Gelatin‐stabilised microemulsion‐based organogels facilitates percutaneous penetration of Cyclosporin A In Vitro and dermal pharmacokinetics In Vivo

2007 ◽  
Vol 96 (11) ◽  
pp. 3000-3009 ◽  
Author(s):  
Hongzhuo Liu ◽  
Yongjun Wang ◽  
Fei Han ◽  
Huimin Yao ◽  
Sanming Li
Keyword(s):  
Cyclosporin A ◽  
Percutaneous Penetration ◽  
Dermal Pharmacokinetics

Inhibition of Cyclosporin A-Induced Gingival Overgrowth by Azithromycin Through Phagocytosis: An In Vivo and In Vitro Study

2004 ◽  
Vol 75 (3) ◽  
pp. 380-387 ◽  
Author(s):  
Jeong-Won Paik ◽  
Chang-Sung Kim ◽  
Kyoo-Sung Cho ◽  
Jung-Kiu Chai ◽  
Chong-Kwan Kim ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
In Vitro Study ◽  
Vitro Study ◽  
Gingival Overgrowth

Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location

1993 ◽  
Vol 13 (8) ◽  
pp. 4760-4769
Author(s):  
R J Bram ◽  
D T Hung ◽  
P K Martin ◽  
S L Schreiber ◽  
G R Crabtree
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Cyclosporin A ◽  
Cell Function ◽  
Inhibitory Effects ◽  
Gene Deletions ◽  
Cyclophilin B ◽  
Intracellular Vesicles

The immunosuppressants cyclosporin A (CsA) and FK506 appear to block T-cell function by inhibiting the calcium-regulated phosphatase calcineurin. While multiple distinct intracellular receptors for these drugs (cyclophilins and FKBPs, collectively immunophilins) have been characterized, the functionally active ones have not been discerned. We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. In contrast, cyclophilin C, FKBP13, and FKBP25 had no effect. Direct comparison of the Ki of each drug-immunophilin complex for calcineurin in vitro revealed that although calcineurin binding was clearly necessary, it was not sufficient to explain the in vivo activity of the immunophilin. Subcellular localization was shown also to play a role, since gene deletions of cyclophilins B and C which changed their intracellular locations altered their activities significantly. Cyclophilin B has been shown previously to be located within calcium-containing intracellular vesicles; its ability to mediate CsA inhibition implies that certain components of the signal transduction machinery are also spatially restricted within the cell.

scholarly journals Partial inhibition by cyclosporin A of the swelling of liver mitochondria in vivo and in vitro induced by sub-micromolar [Ca2+], but not by butyrate. Evidence for two distinct swelling mechanisms

1990 ◽  
Vol 268 (1) ◽  
pp. 147-152 ◽  
Author(s):  
A M Davidson ◽  
A P Halestrap
Keyword(s):  
Light Scattering ◽  
Cyclosporin A ◽  
Binding Sites ◽  
Mitochondrial Protein ◽  
Liver Mitochondria ◽  
Partial Inhibition ◽  
Mitochondrial Volume ◽  
Bongkrekic Acid

1. The effects of cyclosporin A on the increase in matrix PPi and consequent swelling of energized liver mitochondria incubated with 1 mM-butyrate, 30 microM-bongkrekic acid or 0.1-35 microM-Ca2+ [Halestrap (1989) Biochim. Biophys. Acta 973, 355-382] were studied. 2. Cyclosporin (1 microM) had no significant effect on the swelling induced by butyrate, bongkrekic acid or Ca2+ at concentrations of less than 0.3 microM. 3. At higher [Ca2+] (greater than 0.3 microM), swelling became progressively inhibited by cyclosporin, although the increase in matrix PPi was slightly greater in the presence than in the absence of cyclosporin. 4. Titration with cyclosporin indicated that there are 128 pmol of relevant cyclosporin-binding sites per mg of mitochondrial protein, with a Ki of about 5 nM. 5. The decrease in light-scattering by hepatocytes induced by butyrate [Davidson & Halestrap (1988) Biochem. J. 254, 379-384] was unaffected by cyclosporin, whereas that induced by vasopressin was inhibited by 20-30% without a significant change in cellular PPi content. 6. It is suggested that there are two mechanisms for the increase in mitochondrial volume induced by Ca2+: a PPi-mediated mechanism that is insensitive to cyclosporin and an additional Ca2(+)-mediated effect that is inhibited by cyclosporin. The nature of these pathways and their inter-relationship is discussed in the following paper [Halestrap & Davidson (1990) Biochem. J. 268, 153-160].

