58 research outputs found

    A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

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    This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

    Morally Evaluating Human Smuggling: The Case of Migration to Europe

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    Much of the recent debate on immigration to Europe has focused on how many refugees should be allowed to enter and how refugees should be distributed among EU member states, but there has been less academic focus on under what conditions, if any, human smuggling is morally permissible. How should we morally assess those who make a business out of helping migrants reach their desired destination and those who pay smugglers to reach their destination? We argue that human smuggling is morally permissible under some conditions even if it is illegal. Human trafficking, by contrast, is immoral and should be illegal. The moral conditions for permissible human smuggling are sometimes being met on the route from Africa to Europe (but are all too often grossly violated). We consider and rebut objections based on the arguments that a legal prohibition on human smuggling must translate into a moral one, and that human smuggling violates the rights of individuals to freedom of association in receiving countries. We conclude with policy implications.Security and Global Affair

    Antibiotic susceptibility of Staphylococcus aureus in suppurative lesions in Lacor Hospital, Uganda

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    Background: Staphylococcus aureus , a mainly acquired hospital infection is responsible for many suppurative lesions and has demonstrated the ability of developing resistance to many antimicrobial agents leading to life threatening infections and long hospital stay. Objective: To determined the prevalence and antibiotic susceptibility of Staphylococcus aureus in suppurative lesions of the surgical ward and outpatients of Lacor Hospital (Uganda). Methods: A cross-sectional study was conducted at St. Mary’s Hospital Lacor to determine the prevalence and antibiotic susceptibility profiles of Staphylococcus aureus in suppurative lesions in both surgical inpatients and outpatients. Using culture techniques on MacConkey and blood agar, Staphylococcus aureus was isolated based on the colonial characteristics and confirmed by Catalase and tube Coagulase tests. The antibiotic susceptibility test was done using Kirby-Buer disk diffusion method on 4% Salt Muellar Hinton II agar for the Methicillin and non salted Muellar Hinton II agar for the other antibiotics (NCCLS M100S9). Results: The prevalence of Staphylococcus aureus in 122 patients sampled was 59.4% for the surgical inpatients and 48.3% for outpatients giving an average prevalence of 53.9% for both groups of patients. The average antibiotic susceptibility patterns for the 8 antibiotic tested were: Ampicillin (75.0%), Chloramphenicol (34.4%), Ciprofloxacin (1.6%), Erythromycin (7.8%), Gentamycin (0%), Methicillin (1.6%), Tetracycline (45.3%) and Co-trimoxazole (50.0%). The resistance in surgical inpatients was significantly higher than outpatients (t=1299, p<0.05) and Methicillin resistance was confirmed by PCR. Conclusion: Staphylococcus aureus is highly prevalent and more resistant in inpatients. There is a higher risk of acquiring drug resistant staphylococcus aureus infection in inpatients of Lacor Hospital with a Methicillin resistance of 0% and 2.6% for out and inpatients respectively
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