Therapy Of Infectious Diseases Research Articles

The effect of hypochlorous acid inhalation on the activity of antioxidant system enzymes in rats of different ages

Hypochlorous acid HOCl is an effective disinfectant with a broad spectrum and high rate of microbicidal action. Its use for air treatment can be an effective tool for the prevention and therapy of infectious diseases. In this work, the in vivo study was conducted on 110 Wistar Han rats (12 and 72 weeks old) on the effect of a single inhalation of air containing gaseous HOCl on the activity of antioxidant system enzymes. For this, a special installation was designed to uniformly maintain the concentration of HOCl in the air and regulate it over a wide range. Inhalation exposure was carried out for 4 h at total chlorine concentrations in the air of approximately 2.0 mg/m3 and 5.0 mg/m3, after which the animals were observed for 14 days. The effect of inhalation on the antioxidant system activity varied significantly in animals of different ages. Catalase activity in young rats increased approximately 2-fold on days 1-2 after inhalation, regardless of the HOCl concentration, while in old animals a sharp dose-dependent decrease was initially observed. The glutathione peroxidase activity in animals of both ages increased upon inhalation of air with 5.0 mg/m3 HOCl, and in old animals this was more pronounced; when the HOCl concentration decreased to 2.0 mg/m3, this indicator increased slightly in old rats and remained virtually unchanged in young ones. The glutathione reductase activity when exposed to 2.0 mg/m3 HOCl did not change for both age groups, and with increasing HOCl concentration it increased by 1.5-2.0 times in all animals.

Swarming Magnetic Fe3O4@Polydopamine-Tannic Acid Nanorobots: Integrating Antibiotic-Free Superficial Photothermal and Deep Chemical Strategies for Targeted Bacterial Elimination.

Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots (Fe3O4@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe3O4@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by insitu polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.

Total synthesis of [β-HIle]2-nodupetide: effect of ester to amide substitution on its antimicrobial activity.

The increasing prevalence of deaths due to multidrug-resistant bacteria (MDRB) in infectious disease therapy has become a global health concern. This led to the development of new antimicrobial therapeutic agents that can combat resistance to pathogenic bacteria. The utilization of natural peptide compounds as potential antimicrobial agents is very promising. Nodupetide, a cyclodepsipeptide with very strong antimicrobial activity against Pseudomonas aeruginosa was isolated from the fermentation of Nodulisporium sp. Unfortunately, one of its residues (3S,4S)-3-hydroxy-4-methylhexanoic acid (HMHA) is not commercially available and the synthesis strategies applied have not been successful. Hence, we synthesized its cyclopeptide analogue [β-HIle]2-nodupetide by replacing HMHA with isoleucine homologue. A combination of solid- and solution-phase peptide synthesis was successfully carried out to synthesize [β-HIle]2-nodupetide with an overall yield of 10.4%. The substitution of HMHA with β-homoisoleucine (β-HIle) changed the ester bond into an amide bond in nodupetide's backbone. The analogue was considerably inactive against Pseudomonas aeruginosa. It can be concluded that the ester bond is crucial for the antimicrobial activity of nodupetide.

Mesoporous silica nanoparticles: aversatile carrier platform in lung cancer management.

Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs'administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs'extraordinary therapeutic potential in fighting lung cancer as well as future hurdles.

Symptomatic therapy for acute infectious and inflammatory diseases of the pharynx

Symptomatic therapy for acute infectious and inflammatory diseases of the pharynx

