Biopolymer Nano-Network for Antimicrobial Peptide Protection and Local Delivery

Antimicrobial resistance (AMR) develops when bacteria no longer respond to conventional antimicrobial treatment. The limited treatment options for resistant infections result in a significantly increased medical burden. Antimicrobial peptides offer advantages for treatment of resistant infections, including broad-spectrum activity and lower risk of resistance development. However, sensitivity to proteolytic cleavage often limits their clinical application. Here, a moldable and biodegradable colloidal nano-network is presented that protects bioactive peptides from enzymatic degradation and delivers them locally. An antimicrobial peptide, PA-13, is encapsulated electrostatically into positively and negatively charged nanoparticles made of chitosan and dextran sulfate without requiring chemical modification. Mixing and concentration of oppositely charged particles form a nano-network with the rheological properties of a cream or injectable hydrogel. After exposure to proteolytic enzymes, the formed nano-network loaded with PA-13 eliminates Pseudomonas aeruginosa during in vitro culture and in an ex vivo porcine skin model while the unencapsulated PA-13 shows no antibacterial effect. This demonstrates the ability of the nano-network to protect the antimicrobial peptide in an enzyme-challenged environment, such as a wound bed. Overall, the nano-network presents a useful platform for antimicrobial peptide protection and delivery without impacting peptide bioactivity.ISSN:2192-2640ISSN:2192-265

Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria

CITATION: Van Zyl, W. F., Deane, S. M. & Dicks, L. M. T. 2020. Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria. Gut Microbes, 12(1):e1831339, doi:10.1080/19490976.2020.1831339.The original publication is available at https://www.tandfonline.comPublication of this article was funded by the Stellenbosch University Open Access FundGastrointestinal (GI) diseases, and in particular those caused by bacterial infections, are a major cause of morbidity and mortality worldwide. Treatment is becoming increasingly difficult due to the increase in number of species that have developed resistance to antibiotics. Probiotic lactic acid bacteria (LAB) have considerable potential as alternatives to antibiotics, both in prophylactic and therapeutic applications. Several studies have documented a reduction, or prevention, of GI diseases by probiotic bacteria. Since the activities of probiotic bacteria are closely linked with conditions in the host’s GI-tract (GIT) and changes in the population of enteric microorganisms, a deeper understanding of gut-microbial interactions is required in the selection of the most suitable probiotic. This necessitates a deeper understanding of the molecular capabilities of probiotic bacteria. In this review, we explore how probiotic microorganisms interact with enteric pathogens in the GIT. The significance of probiotic colonization and persistence in the GIT is also addressed.https://www.tandfonline.com/doi/full/10.1080/19490976.2020.1831339Publisher's versio

Second attempt to withdraw cabergoline in prolactinomas: a pilot study

According to Pituitary and Endocrine Society recommendations, cabergoline (CAB) therapy can be discontinued after 2 years in hyperprolactinemic patients who fit certain criteria. Previous studies found recurrence rates ranging between 26 and 69 %. Whether CAB therapy can be successfully discontinued after one unsuccessful withdrawal is unknown

Evidence of In Vivo Absorption of Lactate and Modulation of Short Chain Fatty Acid Absorption from the Reticulorumen of Non-Lactating Cattle Fed High Concentrate Diets.

Short-chain fatty acids (SCFAs) and lactate are endproducts of rumen fermentation and important energy sources for the host ruminant. Because their rapid accumulation results in ruminal acidosis, enhancement of the absorption of SCFA and lactate across reticuloruminal wall is instrumental in increasing energy supply and preventing ruminal acidosis in cattle. This study investigated whether the reticuloruminal absorption of SCFAs and lactate was altered by different strategies of high concentrate feeding. Eight rumen-cannulated, non-lactating Holstein cows were fed a forage-only diet (baseline) and then gradually adapted over 6 d to a 60% concentrate level. Thereafter, this concentrate-rich diet was fed for 4 wk either continuously (Con; n = 8) or interruptedly (Int; n = 8). Absorption of SCFAs and lactate was determined in vivo from the experimental buffer introduced into the washed reticulorumen. The buffer contained acetate, propionate, butyrate and lactate at a concentration of 60, 30, 10 and 5 mmol/L, respectively and Cr-EDTA as a marker for correcting ruminal water fluxes. The reticuloruminal absorption after 35 and 65 min of buffer incubation was measured at the baseline, after 1 wk of 60% concentrate feeding in the interrupted model (Int-1) and after 4 wk of concentrate feeding in both feeding models (Int-4 and Con-4). Data showed that the absorption rates of individual and total SCFAs during the first 35 min of incubation of Con-4 were highest (~1.7 times compared to baseline), while Int-1 and Int-4 were similar to respective baseline. Lactate was not absorbed during forage-only baseline and 1-wk concentrate feeding, but after 4-wk feeding of concentrates in both models. In conclusion, SCFAs absorption across the reticulorumen of non-lactating cattle was enhanced by the 4-wk continuous concentrate feeding, which seems to be more advantageous in terms of rumen acidosis prevention compared to the interrupted feeding model. The study provides evidence of lactate absorption across the reticulorumen of non-lactating cattle after both continuous and interrupted 4-wk concentrate feeding