Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

COVID-19 Biomarkers Comparison: Children, Adults and Elders.

Background and Objectives: this study aimed to research links between C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinekinase (CK), 25-OH vitamin D (25-OHD), ferritin (FER), high-density lipoprotein cholesterol (HDL)cholesterol and clinical severity in patients from the western part of Romania, and compare their potential use as biomarkers for intensive care units (ICU) admission and death in children, adults and elders. Materials and Methods: this study is a retrospective cohort study, performed on patients positively diagnosed with COVID-19. Available CRP, LDH, CK 25-OH vitamin D, ferritin, HDL cholesterol and clinical severity were recorded. The following were assessed: median group differences, association, correlation and receiver operating characteristic. Results: 381 children, 614 adults and 381 elders were studied between 1 March 2021 and 1 March 2022. Most children and adults presented mild symptomatology (53.28%, 35.02%, respectively), while most elders presented severe symptomatology (30.04%). ICU admission was 3.67% for children, 13.19% for adults and 46.09% for elders, while mortality was 0.79% for children, 8.63% for adults and 25.1% for elders. With the exception of CK, all other biomarkers showed some significant associations with clinical severity, ICU admission and death. Conclusions: CRP, LDH, 25-OH vitamin D, ferritin and HDL are important biomarkers for COVID-19 positive patients, especially in the pediatric population, while CK was mostly within normal ranges.

Methotrexate and Cetuximab-Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments.

Background Objectives: The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. Materials and Methods: The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). Results: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. Conclusions: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.

Insights into the Paulownia Shan tong (Fortunei × Tomentosa) Essential Oil and In Silico Analysis of Potential Biological Targets of Its Compounds.

The volatile composition of Paulownia Shan tong (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% v/w) from flowers (forestry wastes) was investigated by gas chromatography-mass spectrometry. Thirty-one components were identified, with 3-acetoxy-7, 8-epoxylanostan-11-ol (38.16%), ß-monoolein (14.4%), lycopene, 1,2-dihydro-1-hydroxy- (10.21%), and 9,12-octadecadienoic acid, 2-phenyl-1,3-dioxan-5-yl ester (9.21%) as main compounds. In addition, molecular docking was employed to identify potential protein targets for the 31 quantified essential oil components. Inhibition of these targets is typically associated with antibacterial or antioxidant properties. Molecular docking revealed that six of these components, namely, 13-heptadecyn-1-ol, ascabiol, geranylgeraniol, anethole, and quinol dimethyl ether, outperformed the native ligand (hypoxanthine) of xanthine oxidase in terms of theoretical binding affinity, therefore implying a significant in silico inhibitory potential against xanthine oxidase. These findings suggest that the essential oil extracted from Paulownia Shan tong flowers could be valuable for developing protein-targeted antioxidant compounds with applications in the food, pharmaceutical, and cosmetic industries.

Host-Guest Complexation of Itraconazole with Cyclodextrins for Bioavailability Enhancement.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.

Two Antibiotics, Ampicillin and Tetracycline, Exert Different Effects in HT-29 Colorectal Adenocarcinoma Cells in Terms of Cell Viability and Migration Capacity.

Antibiotics are considered the cornerstone of modern medicine; however, currently, antibiotic resistance has become a global health issue. Antibiotics also find new uses in the treatment of other pathologies as well as cancer. The present study aimed to verify the impact of tetracycline and ampicillin in a colorectal adenocarcinoma cell line, HT-29. The effects of the two antibiotics on cell viability and nucleus were evaluated by the means of MTT assay and the Hoechst staining method, respectively. The irritant potential at vascular level of the chorioallantoic membrane was tested by the HET-CAM assay. Treatment of HT-29 cells with the two antibiotics determined different effects: (i) tetracycline induced a dose- and time-dependent cytotoxic effect characterized by decreased cell viability, changes in cells morphology, apoptotic features (nuclear fragmentation), and inhibition of cellular migration, whereas (ii) ampicillin exerted a biphasic response-cytotoxic at low doses and proliferative at high concentrations. In terms of effect on blood vessels, both antibiotics exerted a mild irritant effect. These results are promising and could be considered as starting point for further in vitro studies to define the molecular mechanisms involved in the cytotoxic/proliferative effects.

Chemical Composition, In Vitro and In Silico Antioxidant Potential of Melissa officinalis subsp. officinalis Essential Oil.

The investigation aimed to study the in vitro and in silico antioxidant properties of Melissa officinalis subsp. officinalis essential oil (MOEO). The chemical composition of MOEO was determined using GC-MS analysis. Among 36 compounds identified in MOEO, the main were beta-cubebene (27.66%), beta-caryophyllene (27.41%), alpha-cadinene (4.72%), caryophyllene oxide (4.09%), and alpha-cadinol (4.07%), respectively. In vitro antioxidant properties of MOEO have been studied in 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging, and inhibition of ß-carotene bleaching assays. The half-maximal inhibitory concentration (IC50) for the radical scavenging abilities of ABTS and DPPH were 1.225 ± 0.011 µg/mL and 14.015 ± 0.027 µg/mL, respectively, demonstrating good antioxidant activity. Moreover, MOEO exhibited a strong inhibitory effect (94.031 ± 0.082%) in the ß-carotene bleaching assay by neutralizing hydroperoxides, responsible for the oxidation of highly unsaturated ß-carotene. Furthermore, molecular docking showed that the MOEO components could exert an in vitro antioxidant activity through xanthine oxidoreductase inhibition. The most active structures are minor MOEO components (approximately 6%), among which the highest affinity for the target protein belongs to carvacrol.

