Non-Antimicrobial Drugs: Etodolac as a Possible Antimicrobial or Adjuvant Agent Against ESKAPE Pathogens.

INTRODUCTION: Multiple-drug resistant bacteria are emerging exponentially in healthcare units, threatening public health and requiring novel therapeutic approaches. In 2017, World Health Organization published a list that frames antimicrobial resistant bacteria into priority levels for research of novel drugs to fight them. METHODS & MATERIALS: Antimicrobial resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter sp.) and Enterococcus faecalis and Escherichia coli pathogens are present in this list. Representative isolates of each species were used to test the Antibacterial and anti-biofilm formation activities of Etodolac (a Non-Steroidal Anti-Inflammatory Drug, NSAID) at 10 and 1 mM using a broth microdilution technique. RESULTS & DISCUSSION: Statistically significant (p< 0,05) results were observed against all tested gram-positives, particularly anti-biofilm activity against E. faecium. Etodolac had an almost null influence on tested gram-negatives, with the exception of one A. baumannii clinical isolate regarding biofilm formation inhibition. Observed differences deserve further analysis and prospection of the involved mechanisms, to unravel possible novel bacterial targets for drug development. Similar work with other NSAID's may also be worth exploring to ascertain novel therapeutic applications for these drugs, particularly regarding biofilm formation inhibition, per si or as adjuvants of current antibiotherapy, mainly against gram-positives, as suggested by present work. CONCLUSION: Already approved drugs in terms of pharmacokinetics and safety may deploy faster solutions for antimicrobial therapy against priority pathogens. Current work intends to bring attention to that possibility, particularly regarding NSAIDs, anti-biofilm formation and top priority pathogens.

Microbiota of Chronic Diabetic Wounds: Ecology, Impact, and Potential for Innovative Treatment Strategies.

World Health Organization considered diabetes as one of the 20th century epidemics, estimating that over 10% of the world population is diabetic or at high risk. Self-assessment studies indicate that diabetic patients consider chronic wounds to affect their quality of life more dramatically than vision loss or renal failure. In addition to being the main reason for diabetic patients' hospitalization, the economic burden of diabetic chronic wounds is close to 1% of United Kingdom and United States health systems budgets, which exceeds the funds allocated to the treatment of some types of cancer in both countries. Among the factors preceding the emergence of chronic diabetic wounds, also designated diabetic foot ulcers (DFUs), hygiene and pressure in specific areas are under patient control, while others are still far from being understood. A triple impairment in the innervation, immune responses, and vascularization associated to DFU has been extensively studied by the scientific community. However, the skin natural microbiota has only recently emerged as having a tremendous impact on DFU emergence and evolution to chronicity. Despite the great inter- and intra-variability of microbial colonizers, ongoing efforts are now focused on deciphering the impact of commensal and pathogenic microbiota on DFU etiology, as well as the mechanisms of interkingdom microbial-host communication. This review summarizes recent work in this context and offers new microbiological perspectives that may hold potential in the prevention and treatment of chronic diabetic wounds.

Pullulanibacillus uraniitolerans sp. nov., an acidophilic, U(VI)-resistant species isolated from an acid uranium mill tailing effluent and emended description of the genus Pullulanibacillus.

Two Gram-positive-staining, rod-shaped, endospore-forming isolates (UG-2(T) and UG-3), with an optimum growth temperature of around 37 °C and an optimum pH for growth of about 4, were recovered from an acidic effluent of the uranium mill tailing at Urgeiriça in Central Portugal. On the basis of 16S rRNA gene sequence similarity, the strains belonged to the family Sporolactobacillaceae and were closely related to Pullulanibacillus naganoensis ATCC 53909(T) (97.9 %). Unlike P. naganoensis, strains UG-2(T) and UG-3 grew in medium containing up to 5000 p.p.m. U(VI) but did not hydrolyse pullulan. Chemotaxonomic data also supported the affiliation of strains UG-2(T) and UG-3 to the genus Pullulanibacillus. Physiological and biochemical tests along with fatty acid composition allowed differentiation of strains UG-2(T) and UG-3 from P. naganoensis. It is suggested that strains UG-2(T) and UG-3 represent a novel species, for which the name Pullulanibacillus uraniitolerans is proposed; the type strain is UG-2(T) (=DSM 19429(T) = LMG 24205(T)). An emended description of the genus Pullulanibacillus is also proposed.

