scholarly journals Inhibition of keratinocyte proliferation by phospholipid-conjugates of a TLR7 ligand in a Myc-induced hyperplastic actinic keratosis model in the absence of systemic side effects

2013 ◽  
Vol 23 (5) ◽  
pp. 618-628 ◽  
Author(s):  
Brian Crain ◽  
Shiyin Yao ◽  
Vina Keophilaone ◽  
Victor Promessi ◽  
McNancy Kang ◽  
...  
Keyword(s):  
Side Effects ◽  
Actinic Keratosis ◽  
Keratinocyte Proliferation ◽  
Systemic Side Effects ◽  
Tlr7 Ligand

scholarly journals Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2138 ◽  
Author(s):  
Takumi Satoh ◽  
Stuart Lipton
Keyword(s):  
Side Effects ◽  
Specific Interaction ◽  
Dimethyl Fumarate ◽  
Carnosic Acid ◽  
European Medicines Agency ◽  
Related Factor ◽  
Inflammatory Phase ◽  
First Case ◽  
Systemic Side Effects ◽  
Transcriptional Pathway

Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera®. It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcriptional pathway that induces anti-oxidant and anti-inflammatory phase II enzymes to prevent chronic neurodegeneration. However, electrophiles such as DMF also produce severe systemic side effects, in part due to non-specific S-alkylation of cysteine thiols and resulting depletion of glutathione. This mini-review presents the present status and future strategy for NRF2 activators designed to avoid these side effects. Two modes of chemical reaction leading to NRF2 activation are considered here. The first mode is S-alkylation (covalent reaction) of thiols in Kelch-like ECH-associated protein 1 (KEAP1), which interacts with NRF2. The second mechanism involves non-covalent pharmacological inhibition of protein-protein interactions, in particular domain-specific interaction between NRF2 and KEAP1 or other repressor proteins involved in this transcriptional pathway. There have been significant advances in drug development using both of these mechanisms that can potentially avoid the systemic side effects of electrophilic compounds. In the first case concerning covalent reaction with KEAP1, monomethyl fumarate and monoethyl fumarate appear to represent safer derivatives of DMF. In a second approach, pro-electrophilic drugs, such as carnosic acid from the herb Rosmarinus officinalis, can be used as a safe pro-drug of an electrophilic compound. Concerning non-covalent activation of NRF2, drugs are being developed that interfere with the direct interaction of KEAP1-NRF2 or inhibit BTB domain and CNC homolog 1 (BACH1), which is a transcriptional repressor of the promoter where NRF2 binds.

Efficacy of ultra-low-dose (0.1 mg) ranibizumab intravitreal injection for treatment of prethreshold type 1 retinopathy of prematurity: A case series

2018 ◽  
Vol 30 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Islam SH Ahmed ◽  
Ahmed MA Hadi ◽  
Hassan H Hassan
Keyword(s):  
Side Effects ◽  
Intravitreal Injection ◽  
Retinopathy Of Prematurity ◽  
Large Scale ◽  
Low Dose ◽  
Case Series ◽  
Results Of Treatment ◽  
Case Series Study ◽  
Systemic Side Effects

Aim: To report the results of treatment of type 1 prethreshold retinopathy of prematurity using intravitreal injection of ultra-low dose of ranibizumab (0.1 mg in 0.01 mL). Design: A retrospective observational case series study. Methods: Review of files of eligible infants who received this form of treatment to determine the outcome of treatment and any associated ocular or systemic side effects. Results: The study included 24 eyes of 12 preterm infants with mean gestational age of 29.75 ± 1.54 weeks and mean birth weight of 1074.58 ± 320.59 g. A total of 22 eyes (91.67%) had zone II disease while 2 eyes of one infant (8.33%) had zone I disease. All cases showed regression of the signs of the active retinopathy of prematurity with complete retinal vascularization. None of the cases required retreatment. Three eyes developed ocular complications. Apart from mild feeding intolerance that lasted for 24 h after injection in one infant, none of the cases developed systemic side effects. Conclusion: Intravitreal injection of ultra-low-dose ranibizumab showed promising efficacy and good ocular safety. However, further large-scale studies are required to give stronger evidence about the efficacy and safety of ultra-low-dose ranibizumab.

Immunoengineering approaches for cytokine therapy

2021 ◽  
Author(s):  
Aslan Mansurov ◽  
Abigail Lauterbach ◽  
Erica Budina ◽  
Aaron T. Alpar ◽  
Jeffrey A. Hubbell ◽  
...  
Keyword(s):  
Side Effects ◽  
Protein Engineering ◽  
Autoimmune Diseases ◽  
Inflammatory Cytokines ◽  
Therapeutic Efficacy ◽  
Cytokine Therapy ◽  
Toxicity Profile ◽  
Wild Type ◽  
Systemic Side Effects ◽  
Secondary Lymphoid Organs

Since the discovery of cytokines, much effort has been put forth to achieve therapeutic translation for treatment of various diseases, including cancer and autoimmune diseases. Despite these efforts, very few cytokines have cleared regulatory approval, and those that were approved are not commonly used due to their challenging toxicity profile and/or limited therapeutic efficacy. The main limitation in translation has been that wild-type cytokines have unfavorable pharmacokinetic and pharmacodynamic profiles, either eliciting unwanted systemic side effects or insufficient residence in secondary lymphoid organs. In this review, we address protein engineering approaches that have been applied to both pro- and anti-inflammatory cytokines to enhance their therapeutic indices, and we highlight diseases in which administration of engineered cytokines is especially relevant.

