Metabolic Syndrome and Cardiac Vessel Remodeling Associated with Vessel Rarefaction: A Possible Underlying Mechanism May Result from a Poor Angiogenic Response to Altered VEGF Signaling Pathways.

BACKGROUND: Elevated mortality rates in patients with metabolic syndrome (MetS) are partly due to adverse remodeling of multiple organs, which may lead to cardiovascular disease, nonalcoholic fatty liver disease, kidney failure, or other conditions. MetS symptoms, such as obesity, hypertension, hyperglycemia, dyslipidemia, associated with insulin and leptin resistance, are recognized as major cardiovascular risk factors that adversely affect the heart. SUMMARY: Pathological cardiac remodeling is accompanied by endothelial cell dysfunction which may result in diminished coronary flow, dysregulated oxygen demand/supply balance, as well as vessel rarefaction. The reduced number of vessels and delayed or inhibited formation of collaterals after myocardial infarction in MetS heart may be due to unfavorable changes in endothelial cell metabolism but also to altered expression of vascular endothelial growth factor molecules, their receptors, and changes in signal transduction from the cell membrane, which severely affect angiogenesis. KEY MESSAGES: Given the established role of cardiac vessel endothelial cells in maintaining tissue homeostasis, defining the molecular background underlying vessel dysfunction associated with impaired angiogenesis is of great importance for future therapeutic purposes. Therefore, the aim of this paper was to present current information regarding vascular endothelial growth factor signaling in the myocardium of MetS individuals.

In Vitro Cytotoxicity, Colonisation by Fibroblasts and Antimicrobial Properties of Surgical Meshes Coated with Bacterial Cellulose.

Hernia repairs are the most common abdominal wall elective procedures performed by general surgeons. Hernia-related postoperative infective complications occur with 10% frequency. To counteract the risk of infection emergence, the development of effective, biocompatible and antimicrobial mesh adjuvants is required. Therefore, the aim of our in vitro investigation was to evaluate the suitability of bacterial cellulose (BC) polymer coupled with gentamicin (GM) antibiotic as an absorbent layer of surgical mesh. Our research included the assessment of GM-BC-modified meshes' cytotoxicity against fibroblasts ATCC CCL-1 and a 60-day duration cell colonisation measurement. The obtained results showed no cytotoxic effect of modified meshes. The quantified fibroblast cells levels resembled a bimodal distribution depending on the time of culturing and the type of mesh applied. The measured GM minimal inhibitory concentration was 0.47 µg/mL. Results obtained in the modified disc-diffusion method showed that GM-BC-modified meshes inhibited bacterial growth more effectively than non-coated meshes. The results of our study indicate that BC-modified hernia meshes, fortified with appropriate antimicrobial, may be applied as effective implants in hernia surgery, preventing risk of infection occurrence and providing a high level of biocompatibility with regard to fibroblast cells.

In Vitro Efficacy of Bacterial Cellulose Dressings Chemisorbed with Antiseptics against Biofilm Formed by Pathogens Isolated from Chronic Wounds.

Local administration of antiseptics is required to prevent and fight against biofilm-based infections of chronic wounds. One of the methods used for delivering antiseptics to infected wounds is the application of dressings chemisorbed with antimicrobials. Dressings made of bacterial cellulose (BC) display several features, making them suitable for such a purpose. This work aimed to compare the activity of commonly used antiseptic molecules: octenidine, polyhexanide, povidone-iodine, chlorhexidine, ethacridine lactate, and hypochlorous solutions and to evaluate their usefulness as active substances of BC dressings against 48 bacterial strains (8 species) and 6 yeast strains (1 species). A silver dressing was applied as a control material of proven antimicrobial activity. The methodology applied included the assessment of minimal inhibitory concentrations (MIC) and minimal biofilm eradication concentration (MBEC), the modified disc-diffusion method, and the modified antibiofilm dressing activity measurement (A.D.A.M.) method. While in 96-well plate-based methods (MIC and MBEC assessment), the highest antimicrobial activity was recorded for chlorhexidine, in the modified disc-diffusion method and in the modified A.D.A.M test, povidone-iodine performed the best. In an in vitro setting simulating chronic wound conditions, BC dressings chemisorbed with polyhexanide, octenidine, or povidone-iodine displayed a similar or even higher antibiofilm activity than the control dressing containing silver molecules. If translated into clinical conditions, the obtained results suggest high applicability of BC dressings chemisorbed with antiseptics to eradicate biofilm from chronic wounds.