Effect of curing protocol on the polymerization of dual-cured resin cements.

OBJECTIVES: The purpose of this study was to evaluate how curing protocol affects the extent of polymerization of dual-cured resin cements. METHODS: Four commercial resin cements were used (DuoLink, Panavia F 2.0, Variolink II and Enforce). The extent of polymerization of the resin cements cured under different conditions was measured using a (1)H Stray-Field MRI method, which also enabled to probe molecular mobility in the kHz frequency range. RESULTS: Resin cements show well distinct behaviours concerning chemical cure. Immediate photo-activation appears to be the best choice for higher filler loaded resin cements (Panavia F 2.0 and Variolink). A photo-activation delay (5 min) did not induce any significant difference in the extent of polymerization of all cements. SIGNIFICANCE: The extent of polymerization of dual-cured resin cements considerably changed among products under various curing protocols. Clinicians should optimize the materials choice taking into account the curing characteristics of the cements.

Novel light-cured resins and composites with improved physicochemical properties.

OBJECTIVES: The aim of this study was to determine the effect of two new diluent agents (Bis-GMA analogues), at different dilution levels and filler contents on relevant physicochemical properties of several novel resins and composites containing Bis-GMA as matrix. Composites using TEGDMA as diluent were used as control. METHODS: Twenty formulations were prepared combining three monomer mixtures (Bis-GMA/TEGDMA, Bis-GMA/CH(3) Bis-GMA and Bis-GMA/CF(3) Bis-GMA), at three dilution levels (85/15, 10/90, 0/100) and two percentages of filler loading (silanated barium aluminosilicate glass): 0%, 10%, 35%. Preliminary rheological testing was performed in order to obtain the viscosity of the resin samples. Resins and composites were then inserted into molds and light-cured (500mW/cm(2)). The properties evaluated were: (1) homogeneity of curing (HC), using FTIR or Vickers microindentor, (2) microhardness, by a Vickers microindentor, (3) depths of cure and oxygen inhibitor effect (OIE), quantified by scraping, (4) water contact angle on the materials surface, (5) water sorption and solubility, performed by the Oysaed-Ruyter method and (6) scanning electron microscopy analysis of the specimens surfaces. Data were analyzed by ANOVA and Student-Newman-Keuls tests (p<0.05). RESULTS: Materials with CH(3) Bis-GMA and CF(3) Bis-GMA exhibited less hydrophilicity, water sorption and solubility. Bis-GMA dilution induced an increase in depth of cure and promoted a higher OIE, particularly when the diluent was TEGDMA. Filler loading reduced the OIE and increased hydrophobicity of the resins. SIGNIFICANCE: CH(3) Bis-GMA may be considered as good candidate to be used as diluent because when replacing TEGDMA-induced lower hydrolytic degradation and increase in HC.

Evaluation of two Bis-GMA analogues as potential monomer diluents to improve the mechanical properties of light-cured composite resins.

OBJECTIVES: The aim of this study was to investigate the influence of new diluent agents, diluent ratio and filler content, on relevant mechanical properties of several novel composite resins containing Bis-GMA as resin matrices, and to compare these with the properties of composites based on TEGDMA, a conventionally used diluent. METHODS: Two Bis-GMA analogues were synthesized and 20 experimental composite resins were prepared combining three monomer mixtures (Bis-GMA/TEGDMA, Bis-GMA/CH3 Bis-GMA and Bis-GMA/CF3 Bis-GMA), at three dilution rates (85/15, 10/90, 0/100) and three levels of hybrid filler content (barium aluminosilicate glass): 0, 10 and 35%. Flexural strength (FS), modulus of elasticity (ME) and microhardness (VHN) of the composites were evaluated. Five specimens of each material were prepared for each mechanical test, light-cured over 120 s and stored in water at 37 degrees C for 1 week. Three-point bending test was used for FS measurement and VHN was quantified by using a Vickers microindentor. Data were analyzed by ANOVA and Student-Newman-Keuls tests (P<0.05). RESULTS: Materials with CH3 Bis-GMA showed an enhanced VHN. Mean FS was higher for matrices containing TEGDMA. Overall, dilution favored FS and VHN but not ME. Filler loading specially improved ME and VHN. SIGNIFICANCE: Results correlate with an increase in the extent of polymerization due to the higher flexibility of the less viscous comonomer starting system and the hydrophobic character of the Bis-GMA analogues.