesis of autoimmune diseases of the nervous system, little is known about NK cells and their potential role in the destruction of neural tissue. NK cells have been implicated in the selective death of sympathetic neurons resident in the superior cervical ganglia of rats after exposure to the drug guanethidine. This observation suggests that NK cells may function as principle effectors in immunological diseases of the nervous system. However, the direct mechanism of action of NK cells in this model is not known. In particular, it is not known whether NK cells can kill autologous neurons directly. The aim of the present study was to examine whether NK cells can kill directly dorsal root ganglia neurons cultured in vitro. We demonstrate that C57BL/6 (B6)-derived dorsal root ganglia neurons can be killed directly by syngenic IL-2-activated NK cells, and that this nerve cell lysis is dependent on the expression of perforin in the NK cells. NK cells were less effective in destroying neurons grown in the presence of glial cells. These observations indicate a potential role for NK cells in nerve cell degeneration in inflammatory diseases of the nervous system.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Backstrom, E., et al.
(author)
-
Possible Extraction of Drugs from Lung Tissue During Broncho-alveolar Lavage Suggest Uncertainty in the Procedure's Utility for Quantitative Assessment of Airway Drug Exposure
- 2022
-
In: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 111:3, s. 852-858
-
Journal article (peer-reviewed)abstract
- Following inhaled dosing, broncho-alveolar lavage (BAL) is often used for sampling epithelial lining fluid (ELF) to determine drug concentration in the lungs. This study aimed to explore the technique's suitability. Urea is typically used to estimate the dilution factor between the BAL fluid and physiological ELF, since it readily permeates through all fluids in the body. As representatives of permeable small molecule drugs with high, medium and low tissue distribution properties, propranolol, diazepam, indomethacin and AZD4721 were infused intravenously to steady state to ensure equal unbound drug concentrations throughout the body. The results showed that propranolol had higher unbound concentrations in the ELF compared to the plasma whilst this was not the case for the other compounds. Experiments with different BAL volumes and repeated lavaging indicated that the amount of drug extracted is very sensitive to experimental procedure. In addition, the results show that the unbound concentrations in ELF compared to plasma differs dependent on molecule class and tissue distribution properties. Overall data suggests that lavaging can remove drug from lung tissue in addition to ELF and highlights significant uncertainty in the robustness of the procedure for determining ELF drug concentrations. (c) 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
|
|