Comparison of the new flexible tip bougie catheter and standard bougie stylet for tracheal intubation by anesthesiologists in different difficult airway scenarios: a randomized crossover trial.

BACKGROUND: Incidence of difficult endotracheal intubation ranges between 3 and 10%. Bougies have been recommended as an airway adjunct for difficult intubation, but reported success rates are variable. A new generation flexible tip bougie appears promising but was not investigated so far. We therefore compared the new flexible tip with a standard bougie in simulated normal and difficult airway scenarios, and used by experienced anesthesiologists. METHODS: We conducted a observational, randomized, cross-over simulation study. Following standardized training, experienced anesthesiologists performed endotracheal intubation using a Macintosh blade and one of the bougies in six different airway scenarios in a randomized sequence: normal airway, tongue edema, pharyngeal obstruction, manual cervical inline stabilization, cervical collar stabilization, cervical collar stabilization and pharyngeal obstruction. Overall success rate with a maximum of 3 intubation attempts was the primary endpoint. Secondary endpoints included number of intubation attempts, time to intubation and dental compression. RESULTS: Thirty-two anesthesiologist participated in this study between January 2019 and May 2019. Overall success rate was similar for the flexible tip bougie and the standard bougie. The flexible tip bougie tended to need less intubation attempts in more difficult airway scenarios. Time to intubation was less if using the flexible tip bougie compared to the standard bougie. Reduced severity of dental compression was noted for the flexible tip bougie in difficult airway scenarios except cervical collar stabilization. CONCLUSION: In this simulation study of normal and difficult airways scenarios, overall success rate was similar for the flexible tip and standard bougie. Especially in more difficult airway scenarios, less intubation attempts, and less optimization maneuvers were needed if using the flexible tip bougie. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03733158. 7th November 2018.

Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight against Helicobacter pylori Lawn Biofilm.

Helicobacter pylori is a bacterium known mainly of its ability to cause persistent inflammations of the human stomach, resulting in peptic ulcer diseases and gastric cancers. Continuous exposure of this bacterium to antibiotics has resulted in high detection of multidrug-resistant strains and difficulties in obtaining a therapeutic effect. The purpose of the present study was to determine the usability of bacterial cellulose (BC) chemisorbed with 3-bromopyruvate (3-BP) or sertraline (SER) to act against lawn H. pylori biofilms. The characterization of BC carriers was made using a N2 adsorption/desorption analysis, tensile strength test, and scanning electron microscopy (SEM) observations. Determination of an antimicrobial activity was performed using a modified disk-diffusion method and a self-designed method of testing antibacterial activity against biofilm microbial forms. In addition, bacterial morphology was checked by SEM. It was found that BC disks were characterized by a high cross-linking and shear/stretch resistance. Growth inhibition zones for BC disks chemisorbed with 2 mg of SER or 3-BP were equal to 26.5-27.5 mm and 27-30 mm, respectively. The viability of lawn biofilm H. pylori cells after a 4-h incubation with 2 mg SER or 3-BP chemisorbed on BC disks was ≥4 log lower, suggesting their antibacterial effect. SEM observations showed a number of morphostructural changes in H. pylori cells exposed to these substances. Concluding, SER and 3-BP chemisorbed on BC carriers presented a promising antibacterial activity against biofilm H. pylori cells in in vitro conditions.

Application of flow cytometry in diagnosing lymphomas in dogs and cats.

