Clinical usefulness of a host signature based on TRAIL, IP10, and CRP (MeMed BV) as infection biomarkers in intensive care units' patients. A retrospective observational study.

INTRODUCTION: Infection complications are common in intensive care unit patients, and early detection remains a diagnostic challenge. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers. A novel diagnostic approach focuses on the host immune response. One of the approaches, the MMBV index, is based on measuring in a blood sample three parameters: (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), (ii) interferon-γ-induced protein-10 (IP10), and (iii) CRP. This study aimed to evaluate the usefulness of MMBV as an infection biomarker in an ICU cohort. PATIENTS AND METHODS: Forty-six patients treated in the University Clinical Center in Gdansk ICU were enrolled in the study, and their clinical data were retrospectively analyzed. In total, 91 MMBV results were analyzed. RESULTS: Most of the patients had high MMBV values, suggesting bacterial etiology. A weak correlation between PCT and MMBV was observed, and no correlation between parameter changes was noted. There was a correlation between CRP/MMBV and between changes in CRP / changes in MMBV. CONCLUSION: It seems that MMBV is not valuable for ICU patients neither in diagnosing nor monitoring infection. Higher MMBV values may predict unfavorable treatment outcomes.

The Impact of Continuous Veno-Venous Hemodiafiltration on the Efficacy of Administration of Prophylactic Doses of Enoxaparin: A Prospective Observational Study.

BACKGROUND: Critically ill patients frequently require continuous renal replacement therapy (CRRT). During CRRT, particles up to 10 kDa in size, such as enoxaparin, may be removed. The aim of this study was to determine if patients receiving prophylactic doses of enoxaparin and treated with continuous veno-venous hemodiafiltration (CVVHDF) reach prophylactic values of anti-Xa factor activity. METHODS: In this observational trial, we compared two groups: 20 patients treated with CVVHDF and 20 patients not treated with CVVHDF. All of them received prophylactic doses of 40 mg of enoxaparin subcutaneously. Anti-Xa factor activity was determined on the third day of receiving a prophylactic dose of enoxaparin. The first blood sample was taken just before the administration of enoxaparin, and other samples were taken 3 h, 6 h, and 9 h after the administration of a prophylactic dose of enoxaparin. RESULTS: At 3 and 6 h after administration of enoxaparin in both groups, we observed a significant increase in anti-Xa factor activity from baseline, with the peak after 3 h of administration. There were no significant differences in the numbers of patients who had anti-Xa factor activity within the prophylactic range between CVVHDF and control groups. CONCLUSION: CVVHDF has only a mild effect on the enoxaparin prophylactic effect measured by anti-Xa factor activity. Thus, it seems there is no need to increase the dose of enoxaparin for patients requiring CVVHDF.

Perioperative carbohydrate loading in patients undergoing one-day surgery. A systematic review of randomized controlled trials.

Introduction: It is suggested that preoperative carbohydrate loading may have beneficial effects, which is emphasised in Enhanced Recovery After Surgery protocols (ERAS). Recent data confirmed that carbohydrate loading shortens length of hospital stay. Aim: In this systematic review we aimed to determine whether carbohydrate loading have positive effects in patients undergoing 1-day surgery. Material and methods: We searched 5 databases and identified some randomized controlled trials which were reviewed independently by two reviewers. In the end 6 RCTs were included, involving 411 patients. Studies compared effects of carbohydrate loading vs. fasting and/or placebo on the following outcomes: thirst, hunger, postoperative nausea and vomiting (PONV), fatigue, pain and postoperative insulin resistance. In most cases data are inconclusive as studies reported opposite results. Conclusions: It seems that carbohydrate loading did not have a significant impact when compared to fasting or placebo. Preoperative carbohydrate loading seems not to have significant benefits over fasting or placebo in patients qualified for 1-day surgery.

Fluoride enhances polystyrene nanoparticles cytotoxicity in colonocytes in vitro model.

