First report of blaOXA-24 carbapenemase gene, armA methyltransferase and aac(6')-Ib-cr among multidrug-resistant clinical isolates of Proteus mirabilis in Algeria.

OBJECTIVE: Carbapenemase-producing, or carbapenem-resistant, Enterobacteriaceae are an emerging threat to human and animal health because they are resistant to many of the last-line antimicrobials available for treatment of infection. The aim of this study was to analyse the antimicrobial resistance patterns and their encoding genes of Proteus mirabilis isolated in Constantine, Algeria. METHODS: A total of 108 Proteus, Morganella and Providencia (PMP) strains were isolated from a large variety of clinical specimens at University Hospital of Constantine in Algeria. Isolates were identified using the API 20E system and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Diagnostic accuracy was determined by independent comparison of each method to phylogenetic analysis based on 16S rRNA gene sequencing. Antimicrobial susceptibility was determined by the standard disk diffusion and Etest methods. The presence of antimicrobial resistance genes was screened for by PCR amplification and sequencing. RESULTS: A total of 72 PMP strains were multidrug-resistant (MDR). Among them, one P. mirabilis isolate was resistant to imipenem with a minimum inhibitory concentration (MIC) of ≥12µg/mL. PCR and sequencing showed the presence of various antimicrobial resistance genes, including blaCTX-M-15, blaTEM-1, blaTEM-2, blaPER-1, blaSHV-11, aadA1, aadA2, armA, aac(6')-Ib, aac(6')-Ib-cr, aac(3)-Ia and ant(2″)-I, forming different resistance profiles. Moreover, the blaOXA-24 gene was detected in the imipenem-resistant P. mirabilis strain. CONCLUSION: In this study, a MDR P. mirabilis isolate harbouring the blaOXA-24, armA 16S rRNA methylase and aac(6)-Ib-cr genes was found for the first time in Algeria.

Antidiabetic, antioxidant and anti inflammatory properties of water and n-butanol soluble extracts from Saharian Anvillea radiata in high-fat-diet fed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties. MATERIALS AND METHODS: Six extracts (water soluble and organic) from aerial parts of the plant were analyzed phytochemically (total phenolic and flavonoid content) and screened for in vitro superoxide (by chemiluminescence) and hydroxyl radical (by electron paramagnetic resonance spin-trapping) scavenging, antioxidant (DPPH, TRAP and ORAC assays), xanthine oxidase, metal chelating, α-amylase and α-glucosidase inhibitory property, and protective effects on copper-induced lipoprotein oxidation. Then selected hydroalcoholic and aqueous extracts were assessed for toxicity in normal human lung fibroblasts and A549 cancer cells using FMCA and MTT assays. Two water-soluble extracts having the best overall properties were assessed for their (i) protective effect at 1-15µg/mL on metabolic activity of rat insulinoma-derived INS-1 cells exposed to hyperglycemic medium, and (ii) acute hypoglycemic effect on 16-weeks HFD-induced diabetic mice. Then diabetic mice were administered HFD supplemented by extracts (up to 150mg/kg/day) for 12 additional weeks using standard diet as control and the antidiabetic drug, metformin (150mg/kg), as positive control. Then the antidiabetic, anti-inflammatory and antioxidant activity of extracts were determined. RESULTS: Of the highly efficient polyphenolics-enriched hydroalcoholic and ethyl acetate extracts, the lyophilized aqueous (AQL) and butanol extracts were not toxic in cells (≤ 400µg/mL) or when given orally in normal mice (≤ 2000mg/kg), exerted a dose-dependent hypoglycemic action in diabetic mice, which was maximal at the dose of 150mg/kg. Upon administering this dose for 12 weeks, both extracts significantly ameliorated body weight control capacity, recovery of plasma glucose and insulin level, reduced oxidative stress in blood, myocardial and skeletal muscles, and improved hyperlipidemic and inflammatory status. Moreover, diabetes-related complications were optimally ameliorated by oral therapy based on halved doses (75mg/kg) of a mixture of AQL and metformin. CONCLUSIONS: Current investigation supports the traditional medicinal usage of Anvillea radiata and suggests that both readily accessible and low-cost bio-extracts have the potency to develop an antihyperglycemic, antihyperlipidemic and protective agent against beta-cells and muscle dysfunction at doses compatible with the common practices of indigenous people for the management of metabolic disorders.

On the vasoprotective mechanisms underlying novel ß-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress.

A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential on eleven different radicals and NO-donation properties in vitro, cytotoxicity and vasoprotective effect on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl- and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, and 4g-4i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.