A 2000 patient retrospective assessment of a new strategy for burn wound management in view of infection prevention and treatment

Infections in burn patients are still the principal cause of complications in burn injuries. The aim of this study is to assess a new strategy for burn wound management in view of infection prevention and treatment in the experience of the Burn Treatment Center in Siemianowice Śląskie. The applied methodology involved the analysis of patient records describing the hospital''s epidemiological situation between 2014 and 2016. The analysis also included the use and cost of antibiotics, silver‐containing dressings, and other antiseptics relative to the number of sepsis cases, including those caused by Pseudomonas aeruginosa, as well as the mortality ratio. The total costs of prevention and treatment of infections were reduced, while the use of silver‐containing dressings and antiseptics increased. The number of patients with sepsis decreased, including cases caused by P. aeruginosa, and the mortality ratio was reduced. Introducing a strategy for burn wound‐oriented infection prevention and treatment in burn patients provides a number of benefits. It is also cost‐effective. Using locally applied active dressings and antiseptics can be a welcome choice for often‐unnecessary antibiotic therapy of a suspected or existing burn wound infection.     

Elevated Numbers of Circulating Very Small Embryonic-Like Stem Cells (VSELs) and Intermediate CD14++CD16+ Monocytes in IgA Nephropathy

IgA nephropathy (IgAN) is recognized as most frequent form of primary glomerulonephritis worldwide. IgAN is associated with renal degradation occurring due to irreversible pathological changes leading to glomerulosclerosis and interstitial fibrosis. It remains poorly understood whether and to what extent these changes are followed by the activation of regenerative mechanisms. Therefore, in this study we aimed to evaluate regenerative potential of IgAN patients by quantitating the frequencies of several stem cell types, namely circulating very small embryonic-like stem cells (VSELs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs) as well as different monocyte subsets with varying maturation and angiopoietic potential. Moreover, we analyzed whether changes in stem cell and monocyte frequencies were related to alterations of several chemotactic factors (stromal derived-factor (SDF-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)) and a marker of monocyte/macrophage activation, namely soluble form of CD163 receptor (sCD163). We showed that IgAN patients presented with enhanced levels of VSELs, but not other stem cell types. We also demonstrated significantly elevated numbers of intermediate monocytes known for their M2-like properties as well as high angiopoietic potential and CD163 expression. This finding was accompanied by detection of elevated sCD163 plasma levels in IgAN patients. Taking together, we demonstrated here that IgAN is associated with selective mobilization of VSELs and increased maturation of monocytes towards M2-like and angiopoietic phenotype. These findings contribute to better understanding of the role of regenerative mechanisms in the pathogenesis of chronic inflammation in the course of IgAN.     

An In Vitro Study of the Neurotoxic Effects of <Emphasis Type="Italic">N</Emphasis>-Benzylpiperazine: A Designer Drug of Abuse

Recently, the number of new psychoactive substances has significantly increased. Despite the systematic introduction of prohibition in trade of medicinal products which mimic the effects of illegal drugs, the problem concerning this group of drugs is still important although knowledge about the mechanism of action of those types of substances is scarce. This study aimed to follow the neurotoxic effect of N-benzylpiperazine (BZP), the central nervous system psychostimulant, using the human cancer LN-18 cell model. The statistically significant elevation of LDH levels, increased mitochondrial membrane potential, decreased ATP and increased ROS production, increased levels of DNA damage marker (8-OHdG) and activation of caspases: -3 and -9 confirmed by Real-Time PCR imply the activation of mitochondrial proapoptotic pathways induced by BZP after 24 h incubation. This study is a novel, preliminary attempt to explain the toxicity of one of the most popular designer drug of abuse at the cellular level.     

Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular Tissue

Objective: Tetrahydrobiopterin (BH4) is the essential cofactor of endothelial nitric oxide synthase (eNOS) and intracellular levels of BH4 is regulated by oxidative stress. The aim of this paper was to describe the influence of exogenous endothelin-1 on intracellular BH4 and its oxidation products dihydrobiopterin (BH2) and biopterin (B) in a wide range of vascular tissue.