Human gastrointestinal cells can be exposed to different xenobiotics present in food or drinking water. In this work, we assessed the cytotoxicity of polystyrene nanoparticles (PS-NPs) and how it is impacted by fluoride (F-) presence. We decided to examine PS-NPs and F- which can be easily found in drinking water and food. Commercially available amine-modified 100 nm PS-NPs were used in the study. Scanning Electron Microscopy with Electron Dispersive Spectroscopy (SEM-EDS) and Dynamic Light Scattering (DLS) were used to characterize PS-NPs. The colon cell lines (HT-29, Caco-2, CCD 841 CoN) were used. Cytotoxicity of PS-NPs and F- alone or in co-exposition were assessed with MTT assay in a time- and concentration-dependent manner. Flow cytometry was used to measure reactive oxygen species (ROS) production, cell cycle distribution, and apoptosis analysis. Transmission electron microscopy (TEM) was used to determine whether PS-NPs and/or F- can cause ultrastructure changes in the cells. We have shown that PS-NPs are cytotoxic to human colon cells in a time- and concentration-dependent manner. PS-NPs did not impact neither intracellular ROS production nor the cells cell cycle distribution. However, if HT-29 cells were co-exposed to PS-NPs and F-, an increased number of cells in G0/G1 phase and decreased number of cells in G2/M were observed. PS-NPs can cause apoptosis in HT-29 cells, this effect was enhanced if cells were co-exposed to PS-NP and F-. PS-NPs were internalised by the cells and caused ultrastructure changes. Fluoride itself (1 mM) was not cytotoxic to the cells and did not cause any changes in the ultrastructure of the cells. We have proven that polystyrene nanoparticles can be cytotoxic to human gastrointestinal cells and this effect is enhanced by fluoride.

Effect of Carbohydrate-Enriched Drink Compared to Fasting on Hemodynamics in Healthy Volunteers. A Randomized Trial.

Fasting prior to surgery can cause dehydration and alter hemodynamics. This study aimed to determine the impact of a carbohydrate-enriched drink (NutriciaTM Pre-op®) on selected hemodynamical parameters, measured in a non-invasive manner. We enrolled 100 healthy volunteers and measured their weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), thoracic fluid content (TFC), thoracic fluid index (TFCI), stroke volume (SV), stroke volume variation (SVV), stroke index (SI), cardiac output (CO), cardiac index (CI), heather index (HI), systolic time ration (STR), systemic time ratio index (STRI), systemic vascular resistance (SVR), and systemic vascular resistance index (SVRI) by a Niccomo™ device, implementing the impedance cardiography (ICG) method. Measurements were performed at the beginning of the study, and after 10 h and 12 h. We randomly allocated participants to the control group and the pre-op group. The pre-op group received 400 mL of Nutricia™ preOp®, as suggested in the ERAS guidelines, within 10 h of the study. Student's t-test or the Mann-Whitney U test were used to compare the two groups, and p < 0.05 was considered significant. We did not observe any changes in hemodynamical parameters, blood pressure, and heart rate between the groups. We have proven that carbohydrate-enriched drink administration did not have a significant impact on the hemodynamical parameters of healthy volunteers.

Silver Nanoparticles as Chlorhexidine and Metronidazole Drug Delivery Platforms: Their Potential Use in Treating Periodontitis.

