Dziecko z asplenią w praktyce lekarza pierwszego kontaktu

Przedstawiono rolę lekarza pierwszego kontaktu jako niezwykle istotnego ogniwa w realizacji programu kompleksowej opieki nad dzieckiem z asplenią. Opisano postępowanie, które obejmuje realizację profilaktyki przeciwinfekcyjnej w postaci szczepień ochronnych oraz długotrwałej antybiotykoterapii, postępowanie w nadpłytkowości po splenektomii oraz szeroko rozumianą edukację pacjenta i jego rodziny. W pracy zamieszczono przykłady pięciu sytuacji klinicznych, z jakimi może spotkać się lekarz pierwszego kontaktu mający pod swoją opieką dziecko bez śledziony: stosowanie profilaktyki antybiotykowej, leczenie posocznicy, postępowanie w przypadku pogryzienia przez psa i w przypadku nadpłytkowości po splenektomii

Remarks on stone vessels from Islamic layers on Bijan Island

Excavations on Bijan Island in western Iraq were conducted by the Polish Centre of Mediterranean Archaeology, University of Warsaw, in 1979–1983, as part of the international Haditha Dam rescue project. A multi-layered site was uncovered, featuring complex architectural structures and a rich archaeological assemblage. Four main settlement phases were distinguished: Neo-Assyrian, Parthian, Roman and early Islamic. The present paper focuses on stone vessels attesting to extensive use of stone for utility purposes. The assemblage complements knowledge about the inhabitants of early Islamic Bijan and their economic activitie

Failaka Archaeological Research Project. Preliminary results after the first season of excavation at the Kharaib el-Desht site in 2013/ Appendix 1: Kharaib el-Desht 2013: pottery. Preliminary report/ Appendix 2: Survey of Kharaib el-Desht Bay on Failaka Island: preliminary report

The site of Kharaib el-Desht on Failaka Island, Kuwait, was explored by an archaeological Kuwaiti–Polish team for the first time in 2013. The project included a survey and underwater archaeological research. Preliminary results indicate a dating of the site to the late Islamic period. Pottery collected from the survey of the site and from the excavations has been studied in a sepearate appendix to this report. As for the underwater and waterfront archaeology project, the main objective was to locate and describe seashore archaeological sites, provide documentary evidence and manage proper preservation of the discoveries in order to further educational opportunities

4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR)—A Novel Oncometabolite Modulating Cancer-Endothelial Interactions in Breast Cancer Metastasis

The accumulation of specific metabolic intermediates is known to promote cancer progression. We analyzed the role of 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR), a nucleotide metabolite that accumulates in the blood of cancer patients, using the 4T1 murine in vivo breast cancer model, and cultured cancer (4T1) and endothelial cells (ECs) for in vitro studies. In vivo studies demonstrated that 4PYR facilitated lung metastasis without affecting primary tumor growth. In vitro studies demonstrated that 4PYR affected extracellular adenine nucleotide metabolism and the intracellular energy status in ECs, shifting catabolite patterns toward the accumulation of extracellular inosine, and leading to the increased permeability of lung ECs. These changes prevailed over the direct effect of 4PYR on 4T1 cells that reduced their invasive potential through 4PYR-induced modulation of the CD73-adenosine axis. We conclude that 4PYR is an oncometabolite that affects later stages of the metastatic cascade by acting specifically through the regulation of EC permeability and metabolic controls of inflammation

Differences in Extracellular NAD⁺ and NMN Metabolism on the Surface of Vascular Endothelial Cells

The disruption of the metabolism of extracellular NAD+ and NMN may affect related signaling cascades and pathologies, such as cardiovascular or respiratory system diseases. We aimed to study NAD+ and NMN hydrolysis on surface endothelial cells of diverse origins and with genetically modified nucleotide catabolism pathways. We tested lung endothelial cells isolated from C57BL/6 J wild-type (WT) and C57BL/6 J CD73 knockout (CD73 KO) mice, the transfected porcine iliac artery endothelial cell line (PIEC) with the human E5NT gene for CD73 (PIEC CD73), and a mock-transfected control (PIEC MOCK), as well as HMEC-1 and H5V cells. Substrate conversion into the product was followed by high-performance liquid chromatography (HPLC). We showed profound differences in extracellular NAD+ and NMN metabolism related to the vessel origin, species diversity, and type of culture. We also confirmed the involvement of CD38 and CD73 in NAD+ and NMN cleavage

