PubMed · 13004579
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E CARPENTIER. 1952-09-15. [Cutaneous tuberculosis].. https://pubmed.ncbi.nlm.nih.gov/13004579/
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The magnitude and duration of CD8(+) T cell-mediated responses in the skin to hapten sensitization and challenge, contact hypersensitivity (CHS), is negatively regulated by CD4(+) T cells through an unknown mechanism. In this study we show that CD4(+) T cells restrict the development and expansion of hapten-specific CD8(+) T cells mediating CHS responses to 2,4-dinitrofluorobenzene. In the absence of CD4(+) T cells, high numbers of hapten-specific CD8(+) T cells producing IFN-gamma were detected in the skin-draining lymph nodes on day 5 postsensitization, and these numbers decreased slightly, but were maintained through day 9, correlating with the increased magnitude and duration of CHS responses observed in these mice. In the presence of CD4(+) T cells, the number of hapten-specific CD8(+) T cells producing IFN-gamma detected on day 5 postsensitization was lower and quickly fell to background levels by day 7. The limited development of effector CD8(+) T cells was associated with decreased numbers of hapten-presenting dendritic cells in the lymphoid priming site. This form of immunoregulation was absent after sensitization of Fas ligand-defective gld mice. Transfer of wild-type CD4(+) T cells to gld mice restored the negative regulation of CD8(+) T cell priming and the immune response to hapten challenge in gld-recipient mice. These results indicate that CD4(+) T cells restrict hapten-specific CD8(+) T cell priming for CHS responses through a Fas ligand-dependent mechanism.
We report on a 30 year-old male who misused transdermal fentanyl. He injected the contents of transdermal patches intravenously. Suffering from chronic pain following total hip replacement, he had received a prescription for this drug formulation from his general practitioner. During his stay in a pain clinic he was able to obtain a total of 13 fentanyl patches from other patients or local pharmacies. He became seriously ill with multiple organ dysfunction in the course of an infection of his thigh. After surgical and intensive care treatment he recovered soon, but the hip prosthesis had to be explanted. There are some reports in the literature of misuse of fentanyl patches. The contents may be ingested orally, or they can be inhaled. Aspirated with a syringe the content of fentanyl patches can also be injected intravenously, sometimes resulting in exit-us. Prescribers must be aware of the potential for abuse of fentanyl patches which can be stolen, sold or even removed from dead bodies.
The development of a transdermal delivery system for isosorbide dinitrate (ISDN) using electron beam irradiation was studied. The solid state stability of the drug to irradiation was assessed. The drug was dissolved in 2-ethylhexylacrylate (EHA)-acrylic acid (AA) system and this solution was directly irradiated on a backing membrane (Scotchpak1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratios (EWSR), differential scanning calorimetry (DSC), weight uniformity, thickness uniformity, drug content and content uniformity, peel strength, in vitro release, skin permeation kinetics and skin irritation potential. The developed system possessed excellent adhesive properties. Increase in the irradiation doses did not have a significant effect on the peel strength values. The systems exhibited promising skin permeation kinetics and no skin irritating potential, both of which are important properties for transdermal drug delivery. The ISDN-EHA-AA system developed at an irradiation dose of 50 kGy showed a higher skin permeation profile as compared to an internationally marketed transdermal matrix system of ISDN.