Regional Antibiotic Resistance of the Main Uropathogens

The most important reason for the increase in mortality from infectious factors on the planet is the acquisition of resistance to antibacterial agents by microflora. Therefore, modern guidelines for the treatment of human infectious diseases recommend considering the regional sensitivity of the microflora when choosing an antibiotic. The treatment of infectious lesions of the urinary system is no exception, the disease of which is annually included in the list of the most frequent reasons for increasing the «burden of disease» on the planet. Therefore, the study of the microbial landscape of uropathogenic flora and its sensitivity to modern antibiotics in the Ukrainian population will contribute to increasing the effectiveness of treatment, especially empirical treatment, and reducing the antibiotic resistance of local uropathogens. The objective: optimization of the therapy of infectious and inflammatory diseases of the urinary system by considering the sensitivity of the main regional uropathogens to antibacterial agents. Materials and methods. Bacteriological research was carried out on 545 urine samples of symptomatic inpatients and outpatients aged 19 to 95 years, in whom pathological changes in urine sediment were determined during the examination. According to the sex distribution, women predominated in both groups in the ratio of 1.6:1 and 3.8:1, respectively. Identification of causative agents and their properties, as well as sensitivity to antibiotics, was carried out according to the standardized methods of domestic and international guidelines. The growth of microflora with the number of colony-forming units in 1 ml ≥ 104 (CFU/ml) was considered clinically significant. Statistical analysis was carried out with the help of the statistical package EZR v. 1.50. The critical level of significance is 0.05. Results. In urine samples obtained from patients of a multidisciplinary hospital, 81.7% of identified microorganisms were Escherichia coli (31.5%), Enterococcus faecalis (17.2%), Klebsiella spp. (16.2%), Candida albicans (6.6%), Acinetobacter species (5.6%) and Staphylococcus aureus (4.6%). In the outpatient group of patients, 92.1% of uropathogens were Escherichia coli (52.3%), Klebsiella spp. (13.6%), Staphylococcus aureus (13.6%), Enterococcus faecalis (8.0%) and Enterobacter sрp. (4.6%). In the spectrum of pathogens of infectious and inflammatory diseases of the urinary system, the role of microorganisms that form a capsule (Klebsiella spp., Acinetobacter sрp.) has been increasing in recent years: among the uropathogens in examined inpatients in 2013 (n=122) and 2022 (n=108) proportion of Klebsiella spp. increased, respectively, from 14.8% to 37%; and the proportion of Acinetobacter sрp. from 2.8% to 3.3%. The majority of uropathogens identified from the urine of patients of a multidisciplinary somatic hospital, in contrast to the outpatient group, was characterized by polyresistance to the action of antibacterial agents. Escherichia coli and Klebsiella spp. were sensitive only to fosfomycin and carbapenems, and Enterococcus faecalis – to fosfomycin, amoxicillin clavulonate, ampicillin sulbactam, vancomycin, meropenem and linezolid. Acinetobacter sрp. was insensitive to all antibiotics used in the study. The growth of fungi of the genus Candida albicans was inhibited by the main antifungal drugs of the «access» category – fluconazole, itraconazole, and ketoconazole, with a tendency toward a gradual increase in resistance, which was indicated by a significant number of moderately sensitive strains – 35, 25, and 10%, respectively. Conclusions. The spectrum of uropathogenic flora in patients of a multidisciplinary hospital is characterized by greater diversity and a more frequent combination of several types of microorganisms in one patient compared to the outpatient group. The most common causative agents of infectious and inflammatory diseases of the urinary tract in the Kyiv region are polyresistant strains of Escherichia coli, Enterococcus faecalis and Klebsiella spp. In the spectrum of pathogens of infectious and inflammatory diseases of the urinary system, the role of microorganisms that form a capsule (Klebsiella spp., Acinetobacter sрp.) has been increasing in recent years. Therefore, we are witnessing the evolutionary success of the protective mechanism of capsule formation, which is related, among other things, to the phenomenon of Bacterial Quorum Sensing in microorganisms and the formation of biofilms. Implementation of the obtained results of the study of regional sensitivity of uropathogens to antibacterial agents in medical practice will improve the results of treatment of infectious and inflammatory urological pathology and prevent the growth of antibiotic resistance of the local flora.

Group 3 innate lymphoid cells: A trained Gutkeeper.

Group 3 innate lymphoid cells (ILC3s) are tissue-resident immune lymphocytes that critically regulate intestinal homeostasis, organogenesis, and immunity. ILC3s possess the capacity to "sense" the inflammatory environment within tissues, especially in the context of pathogen challenges that imprints durable non-antigen-specific changes in ILC3 function. As such, ILC3s become a new actor in the emerging field of trained innate immunity. Here, we summarize recent discoveries regarding ILC3 responses to bacterial challenges and the role these encounters play in triggering trained innate immunity. We further discuss how signaling events throughout ILC3 ontogeny potentially control the development and function of trained ILC3s. Finally, we highlight the open questions surrounding ILC3 "training" the answers to which may reveal new insights into innate immunity. Understanding the fundamental concepts behind trained innate immunity could potentially lead to the development of new strategies for improving immunity-based modulation therapies for inflammation, infectious diseases, and cancer.

No time to die: Epigenetic regulation of natural killer cell survival.

