Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Apr 2019
Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database.
Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. ⋯ Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.
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Fundam Clin Pharmacol · Aug 2016
Levobupivacaine attenuates lipopolysaccharide-induced acute lung injury.
Levobupivacaine (LB), a kind of local anesthetic, possesses anti-inflammatory properties. High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of acute lung injury (ALI). The aim of this study was to investigate whether LB attenuates ALI by the inhibition of HMGB1 expression and to investigate the molecular mechanisms. ⋯ Furthermore, LB significantly inhibited LPS-induced TLR2/4 protein overexpression and NF-κB activation in the lung tissues and in LPS-stimulated A549 alveolar epithelial cells in vitro. These data indicate that LB attenuated LPS-induced ALI by the inhibition of HMGB1 expression in rats. These benefits were associated with the inhibition of TLR2/4-NF-κB pathway by LB.
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Fundam Clin Pharmacol · Feb 2016
Randomized Controlled TrialEfficacy of nebulized L-epinephrine for treatment of croup: a randomized, double-blind study.
The objective of this study was to compare the effect of L-epinephrine plus dexamethasone vs. dexamethasone for treatment of croup in children. A randomized, double-blind clinical trial was implemented on 174 patients with croup, aged from 6 months to 6 years, and admitted to the Amir Kabir Pediatric Hospital (Arak, Iran). After randomized allocation, patients were administered dexamethasone, and then, they received either saline or L-epinephrine. ⋯ There was a significant difference in mean of croup scores between two groups (P < 0.009). In addition, a significant difference was seen on mean of heart rate between two groups (P < 0.026). Our results showed a considerable difference in reduction of velocity of croup scores in patients who received nebulized L-epinephrine compared to patients who received placebo.
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Fundam Clin Pharmacol · Dec 2015
Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.
Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. ⋯ Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade.
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Fundam Clin Pharmacol · Oct 2015
Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?
Accidental intravascular or high-dose injection of local anesthetics (LA) can result in serious, potentially life-threatening complications. Indeed, adequate supportive measures and the administration of lipid emulsions are required in such complications. The study's objectives were threefold: (i) evaluate the myocardial toxicity of levobupivacaine when administered intravenously; (ii) investigate levobupivacaine toxicity on cardiomyocytes mitochondrial functions and cellular structure; (iii) assess the protective effects of a lipid emulsion in the presence or absence of myocardial ischemia. ⋯ Myocardial ischemia was associated with global worsening of all changes. Intralipid(®) quickly improved haemodynamics. However, beneficial effects of Intralipid(®) were less clear after myocardial ischemia.