ABSTRACT
The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term memory recurrent neural network (LSTM RNN). To assess their antimicrobial effect, we synthesized five out of 198 generated peptides. The PEP-38 and PEP-137 peptides were active in vitro against carbapenem-resistant isolates of Klebsiella aerogenes and K. pneumoniae. PEP-137 was also active against Pseudomonas aeruginosa. The remaining three peptides (PEP-36, PEP-136 and PEP-174) showed no antibacterial effect. Then the effect of PEP-38 and PEP-137 (a single intraperitoneal administration of a 100 µg dose 30 min after infection) on animal survival in an experimental murine model of K. pneumoniae-induced sepsis was investigated. As a control, two groups of mice were used: one received sterile saline, and the other received inactive in vitro PEP-36 (a single 100 µg dose). The PEP-36 peptide was shown to provide the highest survival rate (66.7%). PEP-137 showed a survival rate of 50%. PEP-38 was found to be ineffective. The data obtained can be used to develop new antibacterial peptide drugs to combat antibiotic resistance.
ABSTRACT
The absence of effective drugs for COVID-19 prevention and treatment requires the search for new candidates among approved medicines. Fundamental studies and clinical observations allow us to approach an understanding of the mechanisms of damage and protection from exposure to SARS-CoV-2, to identify possible points of application for pharmacological interventions. In this review we presented studies on the anti-inflammatory, antioxidant, and immunotropic properties of melatonin. We have attempted to present scientifically proven mechanisms of action for the potential therapeutic use of melatonin during SARS-CoV-2 infection. A wide range of pharmacological properties allows its inclusion as an effective addition to the methods of prevention and treatment of COVID-19.
ABSTRACT
Antimicrobial resistance is one of the key issues limiting the successful treatment of infectious diseases and associated with adverse medical, social and economic consequences on a global scale. The present study aims to evaluate antimicrobials prescribing patterns and assess progress in quality indicators in Russian multidisciplinary hospitals using three repetitive point prevalence studies (PPSs) over 4 years (Global-PPS 2015, 2017 and 2018). Out of 13,595 patients from 21 hospitals surveyed over the three time points, 3542 (26.14%) received antimicrobials, predominantly third-generation cephalosporins (44.7% in 2015, 34.1% in 2017 and 41.8% in 2018). Compliance with the hospital antibiotic guidelines was 74.8%, 66.8% and 74.3%, respectively. Indication for treatment was recorded in 72.6%, 84.1% and 82.6%, while stop/review date was documented only in 40.5%, 46.5% and 61.1% of cases. Perioperative antibiotic prophylaxis exceeded 1 day in 92%, 84% and 81% of cases. Targeted therapy rate at all time points did not exceed 15.1%, treatment based on the biomarkers rate-19.9%. For the part of PPS-2017 and 2018 analyzed in dynamics, no prominent trends were noted. The results of the project provide the basis for the development of appropriate antimicrobial stewardship programs tailored according to local practices for each hospital in the project.
ABSTRACT
The search for osteoinductive as well as osteoconductive materials has led to the novel idea of using titanium in bone augmentations of the alveolar crest. Due to its excellent biocompatibility and favorable osteogenic properties, highly porous TiO2 granules has been proposed as a promising material for non-resorbable synthetic bone grafts in the restoration of large bone defects, and for bone augmentation in dental applications. OBJECTIVES: The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to the maxillary sinus in sheep. The experimental animal study involved 15 yearling sheep with a focus on the osteogenic potential of porous titanium used for subantral augmentation. MATERIAL AND METHODS: Calibrated defects were prepared in the subantral region of sheep. The defects were randomized into tests and control group. The test defects were grafted with porous titanium granules (PTG), whereas control defects were left empty (sham). Defects were left for healing for 30, 60, and 90 days. After healing, the grafted areas were removed and finally osteoconductivity was analyzed by an orthopantograph (OPG} and histology. RESULTS: Significantly more new bone formed in PTG grafted defects compared with sham. The control group showed significantly less expression of key inflammation cells, but with no significant difference in key inflammation cells compared with the experimental groups. CONCLUSION: Porous titanium can offer as an effective alternative to calcium phosphate and bone collagen-based materials used for subantral augmentation of the maxillary bone in cases of dental implantation.
