ABSTRACT
INTRODUCTION: Rickettsioses are diseases caused by intracellular Gram-negative bacteria of the Rickettsiaceae family and transmitted through the bite of infected ticks or mites. AIM OF STUDY: To investigate the clinical and subclinical characteristics and prognostic severe factors of the disease caused by Rickettsiaceae. METHODS: A prospective, descriptive cross-sectional study was conducted at Department of Infectious Diseases of two military hospitals in Northern Vietnam from May 2013 to June 2019, in which 88 adult febrile patients caused by Orientia tsutsugamushi (50 patients) or Rickettsia spp. (38 patients) were enrolled. We recorded information regarding epidemiological characteristics (age, geography, residence, occupation), medical history, clinical and subclinical findings, life-threatening complications during treatment, outcomes and some factors predicting serious life-threatening complications in a case record form. RESULTS: Scrub typhus (ST) patients had eschar (70%), skin-conjunctiva congestion (60%) and lymphadenopathy (44%). Rickettsia patients had a higher rate of maculopapular rash (39.5%), no ulcers and no lymphadenopathy detected. The majority of patients had elevated PCT >0.05 ng/µL and increase in liver enzymes and thrombocytopenia. Major prognostic factors for severe complications included diffuse infiltrates on lung X-ray (OR: 19.5; p = 0.014), coarse crackles (OR: 18; p = 0.016), respiratory rate ≥25 cycles/minute (OR: 18; p = 0.016), shortness of breath (OR: 7.44; p = 0.003), pleural fluid (OR: 4.3; p = 0.035) and increase in AST ≥ 200 UI/l (OR: 4.42; p = 0.012). The PCT value is able to distinguish between the two groups with quite high reliability (the area under the ROC curve is 0.75). CONCLUSION: Eschar and peripheral lymphadenopathy were two valuable clinical symptoms for the diagnosis of scrub typhus and distinguishing 2 groups of diseases. Respiratory distress, increase in AST ≥ 200 UI/l and level of PCT were used as major prognostic factors in patients with Rickettsiaceae.
ABSTRACT
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible prostaglandin E synthase that catalyzes the conversion of prostaglandin PGH(2) to PGE(2) and represents a novel target for therapeutic treatment of inflammatory disorders. It is essential to identify mPGES-1 inhibitor with novel scaffold as new hit or lead compound for the purpose of the next-generation anti-inflammatory drugs. Herein we report the discovery of sulfonamido-1,2,3-triazole-4,5-dicarboxylic derivatives as a novel class of mPGES-1 inhibitors identified through fragment-based virtual screening and in vitro assays on the inhibitory activity of the actual compounds. 1-[2-(N-Phenylbenzenesulfonamido)ethyl]-1H-1,2,3-triazole-4,5-dicarboxylic acid (6f) inhibits human mPGES-1 (IC(50) of 1.1 µM) with high selectivity (ca.1000-fold) over both COX-1 and COX-2 in a cell-free assay. In addition, the activity of compound 6f was again tested at 10 µM concentration in presence of 0.1% Triton X-100 and found to be reduced to 1/4 of its original activity without this detergent. Compared to the complete loss of activity of nuisance inhibitor with the detergent, therefore, compound 6f would be regarded as a partial nuisance inhibitor of mPGES-1 with a novel scaffold for the optimal design of more potent mPGES-1 inhibitors.