Rosiglitazone Ameliorates Cardiac and Skeletal Muscle Dysfunction by Correction of Energetics in Huntington’s Disease

Huntington’s disease (HD) is a rare neurodegenerative disease that is accompanied by skeletal muscle atrophy and cardiomyopathy. Tissues affected by HD (central nervous system [CNS], skeletal muscle, and heart) are known to suffer from deteriorated cellular energy metabolism that manifests already at presymptomatic stages. This work aimed to test the effects of peroxisome proliferator-activated receptor (PPAR)-γ agonist—rosiglitazone on grip strength and heart function in an experimental HD model—on R6/1 mice and to address the mechanisms. We noted that rosiglitazone treatment lead to improvement of R6/1 mice grip strength and cardiac mechanical function. It was accompanied by an enhancement of the total adenine nucleotides pool, increased glucose oxidation, changes in mitochondrial number (indicated as increased citric synthase activity), and reduction in mitochondrial complex I activity. These metabolic changes were supported by increased total antioxidant status in HD mice injected with rosiglitazone. Correction of energy deficits with rosiglitazone was further indicated by decreased accumulation of nucleotide catabolites in HD mice serum. Thus, rosiglitazone treatment may not only delay neurodegeneration but also may ameliorate cardio- and myopathy linked to HD by improvement of cellular energetics

Table_1_Inhibition of MC38 colon cancer growth by multicomponent chemoimmunotherapy with anti-IL-10R antibodies, HES-MTX nanoconjugate, depends on application of IL-12, IL-15 or IL-18 secreting dendritic cell vaccines.docx

BackgroundThe tumor microenvironment (TME) provides a conducive environment for the growth and survival of tumors. Negative factors present in TME, such as IL-10, may limit the effectiveness of cellular vaccines based on dendritic cells, therefore, it is important to control its effect. The influence of IL-10 on immune cells can be abolished e.g., by using antibodies against the receptor for this cytokine - anti-IL-10R. Furthermore, the anticancer activity of cellular vaccines can be enhanced by modifying them to produce proinflammatory cytokines, such as IL-12, IL-15 or IL-18. Additionally, an immunomodulatory dose of methotrexate and hydroxyethyl starch (HES-MTX) nanoconjugate may stimulate effector immune cells and eliminate regulatory T cells, which should enhance the antitumor action of immunotherapy based on DC vaccines. The main aim of our study was to determine whether the HES-MTX administered before immunotherapy with anti-IL-10R antibodies would change the effect of vaccines based on dendritic cells overproducing IL-12, IL-15, or IL-18.MethodsThe activity of modified DCs was checked in two therapeutic protocols - immunotherapy with the addition of anti-IL10R antibodies and chemoimmunotherapy with HES-MTX and anti-IL10R antibodies. The inhibition of tumor growth and the effectiveness of the therapy in inducing a specific antitumor response were determined by analyzing lymphoid and myeloid cell populations in tumor nodules, and the activity of restimulated splenocytes.Results and conclusionsUsing the HES-MTX nanoconjugate before immunotherapy based on multiple administrations of anti-IL-10R antibodies and cellular vaccines capable of overproducing proinflammatory cytokines IL-12, IL-15 or IL-18 created optimal conditions for the effective action of these vaccines in murine colon carcinoma MC38 model. The applied chemoimmunotherapy caused the highest inhibition of tumor growth in the group receiving DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg at the level of 72.4%. The use of cellular vaccines resulted in cytotoxic activity increase in both immuno- or chemoimmunotherapy. However, the greatest potential was observed both in tumor tissue and splenocytes obtained from mice receiving two- or three-component vaccines in the course of combined application. Thus, the designed treatment schedule may be promising in anticancer therapy.</p