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Clinical features of malaria
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
Acute psychiatric symptoms, as both the presenting feature and sequel to an attack of malaria, have been frequently reported, especially in the older literature (Anderson, 1927). However, in many cases, there were failures to confirm the diagnosis of malaria, to exclude a role for antimalarial and other drugs and to take into account the patient’s previous personality. Mepacrine (quinacrine, atabrine), which was widely used for the prevention and treatment of malaria in the 1930s and 1940s, chloroquine, which was introduced in the 1950s, and mefloquine have been reported to cause psychiatric symptoms. Alcohol excess, stresses associated with life or military service in tropical countries and exacerbation of pre-existing functional psychoses may also have been implicated in ‘malarial psychosis’. Organic mental disturbances associated with malaria have been identified in some cases, usually during convalescence after the fever has subsided. Features have included apathy, amnesia, depression, atypical depression, acute psychosis, personality change, paranoid psychosis and delusions, such as the belief that family members had been killed. Brief reactive psychoses have been observed in patients recovering from cerebral malaria. These symptoms rarely persist for more than a few days, unlike those caused by functional psychoses.
Iodoquinol and Quinacrine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Quinacrine, also known as mepacrine hydrochloride, was synthesized by scientists at Bayer in Germany in 1931. It was one of the first synthetic antimalarial substitutes for quinine but was later superseded by chloroquine because of the latter’s more favorable toxicity profile. During World War II, it was marketed as Mepacrine or Atabrine, and it has been used for malaria chemoprophylaxis. More recently, it has been used as an antiprotozoal agent because it has activity against G. lamblia as well as Plasmodium species. However, quinacrine is now rarely used to treat giardiasis because of the drug’s toxicity and the superiority of metronidazole for this indication (see Chapter 99, Metronidazole) (Upcroft and Upcroft, 2001). Quinacrine has also been used for the treatment of tapeworm, but it has been replaced for this indication by newer, less toxic agents. It is an acridine derivative that is both water and alcohol soluble, with the chemical formula C23H30ClN3O and a molecular weight of 400.0 g/mol; the chemical structure is shown in Figure 191.2.
Antimalarials
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Ocular adverse effects, specifically an irreversible retinopathy with blindness, are the major risk associated with chloroquine and hydroxychloroquine treatment. The maculopathy may progress even after the cessation of the drug. Low dose hydroxychloroquine carries a very small risk of this complication, while mepacrine has negligible ocular toxicity.
Diagnosis of platelet function disorders: A standardized, rational, and modular flow cytometric approach
Published in Platelets, 2018
Oliver Andres, Katja Henning, Gabriele Strauß, Annerose Pflug, Georgi Manukjan, Harald Schulze
Since platelets of patients with AML under induction therapy exhibit a known hyporeactivity [18], we investigated a cohort of 15 adult patients in this treatment phase. Even though these patients showed broad variation in platelet size (FSC) and granularity (SSC), platelets seemed to be overall faintly smaller and less granulated (Figure 4A). Expression of the platelet fibrinogen, laminin and fibronectin receptors was markedly decreased in most patients. The GPIb-IX-V complex was less affected and showed normal expression levels in the majority of patients (Figure 4A). However, in comparison to healthy individuals, platelets of these patients were generally hyporeactive as neither ADP nor TRAP6 were capable to induce adequate neo-exposition of CD62P and CD63 nor activated CD41/CD61 as shown by reduced PAC-1 antibody binding (Figure 4B). In five patients, suboptimal doses of TRAP6 did not result in any PAC-1 binding. As platelet calcium mobilization was normal in all four tested individuals, hyporeactivity could not be attributed to early signaling pathways (Figure 4C left). Mepacrine loading was significantly decreased in each of the three investigated patients, whereas mepacrine release appeared intact (Figure 4C right).
TGFβ as a therapeutic target in cystic fibrosis
Published in Expert Opinion on Therapeutic Targets, 2018
Elizabeth L. Kramer, John P. Clancy
Several approved medications have known effects on TGFβ signaling pathways, although the exact mechanism of these effects is often not well understood. Pirfenidone, currently approved for IPF, blocks TGFβ signaling and production by an unclear mechanism; TGFβ1-induced airway surface liquid (ASL) dehydration in CF bronchial epithelial cells has been shown to be abrogated by treatment with pirfenidone in vitro [74,138]. Losartan, an angiotensin II type 1 receptor inhibitor, reduces TGFβ signaling and also reduces mucociliary dysfunction in CF bronchial epithelial cells after TGFβ treatment [139]. Corticosteroids have been demonstrated to inhibit TGFβ1 expression in a mouse model of asthma, yet these results have not been replicated in humans, and the utility of using corticosteroids to reduce TGFβ signaling is unclear [88]. Simvastatin, used primarily for its lipid-lowering effects, also inhibits TGFβ1-induced myofibroblast production [140]. Finally, mepacrine, an anti-malarial drug, inhibits TGFβ1 expression and subepithelial fibrosis in a mouse model of asthma [141]. As these medications have known side-effect profiles and are approved for other indications in humans, they represent low-hanging fruit in the search for TGFβ modifying medications in CF. However, their utility and direct translation to CF may be limited by off target effects and unclear mechanisms of action.
Flow cytometry for pediatric platelets
Published in Platelets, 2019
Anastasia A. Ignatova, Evgeniya A. Ponomarenko, Dmitry M. Polokhov, Elena V. Suntsova, Pavel A. Zharkov, Daria V. Fedorova, Ekaterina N. Balashova, Anastasia E. Rudneva, Vadim V. Ptushkin, Evgeniy A. Nikitin, Anna Shcherbina, Alexei A. Maschan, Galina A. Novichkova, Mikhail A. Panteleev
Dense granule function was evaluated based on mepacrine fluorescence both in the resting platelets (100 ± 12 units) and that remaining in the stimulated ones (24 ± 12 units). Under conditions of the assay, therefore, more than three thirds of mepacrine was released. Two derived parameters, mepacrine release determined as their difference (76 ± 12 units) and activation index determined as their ratio (4.4 ± 0.8) were used to evaluate absolute and relative secretion efficiency, respectively. The quantity of mepacrine determined in the resting pediatric platelets was significantly decreased compared with adults (about 75%).