NK cells are short-lived innate lymphocytes that can mediate antigen-independent responses to infection and cancer. However, studies from the past two decades have shown that NK cells can acquire transcriptional and epigenetic modifications during inflammation that result in increased survival and lifespan. These findings blur the lines between the innate and adaptive arms of the immune system, and suggest that the homeostatic mechanisms that govern the persistence of innate immune cells are malleable. Indeed, recent studies have shown that NK cells undergo continuous and strictly regulated adaptations controlling their survival during development, tissue residency, and following inflammation. In this review, we summarize our current understanding of the critical factors regulating NK cell survival throughout their lifespan, with a specific emphasis on the epigenetic modifications that regulate the survival of NK cells in various contexts. A precise understanding of the molecular mechanisms that govern NK cell survival will be important to enhance therapies for cancer and infectious diseases.

(280) Innovative Team Approach to Sexual Health Counseling; Partnership of Urology, Infectious Disease and Pelvic Floor Therapy to Increase Access to Care

Abstract Introduction Despite the prevalence and availability of HIV (Pre-exposure Prophylaxis i.e., PrEP), the number of new AIDS diagnoses continues to outpace treatment and prevention. Stigma, discrimination, lack of access continue to remain significant barriers in the prevention of new HIV infections, especially amongst vulnerable groups (i.e. LGBTQ, women, and minorities). We present a novel strategy to address a comprehensive approach to sexual health medicine through the partnership of Urology, Infectious Disease, and Pelvic Floor therapy. Objective Men who have sex with men (M2M) who either currently use or have an interests in use of pre-exposure prophylaxis (PrEP) continue to face barriers with respect to access to care, stigma, and or availability of effective partnerships to address and offer culturally competent care. The objective of this study is to assess attitudes and barriers to conventional and novel PrEP offerings as well as to present an innovative team approach between Urology, Infectious Disease (ID) Medicine and Pelvic Floor Therapy to offer a comprehensive multidisciplinary approach to treatment and care. Methods We enrolled 6 candidates (M2M) into our PrEP clinic which offers the Apretude (Cabotegivir 600 mg/3mL) injections. We conducted interviews, focused groups, and provided questionnaires to detail their experiences, beliefs, attitudes, barriers, and considerations for therapy. Results First, the preliminary results and findings of our study has shown that the needs, considerations, and beliefs of M2M is more varied, nuanced, and divergent with need to characterize, understand, and offer more specific culturally competent care in Sexual Health Medicine with respect to PrEP. Second, M2M designation does not exclude men from having sex with the opposite gender. These man preferred injectable PrEP option. Third, the partnership of Urology, Infectious Disease and Pelvic Floor Therapy reduced barriers, increased access to care, and decreased stigma as M2M felt more comfortable in the Urological setting. Conclusions M2M patients stated hesitancy, increased stigma and “shame” in going to ID for sexual health. Additionally, for M2M who have sexual partners of the opposite sex this would further increase stigma. Urology practices are accustomed to having discussions surrounding men’s sexual health with reduced stigma. The combination of Infectious Disease has presented an innovative partnership to discuss, prevent, and treat sexuallly transmited infections amongst M2M. Disclosure No.

Nanotechnology in the Diagnosis and Treatment of Antibiotic-Resistant Infections.

The development of antimicrobial resistance (AMR), along with the relative reduction in the production of new antimicrobials, significantly limits the therapeutic options in infectious diseases. Thus, novel treatments, especially in the current era, where AMR is increasing, are urgently needed. There are several ongoing studies on non-classical therapies for infectious diseases, such as bacteriophages, antimicrobial peptides, and nanotechnology, among others. Nanomaterials involve materials on the nanoscale that could be used in the diagnosis, treatment, and prevention of infectious diseases. This review provides an overview of the applications of nanotechnology in the diagnosis and treatment of infectious diseases from a clinician's perspective, with a focus on pathogens with AMR. Applications of nanomaterials in diagnosis, by taking advantage of their electrochemical, optic, magnetic, and fluorescent properties, are described. Moreover, the potential of metallic or organic nanoparticles (NPs) in the treatment of infections is also addressed. Finally, the potential use of NPs in the development of safe and efficient vaccines is also reviewed. Further studies are needed to prove the safety and efficacy of NPs that would facilitate their approval by regulatory authorities for clinical use.

Total synthesis of [β-HIle]2-nodupetide: effect of ester to amide substitution on its antimicrobial activity.

