Stromal reaction and prognosis in acinic cell carcinoma of the salivary gland

Introduction. Primary acinic cell carcinoma (ACC) is an uncommon malignant neoplasm of the salivary gland (SG), which usually presents as slow growing tumor. Case report. We reported a 69-year-old woman with tumor in the right parotid gland with a 5-year progress. Biopsy sections revealed a hybrid form of ACC with a low- and high-grade component and prominent lymphoid tissue in tumor stroma. Immunohistochemistry was performed to define the molecular profile of this unusual ACC, with special interest for stromal influence on to the proliferative activity of ACC with dedifferentiation. We detected that the level and the type of stromal lymphoid reaction (particularly CD8+/CD4+ ratio) had a significant influence on to Ki-67 index in the high-grade component of ACC, as well as the involvement of the CXCR4 signaling axis in the stromal reaction influence. Conclusion. We suggest that tumor stroma may be a source of potential new tumor biomarkers which can determine the aggressivity of this tumor.[Projekat Ministarstva nauke Republike Srbije, br. 175092

Površinski epitel jajnika hipotireoidnih novorođenih i neonatalnih pacova - iz perspektive PCNA i kaspaze-3

Introduction. The ovarian surface epithelium (OSE) undergoes intensive regeneration and remodelling after each ovulation during the whole reproductive period. This process increases the risk of one of the most common ovarian tumors in women and the female dog. Considering the fact that maternal hypothyroidism highly impacts cell proliferation and cell death during folliculogenesis in the early neonatal period, we aimed to analyze its effect on OSE morphology and dynamics. Materials and Methods. The study was performed on newborn (24-h-old) and neonatal (4-day-old) female rats, a randomized trial between the control and hypothyroid groups, born under controlled circumstances and hypothyroid mothers, respectively. Their ovaries were analyzed histologically and processed to determine the OSE cell height as an average value of four measurement points. Also, the immunopositivity of the proliferating cell nuclear antigen (PCNA) and caspase-3 were assessed semiquantitatively. Results and Conclusions. No major structural differences of OSE were found between groups within the given ages except for a slight increment of OSE cell height and incompleteness of apical cell membrane with cytoplasmic projections in hypothyroid animals. PCNA immunopositivity of the OSE cells was higher in ovaries of hypothyroid animals of both ages in comparison to the controls. Moreover, only scarce OSE cells were caspase-3 positive in both groups and ages, with no difference in immunopositivity. Our study confirms the impact of hypothyroidism in the early postnatal period on morphology and proliferation rate of OSE cells, with no effect on caspase-3 dependent cell removal, which may serve as a premise for future investigation of potential carcinogenesis, in terms of prevention and treatment of ovarian cancer.Uvod. Tokom reproduktivnog perioda, nakon svake ovulacije, površinski epitel (PE) jajnika se intenzivno regeneriše i remodelira. Ovaj proces povećava rizik od nastajanja jednog od najčešćih tumora jajnika kod žena i kuja. Imajući u vidu činjenicu da hipotireoidizam majki u velikoj meri utiče na proliferaciju i ćelijsku smrt u toku folikulogeneze u ranom postnatalnom periodu, cilj rada je bio da analiziramo efekat hipotireoidizma majki na morfologiju i dinamiku PE jajnika potomaka. Materijal i metode. U eksperimentu su korišćeni tek rođeni (24 časa stari) i neonatalni (4 dana stari) mladunci koji potiču od kontrolnih i hipotireoidnih majki. Morfometrijskom analizom određivana je prosečna visina ćelija PE, izmerena na četiri mesta na svakom ispitivanom preseku jajnika. Takođe, imunopozitivnost proliferativnivnog ćelijskog nuklearnog antigena (PCNA) i kaspaze 3 je određivana semikvantitativno. Rezultati i zaključci. Veće promene u strukturi PE jajnika nisu zapažene između grupa, osim blagog povećanja visine ćelija i nepotpune apikalne membrane sa projekcijama citoplazme kod hipotireoidnih životinja. Imunopozitivnost PCNA je značajno povećana u jajnicima hipotireoidnih životinja obe starosne grupe u odnosu na kontrole, dok je imunopozitivnost na kaspazu 3 slabo izražena kod svih životinja. Naše istraživanje je pokazalo da hipotireoidizam u ranom postnatalnom periodu dovodi do promena u morfologiji i proliferaciji ćelija PE, bez efekta na uklanjanje ćelija delovanjem kaspaze 3. Ovaj model može da posluži u budućim istraživanjima potencijalne karcinogeneze u cilju prevencije i tretmana kancera jajnika

