Infections by multidrug-resistant Gram-negative Bacteria: What's new in our arsenal and what's in the pipeline?

The spread of multidrug-resistant bacteria is an ever-growing concern, particularly among Gram-negative bacteria because of their intrinsic resistance and how quickly they acquire and spread new resistance mechanisms. Treating infections caused by Gram-negative bacteria is a challenge for medical practitioners and increases patient mortality and cost of care globally. This vulnerability, along with strategies to tackle antimicrobial resistance development, prompts the development of new antibiotic agents and exploration of alternative treatment options. This article summarises the new antibiotics that have recently been approved for Gram-negative bacterial infections, looks down the pipeline at promising agents currently in phase I, II, or III clinical trials, and introduces new alternative avenues that show potential in combating multidrug-resistant Gram-negative bacteria.     

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa

Context: Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive.

Objective: The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms.

Materials and methods: Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism.

Results: In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40?mmHg) at 50?mg/kg with % fall of 27.88?±?4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50?mg/kg with % fall of 45.63?±?2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53?±?4.45% fall in MAP (70?mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K⁺-(80?mM), Ra.Cr induced vasorelaxation and shifted Ca²⁺ concentration–response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca²⁺-free medium.

Discussion and conclusions: The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca²⁺ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.     

Two‐year follow‐up of fractured anterior teeth restored with direct composite resin: report of three cases

Abstract – Thirty‐five (case 1), 15 (case 2) and 22 (case 3)‐year‐old female patients presented to Yeditepe University Dental Faculty Clinic because of esthetic reasons. Fractures of maxillar central incisors including enamel and dentin were diagnosed. Beveling with diamond bur was performed in all four cases. Dentin was cleaned with tungsten carbid bur. The teeth were etched with 37% phosphoric acid, restored with an adhesive system and microhybrid composite. Finishing and polishing procedures were performed by discs (Sof‐Lex) and burs. Restorations were found successful according to modified United States Public Health Service (USPHS) criteria after 2 years in terms of retention, color match, marginal discoloration, secondary caries, marginal adaptation, and surface texture.     

The effect of mineral trioxide aggregate on the contractility of the rat thoracic aorta

Mineral trioxide aggregate (MTA) is being advocated for vital pulp therapy. In the case of direct pulp capping, hemorrhage control is an important step on success, but little is known about the effect of MTA on pulpal bleeding. In addition, there has been a lack of information on the effect of MTA on smooth muscle contraction, such as can occur in the blood vessels of dental pulp. The present study assessed the vascular effects of MTA, using the rat aortic ring preparations as a tissue model. MTA (100-500 mg) induced dose-dependent contraction in rat thoracic aorta. The contractile effect of MTA was blocked by calcium channel blocker nifedipine (1 muM). These data suggest that the vasoconstrictor property of MTA is related to calcium influx and it may allow proper control of hemorrhage which is critical for the success of any pulp-capping treatment.     

Genotype–Phenotype Correlations by Ethnicity and Mutation Location in BRCA Mutation Carriers

The genotype–phenotype correlations of the specific BRCA1 and BRCA2 mutations in multi‐ethnic populations in USA have not yet been fully investigated. This study was designed to evaluate the effects of ethnicity at specific mutation locations and breast/ovarian cancer phenotypes. Our cohort included 445 women with different ethnic backgrounds who underwent BRCA genetic testing between 1997 and 2010. Known clinical and pathologic characteristics were compared with Chi‐Square Analysis or Fisher's Exact test as appropriate. The three most common mutation locations in BRCA1 (exons 2, 11, and 20) and BRCA2 (exons 10, 11, and 25) genes were chosen. Prevalence of BRCA1 exon 2 mutations were significantly higher in Ashkenazi Jewish (AJ) women compared to Caucasians (41% versus 15%; p = 0.001). Similarly, AJ women with breast cancer were more likely to have BRCA1 exon 2 mutation (47% positivity in AJ women versus 0–12.5% positivity in other ethnicities; p = 0.004). Women carrying the exon 20 BRCA1 mutation had the highest probability of having combined breast and ovarian cancers compared to women carrying other exon mutations (p = 0.05). The median age at initial cancer diagnosis, phenotypic features of breast cancer tumors, and overall survival did not vary significantly by ethnicity or mutation location. Our data suggest that ethnicity does not affect age of onset, overall survival or confer different risks of breast and ovarian cancer development in BRCA carriers. These results also suggest that women carrying the exon 20 BRCA1 mutation may warrant mutation‐specific counseling and be more aggressively managed for risk reduction.