Antimicrob Agents Chemother
March 2021
E1224 is a prodrug of ravuconazole (RVZ), an antifungal drug with promising anti- activity, the causative organism of Chagas disease (CD). This study was designed to assess the pharmacokinetics (PK) and safety interactions of benznidazole (BNZ), the drug of choice for treatment of CD, and E1224 in healthy volunteers. This open-label, single-center, sequential, single- and multiple-oral-dose study enrolled 28 healthy male subjects.
View Article and Find Full Text PDFFor more than a century, diabetic patients have been considered immunosuppressed due to defects in phagocytosis and microbial killing. We confirmed that diabetic mice were hypersusceptible to bacteremia caused by Gram-negative bacteria (GNB), dying at inocula nonlethal to nondiabetic mice. Contrary to the pervasive paradigm that diabetes impedes phagocytic function, the bacterial burden was no greater in diabetic mice despite excess mortality.
View Article and Find Full Text PDFThe in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandin-resistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day).
View Article and Find Full Text PDFBackground: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment.
Objective: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs.
Design: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up.
Context: Gulf War veterans' illnesses (GWVI), multisymptom illnesses characterized by persistent pain, fatigue, and cognitive symptoms, have been reported by many Gulf War veterans. There are currently no effective therapies available to treat GWVI.
Objective: To compare the effectiveness of cognitive behavioral therapy (CBT), exercise, and the combination of both for improving physical functioning and reducing the symptoms of GWVI.
The underlying etiology and pathogenesis of Gulf War veterans' illnesses continue to be under intense investigation. Reports have suggested the basis for these illnesses may be an altered immune system, but compelling evidence is lacking. We sought to determine whether in vitro immune responses were abnormal in symptomatic Gulf War veterans relative to matched controls.
View Article and Find Full Text PDFDendritic cells (DC) from blood and other tissues are potent accessory cells for primary immune responses. Because prostaglandins from monocytes and macrophages can suppress DC and T-cell function, we sought to investigate the binding properties of misoprostol (MPL), a prostaglandin E(1) analog, and its regulation of DC function. Results of mouse and human experiments have suggested 1) that MPL could significantly inhibit DC-induced T-cell proliferation in oxidative mitogenesis and allogeneic mixed leukocyte reactions by decreasing interleukin-2 production in DC-T cell cocultures, and 2) that MPL could bind to human peripheral blood mononuclear cells via specific high-affinity MPL binding sites as well as through nonspecific MPL uptake.
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