Interactions of ruthenium(II)-cymene complexes with cytochrome c

The ruthenium-based antitumour compounds act more via protein targets involved in carcinogenesis, in contrast to platinum-based compounds. Also, after intravenous administration of antitumour complexes proteins are the first binding targets in circulation. Therefore, interactions of anticancer compounds with proteins are important for elucidation of their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes (C1, C2, C3 and C4), developed earlier and with promising cytotoxic activity, are investigated for their interactions with cytochrome c (Cyt). Complexes were incubated with Cyt for 48 h at 37 °C and high-resolution LTQ-Orbitrap ESI MS was used to monitor the formed adducts. The changes in heme state and tertiary structure around the heme were monitored by CD and UV-VIS spectra in the presence of oxygen. The complexes containing two chloride ligands (C2 and C3) were more reactive toward Cyt than those with only one (C1 and C4). The complex with S,N-chelating ligand (C4) was less reactive than one with O,N-chelating ligand (C1). All complexes reduced heme iron of Cyt, but the extent of reduction was inverse to the order of their reactivity to Cyt (C1>C4>>C2>C3). CD spectra in Soret region indicated that Cyt reduction was accompanied with slight tertiary structure change, the rupture of ferro-Met-80 and occupation of this heme coordination site by His-33/His-26. Extent of heme reduction by complexes inverse with respect to their reactivity implies that initially noncovalent binding of complexes occures, causing heme reduction, followed by comlex coordination to protein. In the presence of less reactive complexes more intensive reduction of heme leaves less available histidine residues (main targets for Ru coordination), leading to less efficient formation of adducts

Lysozyme and Cytochrome C adducts of ruthenium(II)-cymene complexes

Objective. In contrast to platinum-based antitumour compounds, the mode of action of ruthenium-based compounds is via protein targets involved in cellular signaling pathways and the histone proteins. As proteins are the first potential binding targets for the complexes in the bloodstream after their intravenous administration, interactions of anticancer therapeutics with proteins are very important to be investigated with aim to elucidate their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes, developed earlier and with promising cytotoxic activity, are investigated for their interactions with proteins, cytochrome c and lysozyme. Material and Methods. Ruthenium(II)-cymene complexes were incubated for 24 and 48 h at 37 °C in the presence of cytochrome c and lysozyme, both in 20 mM ammonium hydrogen carbonate pH 7.4 and water. High-resolution LTQ-Orbitrap ESI MS was used to monitor the adducts formed between ruthenium complexes and proteins. Results. The complexes with two Cl- ligands have shown higher reactivity to proteins than those with only one, and were more reactive toward cytochrome c in comparison to lysozyme. The complex with S,N-chelating ligand was less reactive to proteins than one with O,N-chelating ligand. Species initially coordinating the proteins are most likely dehalogenated complexes. During the time, vivid ligand exchange of non-arene organic ligand L with CO32- and OH- takes place after initial formation of protein adducts. In water, only dehalogenated adducts were identified suggesting that in vivo, in the presence of various anions, dynamic ligand exchange could be expected generating different intermediate protein species. Conclusions. Protein reactivity toward Ru(II) complexes is determined by protein structure and ligands in Ru(II) coordination sphere, but this reactivity should be described from both kinetics, as well as stability aspect. In extracellular or intracellular milieu, ability of metal binding ligands (such as carbonate ions) to bind and to leave, determinate both the extent and mechanism of the binding of ruthenium complexes to the target biomacromolecules for cancer therapy

A NUMERICAL AND EXPERIMENTAL ANALYSIS OF THE DYNAMIC STABILITY OF HYDRAULIC EXCAVATORS

The paper presents the results of a numerical and experimental analysis of the dynamic stability of hydraulic excavators. The analysis has employed the software developed on the basis of a defined general dynamic mathematical model of an excavator grounded in Newton-Euler equations as well as the measured quantities of the excavator operating state in exploitation conditions. The defined model is used to model the members of the excavator kinematic chain using rigid bodies while the actuators (hydraulic cylinders and hydraulic motors) of the excavator drive mechanisms are modeled with elastically dampened elements. The elastically dampened characteristics of the actuators are defined with regard to the size of the actuator as well as to the compressibility and temperature of the hydraulic oil used in the excavator hydrostatic drive system. To illustrate the analysis, the paper provides the results of the analysis of the dynamic stability of a 16000 kg tracked excavator equipped with a manipulator digging bucket of 0.6 m3 in capacity

The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol

We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat