Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Oct 2011
ReviewDoping and musculoskeletal system: short-term and long-lasting effects of doping agents.
Doping is a problem that has plagued the world of competition and sports for ages. Even before the dawn of Olympic history in ancient Greece, competitors have looked for artificial means to improve athletic performance. Since ancient times, athletes have attempted to gain an unfair competitive advantage through the use of doping substances. ⋯ Apart from the unethical aspect of doping, as it abrogates fair-play's principle, it is extremely important to consider the hazards it presents to the health and well-being of athletes. The referred negative effects for the athlete's health have to do, on the one hand, by the high doses of the performance-enhancing agents and on the other hand, by the relentless, superhuman strict training that the elite or amateur athletes put their muscles, bones, and joints. The purpose of this article is to highlight the early and the long-lasting consequences of the doping abuse on bone and muscle metabolism.
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Fundam Clin Pharmacol · Oct 2011
Evidence of clonazepam abuse liability: results of the tools developed by the French Centers for Evaluation and Information on Pharmacodependence (CEIP) network.
Recent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. ⋯ Studies based on data from the French health reimbursed system show that 1.5% of subjects with clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the second most important doctor-shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of clonazepam abuse liability in real life and the necessity to reinforce its monitoring.
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Fundam Clin Pharmacol · Oct 2011
Effects of florfenicol on LPS-induced nitric oxide and prostaglandin E₂ production in RAW 264.7 macrophages.
Florfenicol, an antibiotic commonly used to treat infections, has previously been shown to modulate lipopolysaccharide (LPS)-induced early cytokine responses by blocking the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the effects of florfenicol on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production as well as on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated murine RAW 264.7 macrophages. We also analysed the effects of florfenicol on mitogen-activated protein kinase (MAPK) pathways. ⋯ However, c-Jun N-terminal kinase (JNK) phosphorylation remained unaffected. Using specific inhibitors of ERK and p38, we found that florfenicol may inhibit NO and PGE₂ mostly through ERK and p38 pathway. These results suggest that florfenicol inhibits NO and PGE₂ production in conjunction with an inhibition of iNOS and COX-2 expression, at least partially via suppression of ERK1/2 and p38 MAPK phosphorylation.
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Fundam Clin Pharmacol · Aug 2011
ReviewSurrogate endpoints in randomized cardiovascular clinical trials.
Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. ⋯ Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints.
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Fundam Clin Pharmacol · Aug 2011
Clinical TrialRelationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period.
Although intravenous morphine titration (IMT) is widely used to control moderate to severe postoperative pain, the relationships between plasma concentrations of morphine and its metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), and IMT outcomes in the postanesthesia care unit (PACU) have not been yet investigated. IMT was administrated as a bolus of 2 or 3 mg every 5 min. Titration was interrupted in case of pain relief (visual analog score ≤30), adverse events, sedation, or failure of morphine titration. ⋯ At the end of titration, there were no significant differences in morphine, M6G, M3G concentrations between sedated and nonsedated patients (32 vs. 42 ng/mL (P = 0.07), 38 vs. 45 ng/mL (P = 0.51), 300 vs. 342 ng/mL (P = 0.29), respectively), or patients with or without adverse events (40 vs. 41 ng/mL (P = 0.95), 37 vs. 46 ng/mL (P = 0.51), 287 vs. 340 ng/mL (P = 0.72), respectively). Our study demonstrated a lack of relationship between plasma concentrations or ratios of morphine, M3G, and M6G, with IMT outcomes in PACU. This result suggests that the kinetics of morphine and its metabolites have limited value for explaining clinical effects of morphine in this clinical setting.