Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger... Show moreGlucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment [6-11]. Therefore, developing novel strategies to improve the treatment inflammatory and immune conditions becomes urgent. Here, we present evidence that ginsenosides act as selective GR agonists, antagonists, and prodrugs. Moreover, our data illustrate that the number and positions of glucose groups bound to the steroid backbone of ginsenosides and different chemical structures are essential factors underlying the differential mechanistic effects of ginsenosides. Understanding the molecular mechanisms and the effects of natural compound (ginsenosides) opens a novel road towards developing improved anti-inflammatory GCs. Attaching one glucose group to classical GCs produced selective Gr agonists, such as GDex and GPdn, which exert anti-inflammatory effects without triggering side effects due to the absence of GR transactivation activities. Attaching two glucose groups to classical GCs resulted in the creation of GC prodrugs, such as GbPdn, which mediates its action locally at the site of inflammation, dependent on GBA2 activity, without triggering side effects. Show less
Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was... Show morePyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG. Show less
Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was... Show morePyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG.(c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
The COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of... Show moreThe COVID-19 pandemic has galvanized the global response towards the development of new vaccines based on novel technologies at an unprecedented pace. Since the widespread implementation of vaccination campaigns, case reports on vaccines' systemic side effects, including ocular manifestations, have emerged. Since administered vaccines are generally not able to cause the disease in the recipient, or induce an immune response against the pathogen, we hypothesize that the development of ocular phenomena post-COVID-19 vaccination may occur via an immune response elicited by the vaccine. Of many, the most common ocular adverse events include facial nerve palsy, central venous sinus thrombosis and acute anterior uveitis. These COVID-19 vaccine-induced ocular (CVIO) adverse events could resemble the ocular findings in some of the COVID-19 patients. This review will provide a comprehensive overview of published ocular side effects potentially associated with COVID-19 vaccination and serve as a springboard for further research into CVIO adverse events. Show less
Door de toepassing van hoofdhuidkoeling kan haaruitval worden verminderd of voorkomen. Hoofdhuidkoeling heeft, afhankelijk van de soort chemotherapie, bij ongeveer 50% van de patiënten een positief... Show moreDoor de toepassing van hoofdhuidkoeling kan haaruitval worden verminderd of voorkomen. Hoofdhuidkoeling heeft, afhankelijk van de soort chemotherapie, bij ongeveer 50% van de patiënten een positief effect. Farmacologische interventies om haaruitval te voorkomen zijn niet toereikend. De incidentie van haaruitval kan verminderd worden door de methode van hoofdhuidkoeling te optimaliseren.De afgelopen jaren is door het Leids Universitair Medisch Centrum, Noordwest Ziekenhuisgoep en Integraal Kankercentrum Nederland in samenwerking met verschillende ziekenhuizen in Nederland onderzoek verricht naar factoren die van invloed kunnen zijn op het effect van hoofdhuidkoeling. Show less
Background Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often... Show moreBackground Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found. To address this need, this article proposes an innovative research approach based on pharmacological conditioning, to reduce MTX intolerance. Presentation of the hypothesis A collaboration between medical psychologists, pediatric rheumatologists, pharmacologists and patient groups was set up to develop an innovative research design that may be implemented to study potential improved control of side effects in JIA, by making use of the psychobiological principles of pharmacological conditioning. In pharmacological conditioning designs, learned positive associations from drug therapies (conditioning effects) are integrated in regular treatment regimens to maximize treatment outcomes. Medication regimens with immunosuppressant drugs that made use of pharmacological conditioning principles have been shown to lead to optimized therapeutic effects with reduced drug dosing, which might ultimately cause a reduction in side effects. Testing the hypothesis This research design is tailored to serve the needs of the JIA patient group. We developed a research design in collaboration with an interdisciplinary research group consisting of patient representatives, pediatric rheumatologists, pharmacologists, and medical psychologists. Show less
In the thesis I present a series of studies that focus on the use and optimization of use of low-dose ketamine in clinical practice by:(1) reviewing the proof for its use in alleviation and... Show moreIn the thesis I present a series of studies that focus on the use and optimization of use of low-dose ketamine in clinical practice by:(1) reviewing the proof for its use in alleviation and prevention of acute and chronic (cancer and non-cancer) pain;(2) testing a possible novel administration route of ketamine, i.e. inhalation;(3) applying ketamine in a novel indication: the use of the S-enantiomer as respiratory stimulant during opioid-induced respiratory depression;(4) studying the effect of a nitric oxide donor on ketamine (the racemic and S-ketamine variants) typical side effects that hamper it’s use in chronic pain therapy Show less
This thesis focuses on targeted anticancer agents. An important class of these agents are the tyrosine kinase inhibitors (TKIs). One of the first steps in TKI treatment development is defining... Show moreThis thesis focuses on targeted anticancer agents. An important class of these agents are the tyrosine kinase inhibitors (TKIs). One of the first steps in TKI treatment development is defining whether a specific type of cancer, for example the sarcomas in chapter 3 of this thesis, express the receptors that are targeted. Once a TKI is developed, phase I studies are conducted to characterize the safety and side effects of the drug when administered to patients. When relevant side effects emerge, studies investigating the underlying mechanisms leading to these side effects are called for. Also pharmacogenetic studies can be performed to investigate whether certain heritable genetic variations influence efficacy or safety of the drug. After the phase I studies have proven the drug to be safe, the drug can be further developed. This includes the investigation of the TKI when combined with other anticancer agents. Items of all the described steps in TKI development are described in this thesis. Show less