The increasing prevalence of deaths due to multidrug-resistant bacteria (MDRB) in infectious disease therapy has become a global health concern. This led to the development of new antimicrobial therapeutic agents that can combat resistance to pathogenic bacteria. The utilization of natural peptide compounds as potential antimicrobial agents is very promising. Nodupetide, a cyclodepsipeptide with very strong antimicrobial activity against Pseudomonas aeruginosa was isolated from the fermentation of Nodulisporium sp. Unfortunately, one of its residues (3S,4S)-3-hydroxy-4-methylhexanoic acid (HMHA) is not commercially available and the synthesis strategies applied have not been successful. Hence, we synthesized its cyclopeptide analogue [β-HIle]2-nodupetide by replacing HMHA with isoleucine homologue. A combination of solid- and solution-phase peptide synthesis was successfully carried out to synthesize [β-HIle]2-nodupetide with an overall yield of 10.4%. The substitution of HMHA with β-homoisoleucine (β-HIle) changed the ester bond into an amide bond in nodupetide's backbone. The analogue was considerably inactive against Pseudomonas aeruginosa. It can be concluded that the ester bond is crucial for the antimicrobial activity of nodupetide.

Analysis of Nanoparticles' Effects on Drug-Induced Psoriasis.

Psoriasis, an auto-inflammatory disorder, has major manifestations in the skin but can affect other organs. Currently, this condition has no cure, and the treatments include anti-inflammatory medications. Nanoparticles are widely used for drug delivery and have found successful applications in therapy for cancer and infectious diseases. Nanoparticles can also be used to deliver anti-inflammatory drugs to sites of inflammation. Moreover, some nanotechnology platforms possess intrinsic anti-inflammatory properties and may benefit the therapy of inflammation-driven disorders. Herein, we present a protocol to study nanotechnology concepts' anti-inflammatory properties in a chemically-induced psoriasis model.

A programmable and automated optical electrowetting-on-dielectric (oEWOD) driven platform for massively parallel and sequential processing of single cell assay operations.

Recently, there has been an increasing emphasis on single cell profiling for high-throughput screening workflows in drug discovery and life sciences research. However, the biology underpinning these screens is often complex and is insufficiently addressed by singleplex assay screens. Traditional single cell screening technologies have created powerful sets of 'omic data that allow users to bioinformatically infer biological function, but have as of yet not empowered direct functional analysis at the level of each individual cell. Consequently, screening campaigns often require multiple secondary screens leading to laborious, time-consuming and expensive workflows in which attrition points may not be queried until late in the process. We describe a platform that harnesses droplet microfluidics and optical electrowetting-on-dielectric (oEWOD) to perform highly-controlled sequential and multiplexed single cell assays in massively parallelised workflows to enable complex cell profiling during screening. Soluble reagents or objects, such as cells or assay beads, are encapsulated into droplets of media in fluorous oil and are actively filtered based on size and optical features ensuring only desirable droplets (e.g. single cell droplets) are retained for analysis, thereby overcoming the Poisson probability distribution. Droplets are stored in an array on a temperature-controlled chip and the history of individual droplets is logged from the point of filter until completion of the workflow. On chip, droplets are subject to an automated and flexible suite of operations including the merging of sample droplets and the fluorescent acquisition of assay readouts to enable complex sequential assay workflows. To demonstrate the broad utility of the platform, we present examples of single-cell functional workflows for various applications such as antibody discovery, infectious disease, and cell and gene therapy.

Применение препарата «Арбимектин» при комплексной терапии вирусных инфекций у собак и кошек

The presented scientific article describes the results of a study of the effectiveness of the drug «Arbimektin » in the complex treatment of viral infections in dogs and cats. It has been established that the tested antiviral drug «Arbimektin» in accordance with the instructions for use is effective in the complex therapy of infectious diseases of viral and bacterial etiology in animals, and is recommended for use in veterinary clinics for the purpose of: treatment in the complex therapy of infectious diseases of viral etiology in dogs ( adenovirus infections, parvovirus and coronavirus enteritis of dogs, parainfluenza), treatment in complex therapy of infectious diseases of viral and bacterial etiology in cats (panleukopenia, infectious rhinotracheitis, calicivirosis, chlamydia, mycoplasmosis).

Single-Impact Electrochemistry of Redox Liposomes for the Detection of Virulence Factors

Early detection of pathogens is a key factor for the successful therapy of infectious diseases. Some of the pathogenic bacteria involved in diseases interact with the host by producing compounds that are toxic or disruptive to the cells. As these virulence factors can be easier to spot than the pathogen, strategies of detection can be focused on these released compounds to identify the pathogenic bacterium.[1] Liposomes are vesicles composed of a lipid bilayer membrane, and as such are often used to mimic living cells. Here, the strategy consists in making redox liposomes by encapsulating an electroactive probe in their inner cavity, which will be detected at the electrode.[2] Virulence factors interacting with the vesicles increase the permeability of the lipid membrane and the contents of the liposomes are released over time. This redox probe is then detected with an electrode polarized at the appropriate potential. This work aims to study the single-impact electrochemistry of redox liposomes in different conditions. Previous results indicate that the addition of a surfactant to a liposomal suspension leads to their rupture when they stochastically collide with an ultramicroelectrode.[3] Similarly, virulence factors increase their release or electrolysis of contents upon impact with an ultramicroelectrode.[4] Chronoamperometry measurements recorded at the ultramicroelectrode polarized at the redox potential of the electrochemical probe show impact events (vesicle blocking) and opening events (vesicle reactor) when the encapsulated redox probe is released by the liposome, which are traced back to the presence of pathogenic bacteria.