Design: Segments of internal mammary artery (IMA) and human saphenous vein (SV) from 41 patients undergoing elective surgery were incubated in ET-1 (0.1?μM). Aorta and lung from transgenic mice overexpressing ET-1 in the endothelium (ET-TG) were analysed with regards to intracellular biopterin levels. Human umbilical vein endothelial cells (HUVEC) were incubated in ET-1 (0.1?μM) and intracellular biopterin levels were analysed. From 6 healthy women undergoing caesarean section, subcutaneous fat was harvested and the resistance arteries in these biopsies were tested for ET-mediated endothelial dysfunction.

Results: In HUVEC, exogenous ET-1 (0.1?μM) did not significantly change intracellular BH4, 1.54?±?1.7 vs 1.68?±?1.8?pmol/mg protein; p?=?.8. In IMA and SV, exogenous ET-1(0.1?μM) did not change intracellular BH4 n?=?10, p?=?.4. In aorta from wild type vs ET-TG mice there was no significant difference in intracellular BH4 between the groups: 1.3?±?0.49 vs 1.23?±?0.3?pmol/mg protein; p?=?.6. In resistance arteries (n?=?6) BH4 together with DTE (an antioxidant) was not able to prevent ET-mediated endothelial dysfunction.

Conclusion: ET-1 did not significantly alter intracellular tetrahydrobiopterin levels in IMA, SV, HUVEC or aorta from ET-TG mice. These findings are important for future research in ET-1 mediated superoxide production and endothelial dysfunction.     

Design, synthesis and cytotoxicity of a new series of isoxazolidine based nucleoside analogues

5‐Arylisoxazolidin‐3‐yl‐3‐diethoxyphosphonates have been synthesized from N‐methyl‐C‐diethoxyphosphorylnitrone and vinyl aryls in good yields and their transformation into the respective phosphonic acids has been accomplished via dealkylation procedure using trimethylsilyl bromide. Phosphonates having 1‐ and 2‐naphthyl substituents at C5 in the isoxazolidine ring as well as the respective phosphonic acids have been found cytotoxic to HeLa and K562 cells with IC₅₀ in the 0.1–0.3 mM range. Preliminary studies on mechanism of action imply that intercalation to DNA is not responsible for their cytotoxic properties.     

Two-tier hydrogel degradation to boost endothelial cell morphogenesis

Cell-responsive degradation of biofunctional scaffold materials is required in many tissue engineering strategies and commonly achieved by the incorporation of protease-sensitive oligopeptide units. In extension of this approach, we combined protease-sensitive and -insensitive cleavage sites for the far-reaching control over degradation rates of starPEG-heparin hydrogel networks with orthogonally modulated elasticity, RGD presentation and VEGF delivery. Enzymatic cleavage was massively accelerated when the accessibility of the gels for proteases was increased through non-enzymatic cleavage of ester bonds. The impact of gel susceptibility to degradation was explored for the 3-dimensional ingrowth of human endothelial cells. Gels with accelerated degradation and VEGF release resulted in strongly enhanced endothelial cell invasion in vitro as well as blood vessel density in the chicken chorioallantoic membrane assay in vivo. Thus, combination of protease-sensitive and -insensitive cleavage sites can amplify the degradation of bioresponsive gel materials in ways that boost endothelial cell morphogenesis.     

The multidrug transporter P-glycoprotein in pharmacoresistance to antiepileptic drugs

This review provides an overview of the knowledge on P-glycoprotein (P-gp) and its role as a membrane transporter in drug resistance in epilepsy and drug interactions. Overexpression of P-gp, encoded by the ABCB1 gene, is involved in resistance to antiepileptic drugs (AEDs), limits gastrointestinal absorption and brain access of AEDs. Although several association studies on ABCB1 gene with drug disposition and disease susceptibility are completed to date, the data remain unclear and incongruous. Although the literature describes other multidrug resistance transporters, P-gp is the main extensively studied drug efflux transporter in epilepsy.     

Observation of a new pattern in serogroup-related PCR typing of Listeria monocytogenes 4b isolates

Molecular serogroup-related PCR typing has made the determination of serotypes of Listeria monocytogenes isolates easy and rapid. Amplification of selected lineage- and serotype-related genes can produce serotype patterns reflecting the four major serotypes, 1/2a, 1/2b, 1/2c, and 4b. We found that four isolates in our routine testing had a pattern with the four bands lmo0737, ORF2110, ORF2819, and prs positive, a pattern which has not been previously reported in the literature. After testing with a lineage-specific PCR, hybridization, and conventional agglutination serotyping, the isolates with the new pattern were considered to be serotype 4b.