Peritonitis-induced antitumor activity of peritoneal macrophages from uremic patients.

The macrophages belong to the effector cells of both nonspecific and specific immune response. These cells generally express little cytotoxicity unless activated. The present work was intended to determine if peritoneal macrophages collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) during episodes of peritonitis were active against human tumor cell lines without further in vitro stimulation. We also compared macrophage antitumor potential with effectiveness of drugs used in cancer therapy (taxol and suramin). Conditioned medium (CM) of macrophages collected during inflammation-free periods did not exhibit cytostatic and cytotoxic activity against both tumor (A549 and HTB44) and non-transformed (BEAS-2B and CRL2190) cells. Exposure of tumor cells to CM of macrophages harvested during peritonitis resulted in significant suppression of proliferation, impairment of viability and induction of apoptosis, in contrast to non-transformed cells, which remained unaffected. The efficacy of CM of inflammatory macrophages as an antitumor agent appeared to be comparable to cytostatic and cytotoxic potency of taxol and suramin or, in the case of HTB44 cells, even higher. The results obtained suggest that activated human macrophages might represent a useful tool for cancer immunotherapy

Peritonitis-induced antitumor activity of peritoneal macrophages from uremic patients

The macrophages belong to the effector cells of both nonspecific and specific immune response. These cells generally express little cytotoxicity unless activated. The present work was intended to determine if peritoneal macrophages collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) during episodes of peritonitis were active against human tumor cell lines without further in vitro stimulation. We also compared macrophage antitumor potential with effectiveness of drugs used in cancer therapy (taxol and suramin). Conditioned medium (CM) of macrophages collected during inflammation-free periods did not exhibit cytostatic and cytotoxic activity against both tumor (A549 and HTB44) and non-transformed (BEAS-2B and CRL2190) cells. Exposure of tumor cells to CM of macrophages harvested during peritonitis resulted in significant suppression of proliferation, impairment of viability and induction of apoptosis, in contrast to non-transformed cells, which remained unaffected. The efficacy of CM of inflammatory macrophages as an antitumor agent appeared to be comparable to cytostatic and cytotoxic potency of taxol and suramin or, in the case of HTB44 cells, even higher. The results obtained suggest that activated human macrophages might represent a useful tool for cancer immunotherapy

The effect of hemodynamically-guided hypotensive therapy in one-year observation: Randomized, prospective and controlled trial (FINEPATH study)

Background: The use of impedance cardiography (ICG) revealed to provide beneficial blood pressure (BP) lowering effect. However, the follow-up in previous trials was short and brachial BP was the only evaluated hemodynamic variable. Thus, we aimed to estimate the influence of ICG-guided therapy on brachial and central BP, impedance-derived hemodynamic profile and echocardiographic features after 12 months in a randomized, prospective and controlled trial (NCT01996085). Methods: One hundred and forty-four hypertensives were randomly assigned to groups of empiric (GE) and ICG-guided therapy (HD). Office BP, ambulatory BP monitoring, central BP and echocardiography (left ventricular hypertrophy and diastolic function assessment) were performed before and after 12 months of treatment. Results: Blood pressure reduction was higher in HD (office BP: 21.8/14.1 vs. 19.9/11.8 mm Hg; mean 24-h BP: 19.0/10.9 vs. 14.4/9.2 mm Hg). However, the only statistically significant differences were: percentage of patients achieving BP reduction of minimum 20 mm Hg for of­fice diastolic BP (27.3% vs. 12.1%; p = 0.034) and mean 24-h systolic BP (49.1% vs. 27.3%; p = 0.013). More pronounced improvement in the left ventricular diastolic dysfunction (delta E/A 0.34 vs. 0.12, p = 0.017) was the only other beneficial hemodynamic effect. Conclusions: Beneficial BP lowering effect of hemodynamically-guided pharmacotherapy, observed previously in short-term observation, persists over time. Hemodynamic effects of such a treatment approach, especially those of prognostic value (central BP, myocardial hypertrophy), should be evaluated in further studies including patients with resistant hypertension, heart failure, diabetes mellitus and chronic kidney disease

Molecular profiling of the intestinal mucosa and immune cells of the colon by multi-parametric histological techniques