scholarly journals Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 851-856 ◽  
Author(s):  
SA Burstein ◽  
SK Erb ◽  
JW Adamson ◽  
LA Harker
Keyword(s):  
Immune Response ◽  
Cyclosporin A ◽  
Progenitor Cells ◽  
Pokeweed Mitogen ◽  
Normal Rabbit Serum ◽  
Lymphocyte Function ◽  
Spleen Cells ◽  
Stimulation Of

Abstract Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies were assayed after injection of various heterosera or saline. All four colony types increased in the serum-treated groups. Since the in vitro proliferation of hematopoietic progenitor cells is promoted by supernatants of mitogen-stimulated spleen cells, we hypothesized that the immune response following antiserum administration resulted in the in vivo activation of T lymphocytes which produced or led to the production of colony stimulating activities. To test this hypothesis, cyclosporin A, a preferential inhibitor of T lymphocyte function, was given to mice concurrently with antiserum and also added to spleen cell cultures in the presence of pokeweed mitogen. Cyclosporin A abrogated the antiserum- related increases in progenitor cell numbers in vivo and the production of colony stimulating activity in vitro. The results suggest that the immune response related to antiserum administration results in the in vivo production of hematopoietic colony stimulating activities that may be identical to those produced in vitro by mitogen-stimulation of spleen cells.

Percutaneous Penetration of Nicotinates: In Vivo and In Vitro Measurements

1986 ◽  
Vol 75 (10) ◽  
pp. 968-972 ◽  
Author(s):  
Richard H.A. Guy ◽  
Eva M. Carlström ◽  
Daniel A.W. Bucks ◽  
Robert S. Hinz ◽  
Howard I. Maibach
Keyword(s):  
Percutaneous Penetration ◽  
In Vitro Measurements

scholarly journals In vivo and in vitro clonal deletion of double-positive thymocytes.

1992 ◽  
Vol 175 (5) ◽  
pp. 1307-1316 ◽  
Author(s):  
N J Vasquez ◽  
J Kaye ◽  
S M Hedrick
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytochrome C ◽  
Cyclosporin A ◽  
Negative Selection ◽  
Double Positive ◽  
Antigen Dose ◽  
Mhc Molecules

To study the processes of thymic development, we have established transgenic mice expressing and alpha/beta T cell antigen receptor (TCR) specific for cytochrome c associated with class II major histocompatibility complex (MHC) molecules. The transgenic TCR chains are expressed by most of the thymocytes in these mice, and these cells have been shown to efficiently mature in association with Ek- and Ab-encoded class II MHC molecules. This report describes a characterization of the negative selection of these transgenic thymocytes in vivo that is associated with the expression of As molecules. Negative selection by As molecules appears to result in the deletion of a late stage of CD4/CD8 double-positive thymocytes in that there is a virtual absence of transgenic TCR bearing CD4 single-positive thymocytes. This phenotype is accompanied by the appearance of CD4/CD8 double-negative thymocytes and peripheral T cells that are functionally antigen reactive. The process of negative selection has also been investigated using an in vitro culture system. Upon presentation of cytochrome c by Eb-expressing nonthymic antigen-presenting cells, there occurs an antigen dose-dependent deletion of the majority of CD4/CD8 double-positive thymocytes. In contrast, presentation of Staphylococcal enterotoxin A by Eb in vitro results in minimal deletion of double-positive thymocytes. In addition, we use this in vitro model to examine the effects of cyclosporin A on negative selection. In contrast to its effects on mature T cells, and the findings of others in vivo, cyclosporin A does not inhibit antigen-induced deletion of double-positive thymocytes. Finally, a comparison of the antigen dose responses for thymocyte deletion and for peripheral T cell activation indicates that double-positive thymocyte recognition is more sensitive than mature T cells to antigen recognition.

In vitro and in vivo correlation of cyclosporin A-induced apoptosis in acute lymphoblastic leukemia

2009 ◽  
Vol 63 (3) ◽  
pp. 207-209 ◽  
Author(s):  
O. Sezer ◽  
M. Schweigert ◽  
C. Naujokat ◽  
I. Mai ◽  
H-G. Mergenthaler ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cyclosporin A ◽  
Lymphoblastic Leukemia ◽  
Induced Apoptosis
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