Browsing by Subject "Amines"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Open Access Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.(Translational psychiatry, 2021-03-02) MahmoudianDehkordi, Siamak; Ahmed, Ahmed T; Bhattacharyya, Sudeepa; Han, Xianlin; Baillie, Rebecca A; Arnold, Matthias; Skime, Michelle K; John-Williams, Lisa St; Moseley, M Arthur; Thompson, J Will; Louie, Gregory; Riva-Posse, Patricio; Craighead, W Edward; McDonald, William; Krishnan, Ranga; Rush, A John; Frye, Mark A; Dunlop, Boadie W; Weinshilboum, Richard M; Kaddurah-Daouk, Rima; Mood Disorders Precision Medicine Consortium (MDPMC)Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines-including arginine, proline, and methionine sulfoxide-were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics-including acylcarnitine metabolism, transport, and its link to β-oxidation-and lipid membrane remodeling may play roles in SSRI treatment response.Item Open Access Chronic Lyme disease: the controversies and the science.(Expert Rev Anti Infect Ther, 2011-07) Lantos, Paul MThe diagnosis of chronic Lyme disease has been embroiled in controversy for many years. This is exacerbated by the lack of a clinical or microbiologic definition, and the commonality of chronic symptoms in the general population. An accumulating body of evidence suggests that Lyme disease is the appropriate diagnosis for only a minority of patients in whom it is suspected. In prospective studies of Lyme disease, very few patients go on to have a chronic syndrome dominated by subjective complaints. There is no systematic evidence that Borrelia burgdorferi, the etiology of Lyme disease, can be identified in patients with chronic symptoms following treated Lyme disease. Multiple prospective trials have revealed that prolonged courses of antibiotics neither prevent nor alleviate such post-Lyme syndromes. Extended courses of intravenous antibiotics have resulted in severe adverse events, which in light of their lack of efficacy, make them contraindicated.Item Open Access Platinum(II)-catalyzed intermolecular hydroamination of monosubstituted allenes with secondary alkylamines.(Chem Commun (Camb), 2010-03-14) Toups, Kristina L; Widenhoefer, Ross AA 1:1 mixture of (dppf)PtCl(2) and AgOTf (5 mol%) catalyzed the intermolecular hydroamination of monosubstituted allenes with secondary alkylamines at 80 degrees C to form allylic amines in good yield with selective formation of the E-diastereomer.