Opposite effects of two zinc(II) dithiocarbamates on NF-kB pathway

Inhibiting nuclear factor-kappaB (NF-kB) activation in anticancer and antiinflammatory therapy is of topical interest. Current research in molecular biology has dramatically advanced in the understanding of the cellular events involved in NF-kB induction. Dithiocarbamates, in particular diethyldithiocarbamate and pyrrolidinedithiocarbamate, have been known and widely used as strong inhibitors of NF-kB signaling pathway for more than ten years. Their activity is frequently thought to be due to chelating of zinc or copper present in serum supplemented in the culture medium. Zinc(II) diethyldithiocarbamate (Et2Zn) and zinc(II) dibenzyldithiocarbamate (Bz2Zn) were prepared by direct synthesis in aqueous millieu. They were structurally characterized by X-ray analysis (solid phase) and mass spectrometry (aqueous conditions). Et2Zn and Bz2Zn both in 20 micromolar concentration were applied to HeLa cells. The status of NF-kB signaling was assessed as nuclear translocation of p65 subunit. Surprisingly, Et2Zn activated NF-kB pathway, while TNF-dependent activation of NF-kB was inhibited by Bz2Zn. Our results are preliminary

Influence of Hydrogencalcium Salts of Oxidized Cellulose on MMP-2, MMP-9 and TNF-α Production and Wound Healing in Non-Healing Wounds

Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tumour necrosis factor-α (TNF-α) may influence wound healing in non-healing wounds and wound closure. The aim of the study was to test the hypothesis that the hydrogencalcium salts of oxidised cellulose change the production of matrix metalloproteinase (MMPs) and TNF-α, wound size and number of bacterial strains in non-healing wounds. We analyzed MMP-2, MMP-9 and TNF-α in the wound fluid from 20 patients by ELISA every fourteens days over six weeks. Wound size, pain, wound closure and bacterial strains in the wound were also investigated. The wound size was reduced at 14 patients and pain in 16 patients. Bacterial contamination of the wound was significantly decreased after treatment. The level of MMP-2 correlated with TNF-α production. The level of MMP-9 was unchanged during the healing period. We concluded that the hydrogencalcium salts of oxidised cellulose have positive effect on reduction of bacterial contamination, wound size and pain.</p

Influence of Hydrogencalcium Salts of Oxidized Cellulose on MMP-2, MMP-9 and TNF-α Production and Wound Healing in Non-Healing Wounds

Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tumour necrosis factor-α (TNF-α) may influence wound healing in non-healing wounds and wound closure. The aim of the study was to test the hypothesis that the hydrogencalcium salts of oxidised cellulose change the production of matrix metalloproteinase (MMPs) and TNF-α, wound size and number of bacterial strains in non-healing wounds. We analyzed MMP-2, MMP-9 and TNF-α in the wound fluid from 20 patients by ELISA every fourteens days over six weeks. Wound size, pain, wound closure and bacterial strains in the wound were also investigated. The wound size was reduced at 14 patients and pain in 16 patients. Bacterial contamination of the wound was significantly decreased after treatment. The level of MMP-2 correlated with TNF-α production. The level of MMP-9 was unchanged during the healing period. We concluded that the hydrogencalcium salts of oxidised cellulose have positive effect on reduction of bacterial contamination, wound size and pain.</p

A Randomized Comparison of Non-Channeled GlidescopeTM Titanium Versus Channeled KingVisionTM Videolaryngoscope for Orotracheal Intubation in Obese Patients with BMI &gt; 35 kg·m−2

Videolaryngoscopes may improve intubating conditions in obese patients. A total of 110 patients with a body mass index &gt; 35 kg∙m&minus;2 were prospectively randomized to tracheal intubation using non-channeled Glidescope Titanium or channeled King Vision videolaryngoscope. The primary outcome was the time to tracheal intubation. Secondary outcomes included: total success rate, number of attempts, the quality of visualization, peri-procedural and post-proceduralcomplications. Time to the first effective breath was shorter with the King Vision (median; 95% CI)&mdash;36; 34&ndash;39 s vs. 42; 40&ndash;50 in the Glidescope group (p = 0.007). The total success rate was higher in the Glidescope group&mdash;100% vs. 89.1% (p = 0.03). There was a higher incidence of moderate and difficult laryngoscopy in the King Vision group. No difference was recorded in first attempt success rates, total number of attempts, use of additional maneuvers, intraoperative trauma, or any significant decrease in SpO2 during intubation. No serious complications were noted and the incidence of postoperative complaints was without difference. Although tracheal intubation with King Vision showed shorter time to the first breath, total success was higher in the Glidescope group, and all but one patients where intubation failed with the KingVision were subsequently intubated with the Glidescope

Electrocatalytic Assay for Monitoring Methylglyoxal-Mediated Protein Glycation

Protein glycation is a complex process that plays an important role in diabetes mellitus, aging, and the regulation of protein function in general. As a result, current methodological research on proteins is focused on the development of novel approaches for investigating glycation and the possibility of monitoring its modulation and selective inhibition. In this paper, a first sensing strategy for protein glycation is proposed, based on protein electroactivity measurement. Concretely, the label-free method proposed is based on the application of a constant-current chronopotentiometric stripping (CPS) analysis at Hg-containing electrodes. The glycation process was monitored as the decrease in the electrocatalytic protein signal, peak H, observed at highly negative potentials at around −1.8 V (vs Ag/AgCl_3 M KCl), which was previously ascribed to a catalytic hydrogen evolution reaction (CHER). Using this method, a model protein bovine serum albumin was investigated over 3 days of incubation with the glycation agent methylglyoxal in the absence or presence of the glycation inhibitor aminoguanidine (pimagedine). The electrochemical methodology presented here could open up new possibilities in research on protein glycation and oxidative modification. The methodology developed also provides a new option for the analysis of protein intermolecular interactions using electrochemical sensors, which was demonstrated by the application of a silver solid amalgam electrode (AgSAE) for monitoring the glycation process in samples of bovine serum albumin, human serum albumin, and lysozyme

Succinobucol's New Coat - Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis), and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-yl)phenyl]sulfanyl}ethyl)sulfanyl]phenoxy}-4-oxo-butanoic acid]) possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol) possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.peerReviewe