Biocompatible Self-Assembled Hydrogen-Bonded Gels Based on Natural Deep Eutectic Solvents and Hydroxypropyl Cellulose with Strong Antimicrobial Activity.

Natural deep eutectic solvents (NADES)-hydroxypropyl cellulose (HPC) self-assembled gels with potential for pharmaceutical applications are prepared. FT-IR, 1HNMR, DSC, TGA and rheology measurements revealed that hydrogen bond acceptor−hydrogen bond donor interactions, concentration of NADES and the water content influence significantly the physico-chemical characteristics of the studied gel systems. HPC-NADES gel compositions have thermal stabilities lower than HPC and higher than NADES components. Thermal transitions reveal multiple glass transitions characteristic of phase separated systems. Flow curves evidence shear thinning (pseudoplastic) behavior. The flow curve shear stress vs. shear rate were assessed by applying Bingham, Herschel−Bulkley, Vocadlo and Casson rheological models. The proposed correlations are in good agreement with experimental data. The studied gels evidence thermothickening behavior due to characteristic LCST (lower critical solution temperature) behavior of HPC in aqueous systems and a good biocompatibility with normal cells (human gingival fibroblasts). The order of antibacterial and antifungal activities (S.aureus, E.coli, P. aeruginosa and C. albicans) is as follows: citric acid >lactic acid > urea > glycerol, revealing the higher antibacterial and antifungal activities of acids.

Adipokines, and not vitamin D, associate with antibody immune responses following dual BNT162b2 vaccination within individuals younger than 60 years.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to a global health outbreak known as the COVID-19 pandemic which has been lasting since March 2020. Vaccine became accessible to people only at the beginning of 2021 which greatly helped reducing the mortality rate and severity of COVID-19 infection afterwards. The efficacy of vaccines was not fully known and studies documenting the immune responses following vaccination are continuing to emerge. Recent evidence indicate that natural infection prior vaccination may improve the antibody and cellular immune responses, while little is known about the factors influencing those processes. Here we investigated the antibody responses following BNT162b2 vaccination in relation to previous-infection status and age, and searched for possible biomarkers associated with the observed changes in immune responses. We found that the previous-infection status caused at least 8-times increase in the antibody titres, effect that was weaker in people over 60 years old and unaltered by the vitamin D serum levels. Furthermore, we identified adiponectin to positively associate with antibody responses and negatively correlate with pro-inflammatory molecules (MCP-1, factor D, CRP, PAI-1), especially in previously-infected individuals.

A Real Pandora's Box in Pandemic Times: A Narrative Review on the Acute Cardiac Injury Due to COVID-19.

The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

Mucoadhesive and Antimicrobial Allantoin/ß Cyclodextrins-Loaded Carbopol Gels as Scaffolds for Regenerative Medicine.

Allantoin and its ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin inclusion complexes 1:1 have been used to prepare carbopol-based mucoadhesive gels. The gelation process occurred by adjustment with glycerol 10% in the presence of triethanolamine. The structural features induced by the presence of allantoin and the corresponding ß-cyclodextrins inclusion complexes have been first investigated by infrared spectroscopy highlighting strong interactions within the gels network and ideal crosslinks for the self-healing behavior. The hydrophilicity of the gels was investigated by the determination of the surface tension parameters and the free energy of hydration. The interfacial free energy values indicated prolonged biocompatibility with blood. The gels-water molecule interactions in terms of sorption, permeability, and diffusion coefficients were evaluated by dynamic vapor sorption analysis. The self-assembly process through intermolecular H-bonding, the high hydrophilicity, the mechanical performance, the hydrolytic stability in simulated biological media, the biocompatibility with normal human dermal fibroblast (NHDF) cells, the mucoadhesivity and antimicrobial activity on selected microorganism species (S. Aureus and C. albicans) of the allantoin-based gels recommend them as promising scaffold alternatives in regenerative medicine.

Preparation and Antimicrobial Activity of Chitosan and Its Derivatives: A Concise Review.

