We conducted a randomized, double-blind, placebo-controlled trial to compare a 3-day quinine-clindamycin regimen (group QC) with a 7-day quinine regimen (group Q) for the treatment of uncomplicated Plasmodium falciparum malaria in travelers returning from the tropics. A total of 55 and 53 patients in groups Q and QC were analyzed, respectively. Adverse effects were similar in both groups, although two patients in group Q had severe adverse reactions, leading to the cessation of treatment. The 28-day cure rate for the evaluated patients (per-protocol analysis) was 100% for group QC, whereas it was 96.3% for group Q (P ؍ 0.5). The 28-day cure rate in the intention-to-treat analysis was 96.2% for group QC, whereas it was 94.6% for group Q (P ؍ 1). There were no significant differences between the two regimens with regard to parasite and fever clearance times. Our study shows that the 3-day quinine-clindamycin regimen is well tolerated and compares favorably with a 7-day quinine treatment. This short-term regimen had previously been evaluated only in areas of endemicity. According to our results, the 3-day quinine-clindamycin regimen may be an alternative for the treatment of imported uncomplicated P. falciparum malaria in travelers returning from the tropics.
Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.
A novel set of N-alkyl naphthyridone compounds has been prepared and characterized.These compounds have been compared to analogous 9-acridinones for a possible trypanocidal activity. With reference to this, naphthyridones seem to be more promising compounds than the 9-acridinone ones. INTRODUCTIONWithin the scope of the search of new trypanocidal agents (1-3) we have recently prepared and tested some 1,4-dimethoxy-9-(10H)-acridinone derivatives (4). As the naphtyridine nucleus is structurally related to the acridine one, we were also interested in preparing and investigating antiparasitic activity of some new benzo [b][1,8]-5-naphthyridone derivatives, substituted similarly as acridinones already tested. EXPERIMENTAL Synthesis, trypanocidal activity and DNA binding of new benzo [b] [ 1,8]-naphthyridones derivatives -ChemistryMelting points were determined in open capillary tubes on a Buchi-Tottoli apparatus and are given uncorrected. NMR spectra were recorded at 20.00 ± 0.1 °C, using a Bruker AM 200 spectrometer. Microanalyses were carried out using a Technicon CHN autoanalyzer.G6n6ral procedure for synthesis of compounds 1-8 (scheme 1) Procedure for compounds land 2.A mixture of freshly distilled aniline or properly substituted anilines (80 mmol), 2-chloro nicotonic acid (80 mmol), copper (0.8 g) and xylene (200 ml) is refluxed for 24 h with stirring.After filtration, the mixture is allowed to cool to room temperature. The precipitate obtained is recrystallized. Procedure for compounds 2_and_4Anthranilic acids 1 or 2 (10 mmol) are refluxed for 4 h with polyphosphoric acid in excess (more than 20 fold the weight of anthranilic acid). Then, the mixture is poured on ice and ammonia is slowly added. The precipitate obtained is recrystallized. Procedure for compounds 5 and_£A mixture of naphthyridone 2 or 4 (10 mmol), alkylating agent (15 mmol), and triethylbenzylammonium chloride hydrochloride (5 mmol), aqueous 50 % potassium hydroxide (50 ml), and toluene (100 ml) is refluxed for 24 h with stirring. Then, the organic layer is separated, washed with water, and dried with anhydrous sodium sulfate. After evaporation of solvent, crude product is recrystallized.Procedure for compound Ζ A mixture of £ (2 mmol) and 40 % hydrobromic acid (320 mmol), is refluxed for 4 h with stirring before being allowed to cool to room temperature. Solution is then neutralized with ammonia, with cooling to maintain the temperature at 0° C. The precipitate obtained is recrystallized.
Objective: To evaluate the impact of protease inhibitors on drug cost and frequency of admission-defining events for HIV-infected patients in the infectious diseases unit of F Houphouët Boigny Hospital in Marseilles, France, which provides conventional hospitalization and outpatient care.Methods: Data from a prospective eight-year study conducted from January 1,1990, to December 31,1997, were used. Data from nurse records were collected daily by a pharmacy resident. Statistical analyses were performed to compare 1997 data with previous years, since protease inhibitors were not available in France until March 1996.Results: A total of 1,558 inpatients, accounting for 2,717 admissions, participated in the study. From 1995 to 1997, we observed a decrease in the percentage of hospitalized patients compared with the total number of patients (48.8%). We also noticed a reduction in number of stays (52%) and mean duration of stays (from 16.06 ± 1.81 to 11.08 ± 1.80 d). Total drug cost in the inpatient care unit dropped by one-half (based on 100 patients/y). The number of hospital admissions and mean drug cost per stay also decreased for some opportunistic infections described as late complications of AIDS; at the same time, drug costs in the outpatient unit rose sharply. Conclusions:This study confirms recent advances in HIV management. Use of protease inhibitors has reduced the relative risk of opportunistic infections and cost of inpatient treatment. This reduction has been associated with a sharp cost increase for outpatient therapy, resulting from widespread use of protease inhibitors.
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