The Golden Age of Medicine?
Roger Cooter, John Pickstone in Medicine in the Twentieth Century, 2020
Soon after scientists came to appreciate penicillin, soil biologist Selman Waksman and his colleagues identified another fungal agent, streptomycin, in 1943. This substance was demonstrated to be effective against tuberculosis first in animals, then in humans. Despite the dramatic success of streptomycin in many cases, some infections proved recalcitrant, and patients relapsed. The addition of new agents such as para-aminosalicylic acid (PAS) and isoniazid by the late 1940s offered the possibility of combination therapies which proved to be remarkably successful in treating tuberculosis. Antibiotic treatments for tuberculosis marked one of the great triumphs of twentieth-century medicine; tuberculosis, perhaps the most significant infection in world history, could now be decisively treated. Five years after the discovery of antibiotic therapy, many tuberculosis hospitals and sanatoria had closed; these structures now stood as historical monuments to the ‘golden age of medicine.’
Immunosuppressants, rheumatic and gastrointestinal topics
Evelyne Jacqz-Aigrain, Imti Choonara in Paediatric Clinical Pharmacology, 2021
The active ingredient in all aminosalicylates is 5 aminosalicylic acid (5-ASA). Sulfazalazine is a 5-ASA molecule and sulfapyridine acts as a carrier for 5-ASA. 5-ASA is released in the colon by bacterial cleavage. 5-ASA preparations are also available in three different prodrugs, in order to deliver 5-ASA to the distal gut. Olsalasine is two 5-ASA molecules with an azo bond, released in the colon by bacteria. Mesalazine is 5-ASA included in acrylic based resin, which breaks in the terminal ileum and colon releasing 5-ASA. Mesalamine is 5-ASA coated to a semi-permeable ethy 1-cellulose membrane, with a continuous release along the small intestine and colon [4]. The localisation of the disease will help determine the choice of treatment. 5-ASA is the active molecule and mainly inhibits leukotriene biosynthesis.
Inflammatory bowel disease
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Sulphasalazine 3g enemas result in a 70% response rate compared with 11% for placebo after 2 weeks’ of treatment in patients with proctitis and distal disease.10 Unlike oral treatment, topical sulphasalazine is well-tolerated, with no adverse effects. Sulphasalazine, however, is a bright orange-yellow in colour by virtue of its azo bond and may produce staining of underwear. Topical mesalazine, the active compound, is therefore the preferred form of treatment. Mesalazine suppositories, 500 mg twice daily, effectively induce remission in proctitis. In patients with distal disease, the efficacy and safety of 4 g 5-aminosalicylic acid (ASA) enemas (one nightly) was assessed over a 6-week study period by Sutherland et al.11 Treatment was well-tolerated and resulted in a response rate of 63% compared with 22% in the placebo group. A later study suggested that 1 g and 2 g enemas were equally effective as 4 g enemas when treating distal disease.12 Adverse effects of mesalazine enemas were rare and mild in these trials and comprised mainly of anal irritation. A retrospective study has shown an 80% remission rate after 34 weeks’ of treatment, suggesting that it is worth persisting in refractory disease.13
Manganese-induced neurodegenerative diseases and possible therapeutic approaches
Published in Expert Review of Neurotherapeutics, 2020
Airton C. Martins, Priscila Gubert, Gustavo R. Villas Boas, Marina Meirelles Paes, Abel Santamaría, Eunsook Lee, Alexey A. Tinkov, Aaron B. Bowman, Michael Aschner
The substance para-aminosalicylic acid (also known as PAS, 4-amino-2-hydroxybenzoic acid or 4-aminosalicylic acid) is used as antibacterial drug for treatment of tuberculosis [115]. PAS consists of carboxyl, hydroxyl and amine groups, providing favorable chelating properties for metals [101]. This substance was tested for three and a half months in a patient chronically and occupationally exposed to Mn, and authors observed improvement in clinical symptoms such as tremor in hands, handwriting ability, and walking [116]. In fact, another study followed one woman who was exposed for 21 years to airborne Mn and, after treatment with PSA, all clinical symptoms and signs of manganism at the time of treatment were improved, while 17 years after treatment, clinically normal conditions were observed [114].
Preventive treatment with sodium para-aminosalicylic acid inhibits manganese-induced apoptosis and inflammation via the MAPK pathway in rat thalamus
Published in Drug and Chemical Toxicology, 2023
Yue Deng, Dongjie Peng, Chun Yang, Lin Zhao, Junyan Li, Lili Lu, Xiaojuan Zhu, Shaojun Li, Michael Aschner, Yueming Jiang
Sodium para-aminosalicylic acid (PAS-Na) is most commonly used to treat tuberculosis. A follow-up study that lasted for 17 years showed that PAS-Na could also effectively treat Mn-induced occupational Parkinsonism (Jiang et al. 2006). In addition, PAS and its main N acetylated metabolite (AcPAS) can readily cross the blood–brain barrier and reduce free Mn brain levels (Hong et al. 2014). In vitro studies have demonstrated that PAS-Na alleviated Mn-induced cellular damage and apoptosis in neurons (Santos et al. 2013, Wang et al. 2014). Also, in our previous studies, we corroborated that PAS-Na protected the basal ganglia neurons from Mn-induced neurotoxicity (Li et al. 2016), restoring glutamate homeostasis (Li et al. 2020). PAS-Na led to a significant neuroprotective effect by preventing Mn-induced inflammation in BV2 microglial cells (Fang et al. 2021). However, whether PAS-Na affects Mn-induced apoptosis and inflammation in the thalamus has yet to be determined. Hence, this study investigated the effect of Mn on inflammation and apoptotic markers in the rat thalamus, focusing specifically on MAPK pathways.
8-Mercaptoguanine-based inhibitors of Mycobacterium tuberculosis dihydroneopterin aldolase: synthesis, in vitro inhibition and docking studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Alexia de Matos Czeczot, Candida Deves Roth, Rodrigo Gay Ducati, Kenia Pissinate, Raoní Scheibler Rambo, Luís Fernando Saraiva Macedo Timmers, Bruno Lopes Abbadi, Fernanda Souza Macchi, Víctor Zajaczkowski Pestana, Luiz Augusto Basso, Pablo Machado, Cristiano Valim Bizarro
Folate and its derivatives act as cofactors in the biosynthesis of purines, pyrimidines, and amino acids4. Antifolates interrupt the production of folate and its derivatives by inhibiting key enzymes in the folate metabolic pathway5. Among the enzymes of this pathway, only dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) are currently used as targets for antimicrobial agents6. Despite the antimycobacterial activity of antifolates in culture and the use of para-aminosalicylic acid (PAS) as a second-line drug, these molecules are not used in the first-line treatment of TB7,8. The FolB protein, encoded by the folB gene, is a dihydroneopterin aldolase enzyme (DHNA, EC 4.1.2.25), as it converts 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and glycolaldehyde (GA) in the third step of the folate pathway. FolB from Mycobacterium tuberculosis (MtFolB) is also a dihydromonapterin (DHMP) aldolase, converting DHMP to HP and GA, an epimerase, interconverting DHNP and DHMP, and an oxygenase, producing 7,8-dihydroxantopterin (DHXP) from either DHNP or DHMP9. This protein is the first of the three enzymes from the folate pathway that are absent in mammals and represents an attractive target for the development of antimicrobial agents4.
Related Knowledge Centers
- Amine
- Mesalazine
- Salicylic Acid
- 4-Aminosalicylic Acid