PURPOSE: Periodontal disease (PD), defined as oral inflammation caused by dental plaque, is an emerging problem. PD may lead to tooth loss, and treatment options are limited. In this study, we designed, synthesized, and characterized silver nanoparticles (AgNPs) conjugated with chlorhexidine (AgNPs-CHL) or metronidazole (AgNPs-PEG-MET) to determine whether they can be used to treat PDs. MATERIALS AND METHODS: AgNPs were synthesized and characterized by transmission electron microscopy, UV-vis spectrometry, thermogravimetric analyses, and dynamic light scattering. We determined the safety and the antimicrobial and anti-inflammatory properties of synthesized AgNPs in an in vitro model of periodontitis. Antimicrobial properties were determined by measuring the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) on reference strains of bacteria and fungi. Human gingival fibroblast (HGF-1), murine macrophage (RAW264.7) and human foetal osteoblast (hFOB1.19) cells were used in the study. Lipopolysaccharide (LPS) was used to induce inflammation. Cytokine levels were measured using an enzyme-linked immunosorbent assay; metalloproteinase expression was measured using Western blotting. RESULTS: The synthesized AgNPs were spherical and narrow-dispersed with an average diameter of 13.4 nm ± 3.0 nm in the case of AgNPs-CHL and 3.72 nm ± 0.72 nm in the case of AgNPs-PEG-MET. Both types of AgNPs were active against bacteria and fungi. AgNPs-CHL proved to be a more potent antimicrobial agent, although they were more cytotoxic than AgNPs-PEG-MET; however, both demonstrated beneficial properties in nontoxic concentrations. AgNPs-CHL and AgNPs-PEG-MET decreased the production of proinflammatory cytokines IL-1ß, IL-6, IL-8 and TNFα. Both agents also decreased the levels of metalloproteinases MMP3 and MMP8, which may indicate that they will inhibit tissue degradation. CONCLUSION: AgNPs-CHL and AgNPs-PEG-MET may be possible therapeutic options for PD, as they have antibacterial and anti-inflammatory properties. However, to fully understand the potential of AgNPs, our in vitro findings must be evaluated in an in vivo model.

The influence of fasting and carbohydrate-enriched drink administration on body water amount and distribution: a volunteer randomized study.

BACKGROUND: Fasting prior to anesthesia is considered aspiration prophylaxis. However, prolonged food and drink restrictions may increase the risk of other complications. The aim of this study was to assess whether a carbohydrate-enriched drink (Nutricia™ preOp®), recommended by the enhanced recovery after surgery (ERAS) protocol, can improve body hydration in fasting healthy individuals. METHODS: Measurements were done with the bioelectric impedance analysis with a Fresenius body composition monitor. Body composition, total body water, water distribution, and hemodynamic parameters were measured at the beginning of the study and after 10 h and 12 h of fasting. Patients fasted for 10 h and then were divided into two groups: the control (n = 40) and the pre-op group (n = 41). The pre-op group received 400 mL of Nutricia™ preOp®, as suggested in the ERAS guidance. The two-tailed Student's t test was used to compare two groups with normally distributed data and homogenous variances; if variances were heterogeneous, Welch's test was used. The Mann-Whitney U test was used to compare two groups with non-normal data distribution. p < 0.05 was considered statistically significant. RESULTS: We found no significant differences between the control and pre-op groups regarding body water distribution and body composition. We did not observe significant losses in the total body water after fasting. Also, blood pressure was not affected by fasting. CONCLUSION: We have proven that pre-op did not impact either body composition or body water. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04665349 . Registered on 11 December 2020-retrospectively registered.

Modified Nanoparticles as Potential Agents in Bone Diseases: Cancer and Implant-Related Complications.

Materials sized 1-100 nm are the nanotechnology's field of interest. Because of the unique properties such as the ability to penetrate biological barriers and a high surface to volume ratio, nanoparticles (NPs) are a powerful tool to be used in medicine and industry. This review discusses the role of nanotechnology in bone-related issues: osteosarcoma (bone cancer), the biocompatibility of the implants and implant-related infections. In cancer therapy, NPs can be used as (I) cytotoxic agents, (II) drug delivery platforms and (III) in thermotherapy. In implant-related issues, NPs can be used as (I) antimicrobial agents and (II) adjuvants to increase the biocompatibility of implant surface. Properties of NPs depend on (I) the type of NPs, (II) their size, (III) shape, (IV) concentration, (V) incubation time, (VI) functionalization and (VII) capping agent type.

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics.

Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and high-performance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast- hFOB1.19, breast cancer cells - MCF7, breast epithelial cells - MCF10A, pancreatic cancer cells - PANC-1, and pancreatic cells - hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

Shape-Depended Biological Properties of Ag3PO4 Microparticles: Evaluation of Antimicrobial Properties and Cytotoxicity in In Vitro Model-Safety Assessment of Potential Clinical Usage.

