Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli - an in vitro study

<p>Abstract</p> <p>Background</p> <p>Probiotic bacteria are suggested to play a role in the maintenance of oral health. Such health promoting bacteria are added to different commercial probiotic products. The aim of the study was to investigate the ability of a selection of lactobacilli strains, used in commercially available probiotic products, to inhibit growth of oral mutans streptococci and <it>C. albicans in vitro</it>.</p> <p>Methods</p> <p>Eight probiotic lactobacilli strains were tested for growth inhibition on three reference strains and two clinical isolates of mutans streptococci as well as two reference strains and three clinical isolates of <it>Candida albicans </it>with an agar overlay method.</p> <p>Results</p> <p>At concentrations ranging from 10⁹to 10⁵CFU/ml, all lactobacilli strains inhibited the growth of the mutans streptococci completely with the exception of <it>L. acidophilus </it>La5 that executed only a slight inhibition of some strains at concentrations corresponding to 10⁷and 10⁵CFU/ml. At the lowest cell concentration (10³CFU/ml), only <it>L. plantarum </it>299v and <it>L. plantarum </it>931 displayed a total growth inhibition while a slight inhibition was seen for all five mutans streptococci strains by <it>L. rhamnosus </it>LB21, <it>L. paracasei </it>F19, <it>L. reuteri </it>PTA 5289 and <it>L. reuteri </it>ATCC 55730. All the tested lactobacilli strains reduced candida growth but the effect was generally weaker than for mutans streptococci. The two <it>L. plantarum </it>strains and <it>L. reuteri </it>ATCC 55730 displayed the strongest inhibition on <it>Candida albicans</it>. No significant differences were observed between the reference strains and the clinical isolates.</p> <p>Conclusion</p> <p>The selected probiotic strains showed a significant but somewhat varying ability to inhibit growth of oral mutans streptococci and <it>Candida albicans in vitro</it>.</p

Management of acneiform rash associated with anti-EGFR monoclonal antibody treatment

Introduction. Dermatologic adverse events (DAEs) occur in 50-90% of cases during anti-EGFR monoclonal antibody treatment. Positive correlation between the severity of acneiform rash (AR) and the effectiveness of anti-EGFR management is established. Low effectiveness of traditional treatment for AR impairs patients’ compliance, leads to dose reduction or drug discontinuation, affecting treatment results.Objective. To assess the effectiveness of traditional and proposed combined treatment for AR associated with anti-EGFR monoclonal antibody therapy.Materials and methods. 44 patients with grade I-II acneiform rash were included in a 12-week study. Patients were divided into 3 equal groups and received different treatment: group 1a – traditional therapy, group 1b – combined continuous therapy, and group 1c – combined intermittent therapy. Assessment of clinical outcomes was performed with DLQI, IGA score, and the NCI CTCAE v. 4.03.Results. The severity of AR in groups 1b and 1c improved by the end of week 1, and this trend was kept until the end of the study. The improvement was more prominent in group 1c comparing to group 1b. The severity of AR in group 1a improved by the end of week 1. During weeks 2 and 3 there was no significant change. At week 4 a deterioration of the evaluated parameters was registered, and the treatment regimen in group 1a was changed according to the treatment protocols of group 1c with rapid improvement of AR.Conclusion. Combined intermittent therapy with systemic doxycycline and topical therapy with metronidazole 1% gel and cream with hydrocortisone acetate 1% and fusidic acid 2% showed the best effectiveness and tolerability in patients with anti-EGFR monoclonal antibody-related AR

Loss Of COP9-signalosome genes Aa 2q37 is associated with IMiD agent resistance in multiple myeloma

The acquisition of a multi-drug refractory state is a major cause of mortality in myeloma. Myeloma drugs that target the Cereblon (CRBN) protein include widely-used immunomodulatory drugs (IMiDs), and newer CRBN E3 ligase modulator drugs (CELMoDs), in clinical trials. CRBN genetic disruption causes resistance and poor outcomes with IMiDs. Here we investigate alternative genomic associations of IMiD resistance, using large whole genome sequencing patient datasets (n=522 cases) at newly diagnosed, lenalidomide (LEN)-refractory and lenalidomide-then-pomalidomide (LEN-then-POM)-refractory timepoints. Selecting gene targets reproducibly identified by published CRISPR/shRNA IMiD resistance screens, we found little evidence of genetic disruption by mutation associated with IMiD resistance. However, we identified a chromosome region, 2q37, containing COP9-signalosome members COPS7b and COPS8, copy loss of which significantly enriches between newly-diagnosed (incidence 5.5%), LEN-refractory (10.0%) and LEN-then-POM-refractory states (16.4%), and may adversely affect outcomes when clonal fraction is high. In a separate dataset (50 patients) with sequential samples taken throughout treatment, we identified acquisition of 2q37 loss in 16% cases with IMiD exposure, but none in cases without IMiD exposure. The COP9 signalosome is essential for maintenance of the CUL4-DDB1-CRBN E3 Ubiquitin Ligase. This region may represent a novel marker of IMiD resistance with clinical utility