RESEARCH REGARDING THE RESISTANCE PHENOTYPES OF BACTERIA ISOLATED FROM DOGS WITH RESPIRATORY TRACT INFECTIONS

The resistance phenotypes to animal pathogenic bacteria (both Gram-positive and Gram-negative bacteria) are increasing in frequency due to the use of antibiotic-based veterinary medicinal products in both in farm animals and pets. The research aimed to establish phenotypically the antibiotic resistance in bacterial strains isolated from dogs with various respiratory tract infections. Both susceptible Gram-positive and Gram-negative isolated strains had the highest frequency to enrofloxacin (82.45% and 81.81%). Gram-positive resistant strains had the highest frequency to penicillin G (70.18%), while Gram-negative strains had the highest frequency of resistance to lincomycin. The results confirm the marked increase of resistance phenotypes in both Gram-positive and Gram-negative strains to a wide range of antimicrobial substances, frequently used in the therapy of infectious diseases in dogs.

The healing Power of Light in the Prophylaxis and Therapy of infectious Diseases

The healing Power of Light in the Prophylaxis and Therapy of infectious Diseases

Pooling isolates to address the diversity in antimicrobial susceptibility of Pseudomonas aeruginosa in cystic fibrosis.

People with cystic fibrosis (pwCF) often suffer from chronic lung infections with Pseudomonas aeruginosa. While antibiotics are still commonly used to treat P. aeruginosa infections, there is a high discordance between in vitro and in vivo antibiotic efficacy, which contributes to suboptimal antibiotic therapy. In the present study, we found that isolates from the same sputum sample had highly diverse antibiotic resistance profiles [based on the minimal inhibitory concentration (MIC)], which may explain the reported discrepancy between in vitro and in vivo antibiotic efficacy. Through systematic analysis, we report that pooling nine isolates per sputum sample significantly decreased intrasample diversity in MIC and influenced clinical interpretation of antibiotic susceptibility tests compared to single isolate testing. Hence, pooling of isolates may offer a solution to obtain a consistent MIC test result and could lead to optimizing antibiotic therapy in pwCF and other infectious diseases where diversity in antibiotic resistance is observed.

Advantages of instant forms of antibiotics in the treatment of lower respiratory tract infections

Antibacterial drugs are the basis of pathogenetic therapy of most infectious diseases, including lower respiratory tract infections, which continue to occupy a leading place in the structure of morbidity and mortality from infectious diseases worldwide. At the same time, the continuing steady growth of antibiotic resistance of microorganisms, the problem of creating and developing new antibacterial drugs for use in outpatient practice determines the degree of importance of optimizing the dosage regimen of this group of drugs. According to domestic and foreign clinical recommendations, the drugs of choice for the treatment of lower respiratory tract infections in outpatient practice are aminopenicillins and inhibitor-protected penicillins. In the literature review of domestic and foreign studies, the advantages of instant forms of antibacterial drugs in the pharmacotherapy of lower respiratory tract infections are considered in detail and systematized. These include higher bioavailability of the drug, which provides an appropriate level of pharmacodynamic and clinical efficacy, a more favorable safety profile, ease of use in children and elderly patients, as well as in patients with impaired swallowing function, pharmacoeconomical advantages. Thus, the use of dispersible forms of antibacterial drugs in outpatient practice in the treatment of lower respiratory tract infections makes it possible to increase the effectiveness of pharmacotherapy, improve patient tolerance and adherence to treatment, which is especially important when taking medications independently, reduce treatment costs, which in combination helps to curb the development of antibiotic resistance.

ARPA-H Funds Two Cancer "Manhattan Projects".

The Advanced Research Projects Agency for Health (ARPA-H) recently announced two major cancer-related funding awards. One at Rice University will focus on implanting a small device that continuously monitors a patient's cancer and adjusts immunotherapy doses in real time. Another is going to Emory University to develop new ways to enhance the body's immune response toward therapies for cancers, autoimmune disorders, and infectious diseases.