Adequate combined therapy of acute rhinitis and sinusitis

Nasty days of autumn and winter, with their cold days, windy weather, rain and snow bring about a period of increased morbidity. It's not a secret that almost every cold is accompanied by an inflammatory ENT disease. Along with the wider availability of the Internet in the recent years, an increasing number of patients do not seek medical help but choose self-medication. This leads to frequent and often unjustified administration of antibacterial drugs, growth in the number of antibiotic-resistant strains of microorganisms, which finally results in higher incidence of chronic acute bacterial sinusitis and severe complications. On the other hand, clinical practitioners often "commit a sin" of prescribing a list of medications which do not always constitute a rational therapy, often ignoring the routine patient examination that would ensure accurate diagnosis. The purpose of this article is to recall the clinical pattern, diagnosis and current treatment schemes for acute rhinitis and sinusitis, to help us avoid certain mistakes in the future

Combined treatment of acute purulent sinusitis

Acute sinusitis is the most common condition in otorhinolaryngology [4]. Acute sinusitis adversely affects the quality of life and professional activity. Quite simple at first glance, the disease often leads to serious complications. Moreover, its treatment is associated with significant costs [5], making acute sinusitis one of the most relevant issues for otorhinolaryngology

A study of the efficacy and safety of local antibiotic treatment of acute purulent maxillary sinusitis

40 patients with acute purulent maxillary sinusitis underwent examination and treatment. This clinical trial demonstrated safety and efficacy of Dioxidine in punctures for acute purulent maxillary sinusitis

Protein Conformational Dynamics Underlie Selective Recognition of Thermophilic over Mesophilic Enzyme I by a Substrate Analogue

Substrate selectivity is an important preventive measure to decrease the possibility of cross interactions between enzymes and metabolites that share structural similarities. In addition, understanding the mechanisms that determine selectivity towards a particular substrate increases the knowledge base for designing specific inhibitors for target enzymes. Here, we combine NMR, molecular dynamics (MD) simulations, and protein engineering to investigate how two substrate analogues, allylicphosphonate (cPEP) and sulfoenolpyruvate (SEP), recognize the mesophilic (eEIC) and thermophilic (tEIC) homologues of the receptor domain of bacterial Enzyme I, which has been proposed as a target for antimicrobial research. Chemical Shift Perturbation (CSP) experiments show that cPEP and SEP recognize tEIC over the mesophilic homologue. Combined Principal Component Analysis of half-microsecond-long MD simulations reveals that incomplete quenching of a breathing motion in the eEIC–ligand complex destabilizes the interaction and makes the investigated substrate analogues selective toward the thermophilic enzyme. Our results indicate that residual protein motions need to be considered carefully when optimizing small molecule inhibitors of EI. In general, our work demonstrates that protein conformational dynamics can be exploited in the rational design and optimization of inhibitors with subfamily selectivity.This article is published as Singh, Aayushi, Daniel Burns, Sergey L. Sedinkin, Brett Van Veller, Davit A. Potoyan, and Vincenzo Venditti. "Protein Conformational Dynamics Underlie Selective Recognition of Thermophilic over Mesophilic Enzyme I by a Substrate Analogue." Biomolecules 13, no. 1 (2023): 160. DOI: 10.3390/biom13010160. Copyright 2023 by the authors. Attribution 4.0 International (CC BY 4.0). Posted with permission

Protein Conformational Dynamics Underlie Selective Recognition of Thermophilic over Mesophilic Enzyme I by a Substrate Analogue

Substrate selectivity is an important preventive measure to decrease the possibility of cross interactions between enzymes and metabolites that share structural similarities. In addition, understanding the mechanisms that determine selectivity towards a particular substrate increases the knowledge base for designing specific inhibitors for target enzymes. Here, we combine NMR, molecular dynamics (MD) simulations, and protein engineering to investigate how two substrate analogues, allylicphosphonate (cPEP) and sulfoenolpyruvate (SEP), recognize the mesophilic (eEIC) and thermophilic (tEIC) homologues of the receptor domain of bacterial Enzyme I, which has been proposed as a target for antimicrobial research. Chemical Shift Perturbation (CSP) experiments show that cPEP and SEP recognize tEIC over the mesophilic homologue. Combined Principal Component Analysis of half-microsecond-long MD simulations reveals that incomplete quenching of a breathing motion in the eEIC–ligand complex destabilizes the interaction and makes the investigated substrate analogues selective toward the thermophilic enzyme. Our results indicate that residual protein motions need to be considered carefully when optimizing small molecule inhibitors of EI. In general, our work demonstrates that protein conformational dynamics can be exploited in the rational design and optimization of inhibitors with subfamily selectivity