Mechanism of Action of Hindered Amines as Long-Term Heat Stabilizer

2007 ◽  
pp. 48-58 ◽  
Author(s):  
Pieter Gijsman ◽  
Mikael Hamskog
Keyword(s):  
Mechanism Of Action ◽  
Heat Stabilizer ◽  
Hindered Amines

scholarly journals Severe Posaconazole-Induced Glucocorticoid Deficiency with Concurrent Pseudohyperaldosteronism: An Unfortunate Two-for-One Special

2021 ◽  
Vol 7 (8) ◽  
pp. 620
Author(s):  
Alejandro Villar-Prados ◽  
Julia J. Chang ◽  
David A. Stevens ◽  
Gary K. Schoolnik ◽  
Samantha X. Y. Wang
Keyword(s):  
Mechanism Of Action ◽  
Antifungal Agents ◽  
Laboratory Findings ◽  
Steroid Synthesis ◽  
Adrenal Steroid ◽  
History Of ◽  
Glucocorticoid Deficiency

A 56-year-old Hispanic man with a history of disseminated coccidioidomycosis was diagnosed with persistent glucocorticoid insufficiency and pseudohyperaldosteronism secondary to posaconazole toxicity. This case was notable for unexpected laboratory findings of both pseudohyperaldosteronism and severe glucocorticoid deficiency due to posaconazole’s mechanism of action on the adrenal steroid synthesis pathway. Transitioning to fluconazole and starting hydrocortisone resolved the hypokalemia but not his glucocorticoid deficiency. This case highlights the importance of recognizing iatrogenic glucocorticoid deficiency with azole antifungal agents and potential long term sequalae.

scholarly journals Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world

2017 ◽  
Vol 10 (10) ◽  
pp. 343-359 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Katja Thomas
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Real World ◽  
Continuous Treatment ◽  
The Real ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.

Mod-5014, a Long-Acting FVIIa-CTP, Proposing a Novel Prophylactic Treatment Supporting Less Frequent Subcutaneous or Intravenous Injections with a Similar Mechanism of Action to rFVIIa: Proof-of-Concept in Hemophilic Animal Models

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4670-4670 ◽  
Author(s):  
Lior Binder ◽  
Ahuva Bar-Ilan ◽  
Malka Hoffman ◽  
Gili Hart
Keyword(s):  
Mechanism Of Action ◽  
Half Life ◽  
Prophylactic Treatment ◽  
Conflicts Of Interest ◽  
Clinical Stage ◽  
Routes Of Administration ◽  
Hemostatic Effect ◽  
Long Acting

Abstract Introduction: OPKO Biologics is a clinical-stage public company developing bio-better long-acting versions of existing therapeutic proteins, utilizing a technology termed CTP. The technology involves fusion of the C-terminal peptide of hCG to a target protein. The aim of this work was to comprehensively assess the feasibility of intravenous (IV) or subcutaneous (SC) administration of FVIIa-CTP (MOD-5014) utilizing the most relevant in vivo pre-clinical models, and to characterize the FVIIa-CTP mechanism of action in preparation for an on-going clinical study. Methods: FVII-CTP was expressed in CHO cells, purified and activated utilizing a CTP-specific purification process. FVIIa-CTP's pharmacokinetics (PK), pharmacodynamics (PD), long-term hemostatic effect and safety parameters were extensively characterized following SC and IV administration in transient FVII-/- rats and FVIII-/- mice. In addition, the long-term hemostatic effect of FVIIa-CTP was evaluated following a bleeding challenge and compared to commercial rFVIIa. Finally, interaction with co-factors, activity, and the off-target effect of FVIIa-CTP was comprehensively characterized. Results: The studies demonstrated that FVIIa-CTP provides long-term exposure (AUC) and half-life that are significantly superior to those of rFVIIa, and consistent with the prolonged half-life of FVIIa-CTP (at an average of 3- and 5-fold, respectively) when compared to IV or SC administration of FVIIa. In addition, a 30% increase in bioavailability was observed relative to commercial FVIIa. A profound improvement in clotting parameters and survival rate following TVT, as well as a reduction of bleeding duration and intensity in tail-clip studies were obtained for both routes of administration for up to 48 hours. Moreover, the safety profile of FVIIa-CTP was further confirmed. Conclusion: Attachments of CTP to FVIIa led to a pronounced enhancement of PK and PD, increased exposure as reflected by AUC, elevated half-life, and improved recovery in mice, rats and pigs following SC and IV administration. FVIIa-CTP injection resulted in an improved bioavailability that translated to a marked in vivo hemostatic effect. Our data suggest that CTP-fused FVIIa can potentially provide a novel approach for IV or SC prophylactic treatment of hemophilic patients (both pediatric and adult), with the major benefit of significant improvement in quality of life. Disclosures No relevant conflicts of interest to declare.

