Dose/time-dependent modulation of the endothelial function through immunosuppressive agents

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
I. Kanzler ◽  
N. Bogert ◽  
F. Guo ◽  
A. Moritz ◽  
A. Beiras-Fernandez
2014 ◽  
Vol 46 (9) ◽  
pp. 2953-2956 ◽  
Author(s):  
I. Werner ◽  
N.V. Bogert ◽  
U.A. Stock ◽  
A. Moritz ◽  
A. Beiras-Fernandez

Blood ◽  
1970 ◽  
Vol 36 (4) ◽  
pp. 458-469 ◽  
Author(s):  
MARKLEY H. BOYER ◽  
ANTONY BASTEN ◽  
PAUL B. BEESON

Abstract Intravenous inoculation of Trichinella larvae into rats is followed by eosinophilia with a peak at 6 days. Reinjection of the parasites 20 days later results in an enhanced eosinophil response. This phenomenon may be analogous to the anamnestic antibody response which follows reinjection of antigenic material. Various agents known to modify conventional expressions of immunity were tested for their abilities to influence both primary and secondary eosinophil responses. Given in low single doses, methotrexate and cyclophosphamide could suppress the eosinophil response only after larval challenge; busulfan, prednisolone, bacterial endotoxin, Corynebacterium anaerobium and pertussis vaccine were effective only before the inoculum of parasites. The time-dependent action of these agents on eosinophilia is similar to their action on other systems of immune expression. Of further interest was the observation that certain of the agents which were suppressant when given before first larval challenge also appeared to affect "priming" for the second response. Eosinophilia appears to share common features with recognized immune phenomena. The model described may be useful in studying the cellular kinetics of immune responses, the action of immunosuppressive agents and other problems of cell differentiation or proliferation.


2019 ◽  
Vol 105 (1) ◽  
pp. E104-E105
Author(s):  
S. Nagtegaal ◽  
S. David ◽  
M. Philippens ◽  
A. Leemans ◽  
J. Verhoeff

2017 ◽  
Vol 139 ◽  
pp. 76-88 ◽  
Author(s):  
Adejoke Y. Onaolapo ◽  
Olakunle J. Onaolapo ◽  
Polycarp U. Nwoha
Keyword(s):  

2013 ◽  
Vol 781-784 ◽  
pp. 1160-1163
Author(s):  
Xiong Zhang ◽  
Jie Yun Sun ◽  
Hong Mei Zhang ◽  
Lu Si ◽  
Yu Li

As a promising prevention and therapeutic intervention in Alzheimer’s disease, natural food dyes curcumin could obviously inhibit the generation of Aβ, but the mechanism is not fully defined. This study aims to investigate the effects of curcumin on the amyloidogenic pathway of APP in vitro. Plasmids APPswe and BACE1-mychis were transiently co-transfected into SH-SY5Y and HEK293 cells. Then, they were treated with curcumin at 0, 1.25, 5, 20 μmol/L for 24 h, or with curcumin at 5μmol/L for 0, 12, 24 and 48 h for the time course assay. Our findings showed that curcumin could inhibit the expression of the APP at mRNA level; the expression of the BACE1 and C99 at mRNA and protein levels, furthermore it could inhibit the generation of Aβ40/42, and those changes were dose-time dependent (p<0.05). Our study indicates that Aβ40/42 generation inhibition effect of curcumin might due to its influence on amyloidogenic pathway. This may provide important experimental basis for AD treatment with curcumin.


2019 ◽  
Vol 33 (6) ◽  
pp. 912-914 ◽  
Author(s):  
Jeremiah D. Momper ◽  
Jin Yang ◽  
Janice Kerr ◽  
Ila Saunders ◽  
Jennifer Smith ◽  
...  

Solid organ transplant recipients have increased cancer risk due in part to chronic immunosuppression and opportunistic oncogenic viral infections. The management of drug interactions in transplant recipients being treated for cancer is important both to minimize the likelihood of drug-related toxicities and to optimize therapeutic outcomes. We present a case of a 41-year-old woman with a stable living–related kidney transplant maintained on an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and prednisone, who was subsequently diagnosed with a metastatic lobular breast carcinoma and papillary thyroid cancer and started palbociclib, a time-dependent CYP3A inhibitor. After initiation of palbociclib, cyclosporine trough and peak concentrations were increased by 159% and 81%, respectively, relative to the average cyclosporine concentrations pre-palbociclib. Using the Drug Interaction Probability Scale (DIPS), the interaction between palbociclib and cyclosporine was rated as “probable.” Dose reductions of immunosuppressive agents that are CYP3A substrates are warranted if palbociclib is initiated, followed by close monitoring of blood concentrations. This report also highlights the challenges of coadministering a time-dependent inhibitor with a narrow therapeutic index drug that is metabolized by the same enzyme, particularly when the inhibitor is given in cycles with off-treatment periods.


2013 ◽  
Vol 11 (1) ◽  
pp. 100-106 ◽  
Author(s):  
M. U. ZAFAR ◽  
C. SANTOS-GALLEGO ◽  
D. A. VORCHHEIMER ◽  
J. F. VILES-GONZALEZ ◽  
S. ELMARIAH ◽  
...  

2014 ◽  
Vol 55 (5) ◽  
pp. 1005-1016 ◽  
Author(s):  
Hilary S. Ireland ◽  
Kularajathevan Gunaseelan ◽  
Ratnasiri Muddumage ◽  
Emma J. Tacken ◽  
Jo Putterill ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1520-1526
Author(s):  
Mauricio Concha ◽  
Alexander T. Cohen

Intracerebral bleeds related to anticoagulant use have a poor prognosis and substantial risk of disability and death. Recent publications evaluating replacement or reversal therapies for anticoagulants lack consistency in controlling for key factors that significantly influence outcomes. In an effort to guide future research by providing a framework to improve consistency and reduce the potential for confounding in this dynamic and highly time-dependent brain insult, we provide here a brief overview of variables we consider critical in studies evaluating the risk and the reversal of anticoagulant therapies in anticoagulant-related intracerebral bleeds. Hematoma expansion stands out as one of the few potentially modifiable risk factors and its early control could mitigate secondary brain injury, and it, therefore, requires careful categorization. In addition to the baseline demographic, clinical, and radiological predictors of hematoma expansion, we specifically highlight time-dependent factors such as the time from the last dose, time from symptom onset and time to treatment, the computed tomography angiography spot sign, and the limitation of early care as especially critical predictors of outcomes in anticoagulant-related intracerebral bleeds. Intracerebral hemorrhage is a condition that requires fast diagnosis and treatment, especially when associated with anticoagulants. The advent of therapies with rapid reversal of anticoagulation open the opportunity to assess the scale to which faster reversal of anticoagulation modifies hematoma expansion and clinical outcomes. Thus, comprehensive assessment and reporting of these important potential confounding factors, particularly the critical time variables, is crucial to improving research and treatment of intracerebral hemorrhages.


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