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Genetic Disorders of the Autonomic Nervous System
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Shortly after DBH was recognized as an important step in catecholamine synthesis, attempts were made to treat hypertension with DBH inhibitors. Disulfiram (Antabuse), a copper chelator, was early recognized to inhibit DBH (Hoeldtke et al., 1988). Early clinical studies also demonstrated that fusaric acid and its precursor bupicomide could lower blood pressure in hypertensive subjects and decrease serum DBH activity (Nagatsu, 1986). However, tachycardia and increased excretion of urinary catecholamines were observed. This apparent contradiction can be explained by the fact that fusaric acid apparently stimulates the release of catecholamines from the adrenal gland. More specific and potent DBH inhibitors are currently being tested as antihypertensive agents. As in our patients, inhibition of DBH following the administration of SKF 102698 to rats results in a decrease in plasma and tissue noradrenaline associated with an increase in dopamine levels (Ohlsteineí etal., 1987). Also, as our results withmetyrosine suggest, the hypotensive effects of specific DBH inhibitors may be related to both a decrease in noradrenaline and an increase in dopamine with its attendant vasodilatory and natriuretic effects.
Lipids and Lipid-Like Compounds of Fusarium
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
A. H. Merrill, A. M. Grant, E. Wang, C. W. Bacon
Fusarin C is toxic and mutagenic and represents just one of the many secondary metabolites of Fusarium (T-2 toxin, fusaric acid, moniliformin, nivalenol, deoxynivalenol, beauvericin and diacetoxy-scirpenol) and will be discussed in depth because they are important contributors to some of the diseases caused by F. monoliforme.
Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid
Published in Drug and Chemical Toxicology, 2020
Sevcan Mamur, Fatma Ünal, Serkan Yılmaz, Esra Erikel, Deniz Yüzbaşıoğlu
Fusarium fungi are commonly found in temperate climates and their toxins are possibly the most economically significant grain mycotoxins on the global basis (Wood 1992). They produce trichothecenes, such as HT-2 toxin, T-2 toxin, deoxynivalenol, diacetoxyscirpenol, monoacetoxy-scirpenol, zearalenone, moniliformin, fumonisins, verrucarin A, and fusaric acid (FA) (De Nıjs et al. 1996, Mezes 2008). FA (5-butylpicolinic acid) is a phytotoxin (Gaumann 1957, Stankovic et al.2007) produced by various Fusarium species especially Fusarium moniliforme which grow on maize (Voss et al.1999, Abdul et al.2016). It was first discovered during the laboratory culture of Fusarium heterosporum nees by Yabuta et al. (1937) (Bacon et al.1996). FA was reported to be a potent inhibitor of dopamine b-hydroxylase, which is an indicator for nervous system activity (Reddy et al.1996) and it may interact synergistically with other natural toxins (Bacon et al.1995, 1996, Porter et al.1995, 1996, Voss et al.1999).
Dopamine β hydroxylase as a potential drug target to combat hypertension
Published in Expert Opinion on Investigational Drugs, 2020
Sanjay Kumar Dey, Manisha Saini, Pankaj Prabhakar, Suman Kundu
In spite of a large number of inhibitors identified against DBH, BP in humans was reduced by only a few compounds. For example, only fusaric acid made it to the clinical trial in humans out of many copper chelators [53]. Results of this clinical study showed that daily doses of 150 or 600 mg of fusaric acid produced an uniform antihypertensive effect on either of hypertensive (lowered BP by 20 mm Hg) or normotensive patients (lowered BP by 10 mm Hg) [105]. For the superior mesenteric, renal, and femoral circulations which were perfused with blood, a close-arterial injection of fusaric acid (10–30 mg) increased in the rates of flow in a dose-dependent manner [105].
Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge
Published in Expert Review of Anti-infective Therapy, 2020
Teresa Gil-Gil, José Luis Martínez, Paula Blanco
Not only RND efflux pumps are known to be involved in S. maltophilia phenotypic resistance. Another ABC-like tripartite efflux system, named FuaABC, which is involved in fusaric acid resistance has been also identified in the genome of S. maltophilia K279a. The operon is induced in the presence of fusaric acid and, when overexpressed, contributes to S. maltophilia resistance against this compound [118].