Despite the advantages presented by synthetic polymers such as strength and durability, the lack of biodegradability associated with the persistence in the environment for a long time turned the attention of researchers to natural polymers. Being biodegradable, biopolymers proved to be extremely beneficial to the environment. At present, they represent an important class of materials with applications in all economic sectors, but also in medicine. They find applications as absorbers, cosmetics, controlled drug delivery, tissue engineering, etc. Chitosan is one of the natural polymers which raised a strong interest for researchers due to some exceptional properties such as biodegradability, biocompatibility, nontoxicity, non-antigenicity, low-cost and numerous pharmacological properties as antimicrobial, antitumor, antioxidant, antidiabetic, immunoenhancing. In addition to this, the free amino and hydroxyl groups make it susceptible to a series of structural modulations, obtaining some derivatives with different biomedical applications. This review approaches the physico-chemical and pharmacological properties of chitosan and its derivatives, focusing on the antimicrobial potential including mechanism of action, factors that influence the antimicrobial activity and the activity against resistant strains, topics of great interest in the context of the concern raised by the available therapeutic options for infections, especially with resistant strains.

Design, Preparation and Evaluation of HPMC-Based PAA or SA Freeze-Dried Scaffolds for Vaginal Delivery of Fluconazole.

PURPOSE: Aim of this work was preparation of bioadhesive gel formulations based on Hydroxypropyl methylcellulose (HPMC), Poly(acrylic acid) (PAA) or Sodium alginate (SA) loaded with anise/fluconazole ß-cyclodextrin inclusion complexes in 1:2 and 1:3 ratios intended for vaginal applications. METHODS: Freeze-drying method was effectively utilized and superporous morphology was obtained. The superporous morphology of the lyophilized gels, dynamic water vapor sorption measurements, drug release kinetics studies and their antimicrobial activities are presented. RESULTS: HPMC content influences especially the sorption/desorption behaviour of HPMC-based PAA gels and the morphology of the gel formulations with fluconazole/ß-cyclodextrin inclusion complexes, due to the interactions among the gel networks absorbing water molecules. It was found that fluconazole release kinetics correspond to quasi-Fickian, Fickian diffusion and non-Fickian mechanisms for the studied hydrogels. The tested vaginal formulations with ß-cyclodextrin inclusion complexes exhibited selectivity toward S. aureus ATCC 25923 and all tested Candida strains in comparison with the gel formulation without ß-cyclodextrin. CONCLUSIONS: The fluconazole/ß cyclodextrin inclusion complexes ensure a controlled release of fluconazole over a few days, the highest amount of drug release (92%) being observed after 43 h. These bioadhesive gel formulations could be very promising topical alternative for treatment of vaginal fungal infections.

Characterization of MRSA strains by phenotypic and OCR-based methods.

With the emergence and spread of new methicilin resistant Staphylococcus aureus (MRSA) strains, control of dissemination, both in hospitals and in the community, requires the molecular characterization of the circulating strains in order to establish their dynamics and identify the sources of infection. During this study we analyzed the MRSA isolates by means of PCR-based methods in order to improve epidemiological surveillance and early application of prevention measures. The presence of mecA, nuc, lukF-PV and lukS-PV genes, as well as SCCmec types was assessed in relation to clinical characteristics and multidrug resistance (MDR) for 86 MRSA isolates and showed that 51% of MDR strains were carriers of mobile genetic elements SCCmec IV and the majority of non-MDR SCCmec type IV strains were PVL-positive (81.8%). Comparison of diagnostic methods showed that PBP2 detection represents an extremely useful alternative to PCR for the rapid screening of MRSA isolates, in laboratories that lack facilities necessary for molecular diagnosis, such as PFGE (Pulse Field Gel Electrophoresis), spa-typing and/or MLST (Multilocus Sequence Typing).

Detection of Aminoglycoside and Macrolide Resistance Mechanisms in Methicillin-Resistant Staphylococcus Aureus.