Implant-related infections are an emerging clinical and economic problem. Therefore, we decided to assess potential clinical usefulness and safety of silver orthophosphate microparticles (SOMPs) regarding their shape. We synthesized and then assessed antimicrobial properties and potential cytotoxicity of six shapes of SOMPs (tetrapod, cubes, spheres, tetrahedrons, branched, and rhombic dodecahedron). We found that SOMPs had a high antimicrobial effect; they were more efficient against fungi than bacteria. SOMPs exerted an antimicrobial effect in concentrations not toxic to mammalian cells: human fetal osteoblast (hFOB1.19), osteosarcoma (Saos-2), mouse preosteoblasts (MC3T3-E1), skin fibroblast (HDF), and mouse myoblast (C2C12). At higher concentration SOMPs, induced shape- and concentration-dependent cytotoxicity (according to MTT and BrdU assays). Tetrapod SOMPs had the smallest effect, whereas cubical SOMPs, the highest on cell viability. hFOB1.19 were the most resistant cells and C2C12, the most susceptible ones. We have proven that the induction of oxidative stress and inflammation is involved in the cytotoxic mechanism of SOMPs. After treatment with microparticles, we observed changes in levels of reactive oxygen species, first-line defense antioxidants-superoxide dismutase (SOD1, SOD3), and glutathione peroxidase (GPX4), metalloproteinase (MMP1, MMP3), and NF-κB protein. Neither cell cycle distribution nor ultrastructure was altered as determined by flow cytometry and transmission electron microscopy, respectively. In conclusion, silver orthophosphate may be a safe and effective antimicrobial agent on the implant surface. Spherical-shaped SOMPs are the most promising for biomedical application.

Impact of gold nanoparticles shape on their cytotoxicity against human osteoblast and osteosarcoma in in vitro model. Evaluation of the safety of use and anti-cancer potential.

Due to development of nanotechnology and gold nanoparticles (AuNPs) increasing use in different areas of medicine, especially in oncology, better understanding of their potential cytotoxicity is necessary to protect patients safety. Shape and size of AuNPs is an important modulator of their cytotoxicity. Therefore, we investigated the cytotoxicity of AuNPs rods (≈39 nm length, 18 nm width), AuNPs stars (≈ 215 nm) and AuNPs spheres (≈ 6.3 nm) against human fetal osteoblast (hFOB 1.19), osteosarcoma (143B, MG63) and pancreatic duct cell (hTERT-HPNE) lines by MTT and neutral-red uptake assay. Moreover, influence of AuNPs on level of proapoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) was measured by western blot. Cellular uptake of nanoparticles and ultrastructure changes were examined by transmission electron microscopy (TEM). In the present study we have proven that AuNPs stars are the most cytotoxic against human cells. We observed that cancer cells are more susceptible to AuNPs cytotoxic effect. Furthermore, AuNPs rods and AuNPs stars caused increased expression of Bax and decreased expression of Bcl-2 protein in osteosarcoma cells. We found that AuNPs penetrated through the cell membrane and caused ultrastructural changes. Our results clearly demonstrated that the cytotoxicity of AuNPs was shape-dependent. AuNPs stars with the highest anti-cancer potential were also the most cytotoxic type of tested NPs, whereas AuNPs spheres which appears to be the safest one had small anti-cancer potential.

Nerve growth factor as an important possible component of novel therapy for cancer, diabetes and cardiovascular diseases.

Nerve growth factor (NGF) is protein discovered by Rita Levi Montalcini in the 1950s. It plays a crucial role in the development of nervous system. NGF may be produced by a variety of cells even beyond nervous system. NGF modulate cell metabolism by binding to p75NTR and TrkA receptors. NGF is involved in psychological processes and may be the possible therapeutical agent for diabetes, cancer and cardiovascular diseases, which will be described in the article.