Classification of types of lymphomas is done by interpreting cell morphology results obtained in cytological and/or histological examinations. In recent years, additional methods like immunocytochemistry (ICC), immunohistochemistry (IHC), immunophenotyping by flow cytometry and polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR), have been used to diagnose and classify lymphomas. Unfortunately, none of these methods is completely specific and sensitive. Thus, a combination of several diagnostic methods or use of all available techniques allows for evaluation of morphological properties of cells like their maturity and diversification. Owing to the use of sets of antibodies it is possible to identify the phenotype of hyperplastic cells as well as their origin. Combination of results obtained through phenotypical analysis with flow cytometry examination with morphological, histological and genetic testing enables a detailed analysis of, in this case, lymphoproliferative diseases including reaction changes, primary and secondary immunological deficits as well as autoimmune diseases.

Bioelectrical activity of porcine oviduct and uterus during spontaneous and induced estrus associated with cyclic hormone changes.

It is widely accepted that uterine contraction is initiated by spontaneous generation of electrical activity at a cellular level in the form of action potentials. Such action potential events, when they involve many myometrial cells and occur in immediate succession, are described by their amplitude and duration. In an effort to improve clinical management of uterine contractions, research has focused on determination of the properties of the reproductive tract's electrical activity under hormonal stimulation. The aim of this study was to evaluate the myoelectric activity (amplitude and duration) of the oviduct and the uterus in relation to plasma concentration of LH, estradiol (E2), and progesterone (P4) during spontaneous and induced estrus in gilts. The course of the experiment was divided into eight periods defined by hormone concentrations (LH, P4, and E2) and time intervals before and after the start of the LH surge. Myoelectric signals were recorded, and the hormone levels were measured during proestrus and estrus in natural and hormone-induced estrus cycle. During the natural estrus, the LH surge was longer than after hormonal stimulation (28 vs. 20 hours) and suggested an inverse relationship between the LH concentration and the duration of myoelectric activity (SR = -0.68). Analyses of the records of the amplitudes and durations of the electromyography activity in uterine horns and oviducts showed significant differences between spontaneous and induced estrus (P < 0.05). During induced estrus, the LH surge began earlier (T1 vs. T2) and increased more (7.46 vs. 6.50 ng/mL) than during spontaneous estrus. This observation suggests a direct relationship between the LH concentration and the amplitude of the myoelectric activity (Spearman rank correlation = 0.71). The significantly higher duration and amplitude of the activity in the isthmus of the oviduct and the uterus during induced estrus shortly after the onset of standing heat (4-8 hours after the LH surge) suggested more favorable conditions for effective artificial insemination.

Biodistribution and Efficacy Studies of the Proteasome Inhibitor BSc2118 in a Mouse Melanoma Model.

Inhibition of the proteasome offers many therapeutic possibilities in inflammation as well as in neoplastic diseases. However, clinical use of proteasome inhibitors is limited by the development of resistance or severe side effects. In our study we characterized the anti-tumor properties of the novel proteasome inhibitor BSc2118. The sensitivity of tumor lines to BSc2118 was analyzed in comparison to bortezomib using crystal violet staining in order to assess cell viability. The In Vivo distribution of BSc2118 in mouse tissues was tracked by a fluorescent-modified form of BSc2118 (BSc2118-FL) and visualized by confocal microscopy. Inhibition of the 20S proteasome was monitored both in cultured cell lines and in mice, respectively. Finally, safety and efficacy of BSc2118 was evaluated in a mouse melanoma model. BSc2118 inhibits proliferation of different tumor cell lines with a similar potency as compared with bortezomib. Systemic administration of BSc2118 in mice is well tolerated, even when given in a dose of 60 mg/kg body weight. After systemic injection of BSc2118 or bortezomib similar proteasome inhibition patterns are observed within the murine organs. Detection of BSc2118-FL revealed correlation of distribution pattern of BSc2118 with inhibition of proteasomal activity in cells or mouse tissues. Finally, administration of BSc2118 in a mouse melanoma model shows significant local anti-tumor effects. Concluding, BSc2118 represents a novel low-toxic agent that might be alternatively used for known proteasome inhibitors in anti-cancer treatment.