Methicillin-resistant Staphylococcus aureus can become resistant to many different classes of antibiotics. Objective: To characterize aminoglycoside and macrolide resistance mechanisms in MRSA strains in relation to antibiotic susceptibility patterns. Materials and methods: We tested 86 MRSA strains using multiplex PCR for detection of genes mecA, aac(6')-Ie/aph(2″), ant(4')-Ia, aph(3')-IIIa, ermA, ermC and msrA. Results: There was a prevalence of msrA (32.5%), ermC (30.2%) and aph(3')-IIIa (61.6%) genes, which are less frequently reported in MRSA. Most msrA genes was detected in PVL positive strains (92.8%) and was associated only with non-MDR strains, while ermC genes were associated with MDR strains. PVL producing strains were characterized by the presence of aph(3')-IIIa (93.1%) and msrA genes (93.1%), being phenotypically susceptible to clindamycin. Conclusions: Detection of aminoglycoside and macrolide resistance genes allowed us to establish the concordance between genotypic and phenotypic methods and to correlate the presence of certain resistance genes with the type of circulating strain and the production of virulence factors.

ANTIBIOTIC RESISTANCE SPECTRUM OF NON FERMENTING GRAM NEGATIVE BACILLI ISOLATED IN THE ORTHOPEDIC TRAUMATOLOGY CLINIC OF "SF. SPIRIDON" CLINICAL EMERGENCY HOSPITAL IASI.

AIM: The retro-prospective analysis of antibiotic sensitivity of non-fermenting gram negative bacilli strains circulating in the Orthopedics-Traumatology Clinic from "Sf. Spiridon" Emergency Clinical Hospital in view of determining the trend of the resistance phenomenon and indicating the most useful treatment for the infections caused by these strains. MATERIAL AND METHODS: The retrospective component was conducted from 01.01.2003 to 31.12.2012, and the result of the diffusimetric antibiograms was taken from the hospital's informatics system; the prospective component of the study involved the collection of pathological products from the patients admitted during January-December 2013, who showed clinical suspicion of infection, in compliance with the general collection norms for the products destined for the bacteriological exam. RESULTS: From the total 167 strains of Pseudomonas aeruginosa isolated and identified from the patients, 48 (28.74%) were sensitive to at least one antibiotic from each tested class, 29 (17.39%) were resistant to a single antibiotic and the rest of 90 (53.89%) showed multiple resistance. We noticed a statistically significant difference between the number of strains sensitive to at least one antibiotic from each tested class and those with multiple resistance (p < 0.05). For the strains of Acinetobacter baumanii combined resistance was identified for 121 (87.04%), out of which 55 (39.56%) were resistant to two classes of antibiotics and the other (47.48%) to all three classes. The most frequently met was the association of resistance to quinolones and aminoglycosides, namely for a number of 49 strains (35.25%); only 3.59% of them were simultaneously sensitive to the three classes of antibiotics. CONCLUSION: The already high percentages and the rising trends of antibiotic resistance of non-fermenting gram-negative bacteria described in this study confirm the continuous decrease of the efficiency of antimicrobial agents and underline the necessity of a global strategy which aims at all health sectors regarding the rational use of antibiotics, on the one hand, and the continuation of studies concerning the surveillance of the antimicrobial resistance phenomenon, on the other hand.

Analysis of antibiotic resistance pattern of S. aureus strains isolated from the Orthopedics-Traumatology Section of "Sf. Spiridon" Clinical Emergency Hospital, Iasi.

AIM: The retrospective analysis of antibiotic sensibility of S. aureus strains isolated from infected patients from the Orthopedics-Traumatology Clinic of "Sf. Spiridon" Clinical Emergency Hospital, Iasi during January 2003-December 2013, in view of determining the evolution trend of the resistance phenomenon and of pinpointing the most useful treatment for these strains. MATERIAL AND METHOD: The antibiotic sensitivity test was carried out using two methods: diffusimetric-Kirby-Bauer and the MIC determination by E-test (for the strains isolated in 2013); the interpretation of the sensitivity was made in a standardized manner, in compliance with the CLSI (Clinical and Laboratory Standards Institute) standard for antibiotics testing in force. RESULTS: The sensitivity testing for beta-lactams proved that during the 11 years of the study, the average value of the frequency of resistant strains was of 41.59% +/- 8.68. The highest frequency of MRSA (Methicillin Restant S. aureus) strains was noticed in 2012 (58.6%), followed by 2004 (50.7%). Even if in 2013 it dropped to 38.9%, the trend calculated for 2003-2013 is slightly rising (y = 0.0073x + 0.372). Out of the total of 495 S. aureus strains that were isolated, 164 (33.13%) were completely sensitive to the tested antibiotics and 26 (5.25%) were resistant only to beta-lactams. The other MRSA strains associated multiple resistance and MIC for vancomycin varied between 0.5-2 mg/ml. Two strains whose MIC was of 0.5 mg/ml were sensitive to most classes of tested antibiotics, including beta-lactams, except for macrolides (erythromycin), and the strain whose MIC was of 2 mg/ml, was resistant to all classes of tested antibiotics, except for glycopeptides and oxazolidiones. The other tested strains had a MIC for vancomycin equal to 1 mg/ml. CONCLUSIONS: Due to the fact that there are infections with SAMR strains in a rather worrying percentage (53.9%) that are resistant to the other classes of antibiotics, the only therapeutic solution being the vancomycin treatment, its use should be limited solely to those cases when it is really necessary. Fortunately, no vancomycin resistant MRSA strains have been identified in our country, but this phenomenon should be kept under close surveillance.

Retrospective study on the etiological spectrum and antibiotic resistance in infections associated with osteosynthesis materials.

AIM: To determine the prevalence of infections according to their etiologic spectrum and antibiotic sensitivity in patients with or without implants and endoprostheses. MATERIAL AND METHODS: This retrospective study was conducted based on a customized study protocol on 773 cases admitted to the Clinic of Orthopedics - Traumatology of the Iasi "Sf. Spiridon" Emergency Hospital in the interval January 1, 2003 - December 31, 2011 for postoperative infectious complication. RESULTS: S. aureus was more frequently found in the patients without implant (58.2%) and in those with subcutaneous implant (45.5%); the lowest frequency was noticed in the patients with endoprosthesis (27.1%), the frequency distributions showing marked statistically significant differences (p = 0.001). P. aeruginosa was more frequently detected in the patient group with endoprosthesis (30.2%), while in the other groups it was found in approximately 7% (p = 0.001). The presence of Acinetobacter spp. was significantly higher in patients with deep implant (12.9%), with the lowest frequency noticed in the patients without implant (4.5%) (p = 0.029). Of the total isolated and identified types, 59.6% were non-multidrug-resistant (non-MDR), the remaining 40.4% being MDR types. CONCLUSIONS: S. aureus was the most frequent etiological agent in patients with or without cutaneous implant (45.5 and 58.2%, respectively), and P. aeruginosa (30.2%) in the endoprosthesized patients. Implementation of a preoperative screening protocol for the identification of healthy S. aureus carriers (Methicillin-sensitive S. aureus - MSSA/Methicillin-resistant S. aureus - MRSA) and subsequent decolonization would be an efficient way of reducing the incidence of infections caused by this bacterium.

Polyurethane/ß-cyclodextrin/ciprofloxacin composite films for possible medical coatings with antibacterial properties.

Polyurethane/ß-cyclodextrin/ciprofloxacin composite films have been prepared and structural and morphological behaviours reveal the progressive incorporation of the drug ciprofloxacin into polyurethane backbones. Spectral changes such as frequency shifts, band broadening and changes in the intensity are indicative of drug-polyurethane interactions. X-ray powder diffraction experiments demonstrate that ciprofloxacin retains its crystallinity in the polyurethane matrix. Electron microscopy and mercury porosimetry reveal open and interconnected macroporous pore morphology for the as-prepared polyurethane-drug films. Antimicrobial activity was evaluated by the agar disc diffusion method and the ciprofloxacin-polyurethane films demonstrate their potency as antibacterial medical systems. However, the ciprofloxacin-polyurethane films do not reveal antifungal properties.