The impact of the post-mortem interval (PMI) on the optical molecular characteristics of the colonic mucosa and the gut-associated lymphoid tissue (GALT) were examined by multi-parametric measurements techniques. Inflammatory cells were identified by immunohistochemical staining. Molecular parameters were estimated using the Raman spectroscopy (RS) and Fourier Transform Infrared (FTIR) spectroscopic imaging. The 3D refractive index (3D-RI) distributions of samples were determined using the digital holographic tomography. The distribution of immune cells between post-mortem (PM) and normal controls did show significant differences for CD4 (P = 0.0016) or CD8 (P < 0.0001), whose expression level was decreased in PM cases. No association was found between individual PMI values and inflammatory cell distribution. However, there was a tendency for a negative correlation between CD4(+) cells and PMI (r = − 0.542, P = 0.032). The alterations ongoing in post-mortem tissue may suggest that PMI has a suppressive effect on the effector properties of the cell-mediated immunity. Moreover, it was confirmed that spectroscopic and digital holotomographic histology are also a useful technique for characterization of the differences in inflammation of varying intensity and in GALT imaging in a solid tissue. Anatomical location of immune cells and methods of tissue fixation determine the molecular and optical parameters of the examined cases

Risk of left atrial appendage thrombus in patients with atrial fibrillation and chronic kidney disease

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with an increased risk of ischemic stroke. The aim of this study was to compare the clinical characteristics, the incidence of left atrial appendage (LAA) thrombus and its predictors, and spontaneous echo contrast (SEC) in a population of patients with AF depending on estimated glomerular filtration rate (eGFR) values. Methods: This study included 1962 patients who underwent transesophageal echocardiographic examination (TEE) prior to cardioversion or ablation in the years 2014–2018 in three cardiac centers. Results: More than a quarter of AF patients had decreased eGFR ( &lt; 60 mL/min/1.73 m2) and were characterized as a high-risk population, with more comorbidities, higher thromboembolic and bleeding risk compared to those with normal renal function. Oral anticoagulation (OAC) was prescribed in 97% and 93% of patients with decreased and normal eGFR, respectively, with a higher prevalence of prescribed non-vitamin K antagonist oral anticoagulants (NOACs). The incidence of LAA thrombus (24%, 9% and 4%) and SEC (25%, 25% and 19%) increases simultaneously with a decrease in eGFR ( &lt; 30, 30–59 and &gt; 60 mL/min/1.73 m2, respectively). Among patients prescribed reduced doses of NOAC, those with decreased eGFR were more often observed with LAA thrombus (10% vs. 2.5%). Non-paroxysmal AF, heart failure and previous bleeding were predictors of LAA thrombus, irrespective of eGFR value. CKD was the predictor of LAA thrombus in all patients including those with non-paroxysmal AF, males, without diabetes, without hypertension and with CHA2DS2-VASc &lt; 2. Conclusions: Despite OAC, patients with concomitant AF and CKD remain at high risk for LAA thrombus formation

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 x 10(-5) were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 x 10(-8)) were characterized by in silica functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 x 10(-8); odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 x 10(-8), OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silica studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.Peer reviewe

The influence of the terrain surface on the spreading of pollutants based on the example of selected heavy metals

W celu określenia występowania i wpływu bariery górskiej na ekspansję zanieczyszczeń oraz ustalenia stopnia skażenia gleb wybranymi metalami ciężkimi przeprowadzono analizę zawartości kadmu, cynku i ołowiu w glebach na terenie Gorców. Do pomiarów wykorzystano absorpcyjną spektrometrię atomową. Średnia zawartość wyniosła kolejno: dla ołowiu - 23,64±0,04 mg/kg, kadmu - 0,61±0,01 mg/kg, cynku - 73,00±0,04 mg/kg. Zawartości metali nie przekroczyły norm określonych w polskim ustawodawstwie. Zaobserwowano różnice w stężeniach metali ciężkich po stronie dowietrznej i zawietrznej. Badania wykazały że, bariera górska hamuje rozprzestrzenianie się zanieczyszczeń pyłowych. Jednak jej wpływ nie jest wyraźny.In order to determine the occurrence and impact of the mountain barrier on the expansion of pollutants and determine the degree of soil contamination with selected heavy metals, the analysis of the content of cadmium, zinc and lead in soils in the Gorce area was carried out. Atomic absorption spectrometry was used for measurements. The average content of heavy metals was follows: lead –23,64 ± 0,04 mg/kg, cadmium –0,61 ± 0,01 mg/kg, zinc –73,00 ± 0,04 mg/kg. The metals’ concentration did not exceed the standards defined in Polish legislation. Differences between heavy metals’ concentrations on the windward and leeward side were observed. The studies have shown that the mountain barrier inhibits the spread of particulates pollutions. However, its impact is not clear, as the local sources of pollution have to be taken in consideration too

