Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target.

Lipid II is an essential glycolipid found in bacteria. Accessing this valuable cell wall precursor is important both for studying cell wall synthesis and for studying/identifying novel antimicrobial compounds. Herein, we describe optimizations to the modular chemical synthesis of lipid II and unnatural analogues. In particular, the glycosylation step, a critical step in the formation of the central disaccharide unit (GlcNAc-MurNAc), was optimized. This was achieved by employing the use of glycosyl donors with diverse leaving groups. The key advantage of this approach lies in its adaptability, allowing for the generation of a wide array of analogues through the incorporation of alternative building blocks at different stages of synthesis.

Xanthan gum and pectin as beverage stabilizers reduce the digestive enzyme hydrolysis of antioxidant and antihypertensive peptides obtained from a brewery byproduct.

An acidic beverage was formulated with xanthan gum (XG), pectin (P) and brewer spent grain (BSG) peptides with antioxidant and antihypertensive properties. The impact of hydrocolloids levels on peptide bioaccessibility was studied. Peptides were obtained from BSG using Purazyme and Flavourzyme enzymes. BSG peptides were fractionated by ultrafiltration (UF) and four fractions were obtained: F1 (>10 kDa), F2 (10-5 kDa), F3 (1-5 kDa), and F4 (<1 kDa). F3 showed the highest protein purity, ferulic acid content, proportion of amphipathic peptides, and bioactive properties (ABTS+ radical scavenging and ACE-I inhibitory activity). The identified peptides from F3 by tandem mass spectrometry were 138. In silico analysis showed that 26 identified peptides had ABTS+ inhibitory activity, while 59 ones presented good antihypertensive properties. The effect of XG and P levels on bioaccessibility of F3 peptides in the formulated beverages was studied by a central composite experimental design. It was observed that F3 peptides interacted with hydrocolloids by electrostatic forces at pH of formulated beverages. The addition of hydrocolloids to formulation modulated the release of the antioxidant peptides and protected the degradation of ACE-I inhibitory peptides from F3 during simulated gastrointestinal digestion. Finally, the level of hydrocolloids that produced intermediate viscosities in the formulated beverages improved the bioaccessibility of the F3 peptides.

Aflibercept, ranibizumab and bevacizumab upcoming biosimilars: a general overview.

Anti-vascular endothelial growth factors currently are the first-line treatment option for neovascular age-related macular degeneration (nAMD) and other retinal vascular disorders, and their clinical use is associated with high financial burden. Biosimilars are a type of biological product highly similar to referral biologic drugs; they are increasing competition among biologics and have the potential to reduce the overall expenditures on biologics. In this comprehensive literature review, the current investigational biosimilars acting on retinal diseases are discussed. The authors review the results of clinical studies and highlight ongoing trials. Several biosimilar candidates are under evaluation and the pipeline will rapidly change in the future, as soon as each patent expires. Clinicians have to know these new therapeutic agents, which might come in the mainstream clinical practice as a more cost-efficient option.

Excimer laser trabeculotomy vs 180 degrees selective laser trabeculoplasty in primary open-angle glaucoma. A 2-year randomized, controlled trial.

PURPOSE: To compare the effectiveness and safety of excimer laser trabeculotomy (ELT) ab interno vs selective laser trabeculoplasty (SLT) over 24 months of follow-up in patients with primary open-angle glaucoma (POAG) refractory to medical therapy. PATIENTS AND METHODS: This prospective, randomized study included 30 consecutive eyes assigned randomly to either ELT or SLT group. ELT was carried out using a XeCl Excimer Laser with an emission wavelength of 308 nm. Eight spots were equally distributed at a distance of 500 microm from one another over the anterior trabeculum. The SLT patients were treated with a frequency-doubled q-switched neodymium:yytrium-aluminum-garnet laser (wavelength 532 nm). Approximately 50 adjacent, but not overlapping, laser spots were distributed over 180 degrees of the trabecular meshwork, using an energy level ranging from 0.7 to 1.0 mJ per pulse. The main outcome measure was intraocular pressure (IOP) lowering after ELT and SLT. Success was defined as >or=20% reduction in IOP without further glaucoma intervention. RESULTS: At 24 months, complete success rates were 53.3% for the ELT group and 40% for the SLT group (P=0.35, Fisher's exact test); qualified success rates were 33.3% for the ELT and 26.6% for the SLT group (P=0.5, Fisher's exact test).Mean IOP decreased from 25.0+/-1.9 to 17.6+/-2.2 mmHg (-29.6%; P<0.0001) in the ELT group and from 23.9+/-0.9 to 19.1+/-1.8 mmHg (-21%; P<0.0001) in the SLT group. CONCLUSIONS: Both ELT and SLT proved to be effective techniques in the treatment of POAG refractory to medical therapy.