The Use and Abuse of Topical Corticosteroids

1977 ◽  
Vol 63 (1) ◽  
pp. 18-25
Author(s):  
M. D. Catterall
Keyword(s):  
Side Effects ◽  
Topical Corticosteroid ◽  
Corticosteroid Therapy ◽  
Rank Order ◽  
Topical Corticosteroids ◽  
Systemic Side Effects

AbstractA rationalised approach to topical corticosteroid therapy is presented. Factors which influence the choice of preparation are considered, based upon the concept of ’rank order ’, for both halogenated and non-halogenated steroids. Practical considerations, including choice of base, polythene occlusion and tachyphylaxis are discussed and local and systemic side effects considered in detail.

"Topical Steroid Holiday"

PEDIATRICS ◽  
1995 ◽  
Vol 95 (3) ◽  
pp. 455-456
Author(s):  
David Hepburn ◽  
Joseph Morelli ◽  
William L. Weston
Keyword(s):  
Side Effects ◽  
Plasma Cortisol ◽  
Topical Steroid ◽  
Topical Steroids ◽  
Prescribing Pattern ◽  
Biphasic Pattern ◽  
Systemic Side Effects ◽  
Continued Use ◽  
Cortisol Levels ◽  
Pediatric Prescribing

Daily use of low-potency topical steroids is a frequently observed pediatric prescribing pattern.1 Many clinicians believe such a strategy is safe because low-potency topical steroids usually do not suppress levels of plasma cortisol or produce systemic side effects. However, daily use of low-potency steroids may result in suppression of plasma cortisol levels.1-4 Suppression of plasma cortisol levels after use of topical steroids has been observed in a biphasic pattern. There is suppression within 2 weeks of starting daily therapy, then recovery to normal despite continued use, then suppression again after 4 to 6 weeks of daily therapy.2,3

Topical anesthetics and analgesics

2021 ◽  
pp. 494-500
Author(s):  
William T. Zempsky
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Oral Administration ◽  
Topical Administration ◽  
Venous Access ◽  
Clinical Situation ◽  
Chronic Musculoskeletal Pain ◽  
Topical Anesthetics ◽  
Systemic Side Effects ◽  
Inflammatory Drugs

Topical administration of anesthetics and analgesics can allow for the efficient, painless delivery of medications that may reduce systemic side effects associated with the medication, whilst providing clinical advantages over injected or oral administration for the same clinical situation. Topical anesthetics have become widely used prior to a variety of painful procedures in children, including venous access, laceration repair, and injections. Topical administration of nonsteroidal anti-inflammatory drugs, lidocaine, capsaicin, and other agents also are useful for a range of conditions, including acute and chronic musculoskeletal pain, and neuropathic pain.

scholarly journals Safety evaluation of SPF66 malaria vaccine in Brazil

1996 ◽  
Vol 29 (5) ◽  
pp. 497-501 ◽  
Author(s):  
LM. Urdaneta ◽  
A. Prata ◽  
C.J. Struchiner ◽  
C.E. Tosta ◽  
P. Tauil ◽  
...  
Keyword(s):  
Placebo Group ◽  
Side Effects ◽  
Malaria Vaccine ◽  
Adverse Reactions ◽  
Safety Evaluation ◽  
Efficacy Trial ◽  
Systemic Side Effects ◽  
Local Reactions ◽  
Severe Adverse Reactions ◽  
Local Side

The frequency and description of side effects secondaiy to the subcutaneous application of SPf66 malaria vaccine and placebo are reported for each dose of application in the participants of the vaccine efficacy trial in Brazil. Side effects evaluated two hours after each application were detected in 8.0%, 30.2% and 8.8%, for the Is', and 3"' dose, respectively, in the SPf66group, and in 7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild inflammation, nodule and pain or erythema frequently accompanied by pruritus were the most common reactions detected in both groups (3-8%, 29.1% and 8.5% in the SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local side effects after the 2nd dose were more frequent in females. Systemic side effects were expressed mainly through general symptoms referred by the participants and were most frequent after the 1st dose in both groups (4.3% in the SPf66 group and 3-0% in the placebo group). Muscle aches and fever were refewred by few participants. No severe adverse reactions were detected for either dose of application or group.

scholarly journals Fluticasone Propionate in Inflammatory Bowel Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 417-419 ◽  
Author(s):  
Marta Carpani de Kaski ◽  
Humphery JF Hodgson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Long Term Treatment ◽  
Systemic Side Effects ◽  
Inflammatory Bowel

Although effective for both acute and often long term treatment of inflammatory bowel disease, systemically absorbed corticosteroids have a high incidence of side effects. This article briefly reviews the pharmacokinetics of corticosteroids and the strategics available for reducing systemic side effects. In particular, fluitcasone propionate is a fluorinated glucocorticoid, in which systemic side effects are absent or minimal due to its relatively low absorption and rapid first pass metabolism In an open trial in 12 patients with mild and moderately active Crohn's disease, administration of 20 mg fluitcasone propionate orally was associated with a significant fall in the Crohn's disease activity index and improvement in other parameters of inflammation, without change in either plasma cortisol levels or responsiveness to adrenocorticotropic hormone, suggesting that this drug is a promising therapy for Crohn's disease meriting evaluation against conventional corticosteroids.

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