Lead extraction from soil using selected chelating reagents

Gleba to wierzchnia warstwa skorupy ziemskiej, stanowiąca źródło wody i składników odżywczych dla roślin jak również, środowisko życia dla wielu organizmów. Szybki rozwój różnych dziedzin gospodarki, głównie przemysłu oraz transportu, obserwowany na przestrzeni kilkudziesięciu ostatnich lat spowodował spore zanieczyszczenia tego elementu środowiska między innymi metalami ciężkimi, w tym ołowiem. Pierwiastek ten jest dla organizmów toksyczny i charakteryzuje się niską mobilnością w glebie. W części literaturowej niniejszej pracy przedstawiono definicję metalu ciężkiego, formy, w jakich metale występują w glebie. Omówiono wpływ ołowiu na funkcjonowanie roślin i ludzi. Scharakteryzowano także glebę, jej właściwości oraz funkcję. Poruszono problem degradacji gleb, jak również przedstawiono metody remediacji gruntów. Przedstawiono także krótkie charakterystyki wykorzystanych odczynników chelatujących: soli sodowej kwasu etylenodiaminotetraoctowego (EDTA), kwasu cytrynowego oraz soli sodowej kwasu S,S- etylenoddiamino-N,N’ – dibursztynowego (EDDS).Najważniejszą częścią badań było określenie wydajności ekstrakcji ołowiu z gleb sztucznie skażonych, z wykorzystaniem wybranych chelatorów oraz optymalizacja czasu wymywania ołowiu z gleb. Całkowitą zawartość ołowiu w próbkach piasku, gliny i lessu oraz stężenie ołowiu w roztworach po ekstrakcji określono za pomocą płomieniowej atomowej spektrometrii absorpcyjnej. Próbki przygotowano do analizy wykorzystując mineralizację ciśnieniową wspomaganą energią mikrofal. Analizę sekwencyjną BCR oraz analizę sekwencyjną wg Tessiera wykorzystano, aby określić stężenie ołowiu w poszczególnych formach. Oprócz badań mających na celu określnie właściwości chemicznych przeprowadzono również podstawowe analizy gleboznawcze (pomiar pH, pomiar zawartości węgla organicznego, analizę granulometryczną oraz pomiar zawartości frakcji spławialnej), dzięki którym zakwalifikowano gleby to odpowiednich podgrup granulometrycznych. Naturalnie ołów występuje głównie w glebach w formie rezydualnej. Zawartość w formie jonowymiennej i węglanowej nie przekracza 10%. W glebach sztucznie wzbogaconych w ten pierwiastek zaobserwowano wzrost zawartości tego metalu w formach: jonowymiennej i węglanowej, tlenkowej i organicznej. Przeprowadzone badania pokazały, że zarówno EDDS i EDTA usuwają ołów z piasku i gliny z około 100% wydajnością. Wydajność ta spada do około 80% dla gleby lessowej. Kwas cytrynowy zdecydowanie gorzej wiąże ołów. Wydajności ekstrakcji w tym przypadku są około pięciokrotnie niższe w stosunku do pozostałych chelatorów. Otrzymane wyniki pokazują że optymalny czas prowadzenia reakcji to około 30 min.The main goal of the master thesis was the determination of the extraction efficiency of lead from contaminated soils using selected chelating reagents such as EDTA, EDDS and citric acid. The next purpose of research was optimization time for removal of lead from soils and comparison the effectiveness of extractants used.Atomic absorption spectrometry was used for measurements of total concentration of lead and concentration after leaching process. The samples were prepared for analysis with use the microwave mineralization technique and BCR sequential extraction method.The results showed that solution of sodium ethylendiaminetetraacetic acid and solution of sodium salt of S,S-ethylenediamine-N,N’-disuccinic acid have the best efficiency of removal lead from soil. The efficiency of chelating for citric acid was very confined. The results also depended on the granulometic composition of soil. In the case of loess performance was lower than in sandy soil and clay. The optimal time of chelating was approximately 30 minutes