A NOVEL IMMUNOSUPPRESSANT, FTY720, WITH A UNIQUE MECHANISM OF ACTION, INDUCES LONG-TERM GRAFT ACCEPTANCE IN RAT AND DOG ALLOTRANSPLANTATION1

1996 ◽  
Vol 61 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Seiichi Suzuki ◽  
Shin Enosawa ◽  
Toshihiro Kakefuda ◽  
Takahisa Shinomiya ◽  
Masao Amari ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Unique Mechanism

scholarly journals Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice

2017 ◽  
Vol 114 (15) ◽  
pp. E3110-E3118 ◽  
Author(s):  
Moustafa R. K. Ali ◽  
Mohammad Aminur Rahman ◽  
Yue Wu ◽  
Tiegang Han ◽  
Xianghong Peng ◽  
...  
Keyword(s):  
Cell Death ◽  
Mechanism Of Action ◽  
Gold Nanorods ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Infrared Light ◽  
Mouse Tumor ◽  
Maximal Induction

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm2) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome c and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.

scholarly journals Evolutionary Ecology of Prokaryotic Immune Mechanisms

2016 ◽  
Vol 80 (3) ◽  
pp. 745-763 ◽  
Author(s):  
Stineke van Houte ◽  
Angus Buckling ◽  
Edze R. Westra
Keyword(s):  
Mechanism Of Action ◽  
Evolutionary Ecology ◽  
Costs And Benefits ◽  
Defense Strategies ◽  
Ecological Conditions ◽  
Genetic Elements ◽  
Immune Mechanisms ◽  
Resistance Strategies ◽  
Short And Long Term

SUMMARYBacteria have a range of distinct immune strategies that provide protection against bacteriophage (phage) infections. While much has been learned about the mechanism of action of these defense strategies, it is less clear why such diversity in defense strategies has evolved. In this review, we discuss the short- and long-term costs and benefits of the different resistance strategies and, hence, the ecological conditions that are likely to favor the different strategies alone and in combination. Finally, we discuss some of the broader consequences, beyond resistance to phage and other genetic elements, resulting from the operation of different immune strategies.

Long Term Azithromycin in Cystic Fibrosis: Another Possible Mechanism of Action?

2005 ◽  
Vol 17 (4) ◽  
pp. 393-400 ◽  
Author(s):  
U. Pradal ◽  
A. Delmarco ◽  
M. Morganti ◽  
M. Cipolli ◽  
E. Mini ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mechanism Of Action

scholarly journals Osteoarthritis background therapy: current view on the glucosamine and chondroitin therapy

2021 ◽  
Vol 15 (2) ◽  
pp. 112-119
Author(s):  
L. I. Alekseeva ◽  
A. M. Lila
Keyword(s):  
Combination Therapy ◽  
Chondroitin Sulfate ◽  
Mechanism Of Action ◽  
Clinical Studies ◽  
Current Status ◽  
Current View ◽  
Background Therapy ◽  
Therapeutic Doses

The article highlights the current status of symptomatic slow-acting drugs (SYSADOA) in osteoarthritis (OA). Mechanism of action, clinical studies data on the effectiveness of glucosamine (GA) and chondroitin sulfate (CS) and their combinations in OA, their positive symptomatic and structural-modifying effects, are described. The article provides the latest recommendations for the OA treatment with these two drugs and presents an argument for the combination therapy with both drugs as a background therapy in the earliest stages of OA. It is indicated that such therapy should be long-term due to its high safety and possible reduction of cardiovascular accidents risk as well. It is noted that therapeutic doses of CS and GA are ≥1500 and ≥800 mg per day, respectively, and encapsulated forms of SYSADOAs have advantages due to their pharmacokinetic features.

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