[Gram-positive cocci isolated from urocultures of ambulatory and hospitalized patients with surgical risk]. / Coci Gram-pozitivi izolati din uroculturi provenite din ambulator si sectii cu risc chirurgical.

OBJECTIVES: We propose a comparative study of sensitivity to antibiotics of Gram-positive germs isolated in urocultures from patients in ambulatory and two wards with surgical risk (urology and obstetrics-gynaecology), and also to establish the resistance phenotypes of these strains. MATERIAL AND METHOD: 124 strains of Gram-positive cocci were studied: 28 S. aureus strains, 24 strains of coagulase-negative staphylococcus (CNS), 23 Streptococcus aglactiae strains, 1 Streptococcus anginosus strain and 48 Enterococcus spp. strains. The isolated strains came from 4398 urocultures (1889--ambulatory, 1871--urology, 629--obstetrics-gynaecology). Testing of antibiotic sensitivity was performed through Kirby-Bauer disk-diffusion method, with automatic phenotyping (Osiris Evolution system). RESULTS: In ambulatory, the wild phenotype was predominant in all isolated strains (33.33% S. aureus, 50% CNS, 100% Streptococcus aglactiae, 60% Enterococcus spp.). In the urology ward, the following multiresistant strains were isolated: 9 MRSA strains (47.36%), 1 MRSE strain (100%), 1 VRE strain (4.34%). In the obstetrics-gynaecology ward, 7 strains showed multiple antibiotic resistance: 4 MRSA strains (66.66%), 2 MRSE strains (50%), 1 VRE strain (6.66%). CONCLUSIONS: Multiresistant strains were isolated in hospital environment, which can be explained by the improper use of antibiotics, the instrumental approach of the urinary tract, and the existence of risk factors in the patients admitted in the above-mentioned wards. Enforcement of efficient nosocomial infection control measures is advisable, as well as a policy for rational antibiotic use.

[Aminoglycoside resistance of enterobacteria isolated from urinary infections in surgical departments]. / Rezistenta la aminoglicozide a enterobacteriilor izolate din infectii urinare în sectii cu profil chirurgical.

The aim of the study was to determine the aminoglycosides resistance of Enterobacteriaceae strains isolated from urocultures. Identification of the germs was performed by the API system (BioMerieux) and susceptibility tests was performed by disk-diffusion test (CLSI standards) and with API strips. For detecting the resistance to aminoglycosides we used gentamicin, tobramycin, netilmicin and amikacin. From 2500 urine samples we isolated 673 microbial strains, from which 531 were Enterobacteriaceae, especially E. coli, 57.62% and Klebsiella pneumoniae pneumoniae, 27.68% strains. We observed natural maintained sensibility to aminoglycosides at 55.17% from all the strains we have studied The high prevalence of aminoglycosides resistance of Enterobacteriaceae strains is explained by prolonged antibiotic therapy of patients with invasive diagnostic and therapeutic procedures. A rational policy in prescribing antibiotics in this department is therefore mandatory.

[Phenotypic characterization of Streptococcus agalactiae strains isolated from urocultures]. / Caracterizarea fenotipica a unor tulpini de Streptococcus agalactiae izolate din uroculturi.

UNLABELLED: The aim of this study was to determine the antibiotic resistance of Streptococcus agalactiae strains isolated from urocultures in order to obtain new data regarding circulating phenotypes in Urology Department. METHODS: For identifications of Streptococcus agalactiae strains we used Pastorex Strep (BioRad). The sensitivity of isolated germs to antimicrobials was tested using standardised Kirby-Bauer technique. RESULTS: We isolated 21 Streptococcus agalactiae strains from 1871 urocultures. Analyzing the extended antibiograms we categorized these germs according with their resistance phenotypes and we remarked a high percentage of wild type phenotype Streptococcus agalactiae strains (80.95%). CONCLUSIONS: Streptococcus agalactiae strains are more rarely isolated from hospital acquired urinary tract infections, that's way we can explain the low resistance of these strains.

[Antibiotic resistance patterns in Acinetobacter spp. strains isolated from hospital environment]. / Pattern-uri de rezistenta la antibiotice ale unor tulpini de Acinetobacter spp. izolate din mediul spitalicesc.

INTRODUCTION: The Acinetobacter species are ubiquitary germs isolated more and more frequently, Acinetobacter baumannii being currently considered the second strictly aerobic microorganism involved in the ethiology of severe nosocomial infections. Acinetobacter baumannii is usually encountered in surgery and intensive care units, especially in patients with depressed immunity, in which various locations are possible, the most frequvent being the respiratory tract infections, urinary tract infections and bacteriemia. MATERIAL AND METHOD: The study used 52 strains of Acinetobacter spp. isolated from 1131 biological samples (bronchial aspirat, urine, wound secretion, blood, pus, CFS) obtained from the patients of the Timisoara Country Hospital. Identification of germs was performed using the API (BioMerieux) system, and the antibiotics sensitivity testing was made by disk diffusion testing (Kirby-Bauer), with automatic reading and phenotyping through the Osiris Evolution (BioRad) system. RESULTS: The study of resistance to beta-lactamines has pointed out the predominance of penicillinase and cephalosporinase producing strains, 55.77% of the tested ones being part of this phenotype. 90.38% of the strains were resistant to one or more aminoglycosides. Of the tested strains 76.93% were resistant to fluoroquinolones, 86.54% to trimethoprim-sulphamethoxazole, and only 21.15% to tethracycline. CONCLUSIONS: Among the emerging pathogens involved in the nosocomial infections, Acinetobacter baumannii strains have become, in the past decades, a real health issue, due to the variety and seriousness of clinical symptoms. Through the constant increase of the cases number, and the difficulty of applying an effective treatment, the above-mentioned strains showed a multiple resistance to antibiotics.

[Phenotype characterisation of Enterococcus spp. strains isolated from urocultures]. / Caracterizarea fenotipica a unor tulpini de Enterococcus spp. izolate din uroculturi.

OBJECTIVES: Our aim is to comparatively study the susceptibility to antibiotics of Enterococcus spp. strains isolated from urocultures of patients admitted in the urology department, as well as from ambulatory patients, and also to establish the resistance phenotypes of these strains. MATERIALS AND METHODS: We studied 33 strains of Enterococcus spp.: 10 isolated from a total of 1889 urocultures from ambulatory patients (of which 431 positive) and 23 isolated from 1871 urocultures from patients admitted in the urology department (of which 462 positive). The antibiotic susceptibility was realised by Kirby-Bauer disk-diffusion tests. Statistical analysis of the antibiograms and determining of the resistance phenotypes were performed with automatic reading methods (Osiris--Bio Rad Laboratories), according to the CLSI/NCCLS standard. RESULTS: The wild phenotype was present in 60% of the strains isolated from ambulatory patients, and only in 39.13% in patients admitted in the urology department. In the urology department a multiresistant strain was isolated, displaying Van A (VRE) phenotype, to which was added resistance to beta-lactams, aminoglycosides, macrolides, tetracycline and nitrofurans. CONCLUSIONS: In the past decades urinary tract infections with Enterococcus spp., especially the nosocomial ones, have become serious health issues because of the increasing number of cases and the difficulty of treatment of infections caused by multi-resistant strains. In order to limit the spread of these strains, especially VRE strains, in the hospital environment, efficient measures must be instituted for the control of nosocomial infections, accompanied by policies for the rational use of antibiotics.

The establishment of resistance phenotypes for bacteria isolated from outpatients in urine cultures.

From 1911 outpatients, who addressed a Timisoara private clinical laboratory, from January to December 2005, we collected 1,889 urine cultures, 431 being positive. Bacteria identification was generally done using morphological, cultural, biochemical characters and pathogenicity tests. Sensitivity testing to antimicrobial medical drugs was done by using the classical diffusion Kirby-Bauer method and the automatic analyzer Osiris, also. The main bacteria involved in the etiology of these infections were represented by Enterobacteriaceae, head of the list being Escherichia coli (81.21%), followed by Klebsiella pneumoniae (8.35%) and Proteus mirabilis (3.02%). We also isolated Gram positive cocci (in a much smaller proportion), mainly represented by Enterococcus faecalis (1.16%), Staphylococcus aureus (0.93%), Streptococcus agalactiae, and also Gram negative non-fermentative bacilli, such as Pseudomonas aeruginosa (0.93%) or Acinetobacter baumanii (0.23%). As soon as we performed the sensitivity tests, we divided them in resistance phenotypes: Most of the Enterobacteriaceae were integrated in the wild phenotype, followed by the penicillinase producing phenotype. An E. coli strain (0.29%) and 3 Klebsiella pneumoniae strains (8.33%) were integrated in the large spectrum, multidrug resistant, beta-lactamase producing phenotype, also associated with resistance to fluoroquinolones and aminoglycosides; Non-fermentative bacilli did not present special resistance problems, the four Pseudomonas aeruginosa strains were integrated in the wild phenotype (secreting induced chromosomal cephalosporinase). As for Staphylococcus aureus it was identified a strain having fluoroquinolone resistance, two strains secreting penicillinase and having a K (Nm) phenotype and a strain secreting penicillinase only. Antibiotic resistance represents a major concern for patients, physicians, healthcare managers, and policymakers. The use of antibiotics is closely linked with the development of acquired antibiotic resistance.