Dynamic Perfusion Computed Tomography for the Assessment of Concomitant Coronary Artery Disease in Patients with a History of Percutaneous Transluminal Angioplasty for Chronic Limb-Threatening Ischemia-A Pilot Study.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is associated with high rates of long-term cardiovascular mortality. Exercise stress testing to detect obstructive coronary artery disease (CAD) can be difficult in this subset of patients due to inability to undergo exercise testing, presence of balanced ischemia and severe coronary artery calcification (CAC). AIM: To test the feasibility of regadenoson stress dynamic perfusion computed tomography (DPCT) in CLTI patients. METHODS: Between 2018 and 2023, coronary computed tomography angiography (CTA) and, in the case of a calcium score higher than 400, DPCT, were performed in 25 CLTI patients with a history of endovascular revascularization. RESULTS: Of the 25 patients, 19 had a calcium score higher than 400, requiring DPCT image acquisition. Obstructive CAD could be ruled out in 10 of the 25 patients. Of the 15 CTA/DPCT+ patients, 13 proceeded to coronary angiography (CAG). Revascularization was necessary in all 13 patients. In these 13 patients, vessel-based sensitivity and specificity of coronary CTA/DPCT as compared to invasive evaluation was 75%, respectively. At follow-up (27 ± 21 months) there was no statistically significant difference in all-cause mortality between CTA/DPCT- positive and -negative patients (p = 0.065). CONCLUSIONS: Despite a high prevalence of severe CAC, coronary CTA complemented by DPCT may be a feasible method to detect obstructive and functionally significant CAD in CLTI patients.

Polarography as a technique of choice for the evaluation of total antioxidant activity: The case study of selected Coprinus Comatus extracts and quinic acid, their antidiabetic ingredient.

This study was focused on in vitro screening of the total antioxidant activity of the selected extracts of the mushroom Coprinus comatus and quinic acid, one of their antidiabetic ingredients, by an uncommon electrochemical assay. Indeed, direct current (DC) polarographic HydroxoPerhydroxo Mercury(II) Complex (HPMC) assay based on decrease of anodic limiting current originating from HPMC formation in alkaline solutions of hydrogen peroxide at potential of mercury dissolution, observed upon gradual addition of antioxidants, was applied herein for the estimation of the natural products' antioxidativity. Quinic acid was found to exhibit most promising antioxidant potential (4.0 ± 0.2%µL-1) being ≈ 2-fold more active than the screened C. comatus extract samples. Actually, such a finding puts some light on the antioxidativity of cyclic polyols, well understimated class of organic compounds, compared to aromatic (poly)phenolics. As a low cost, easy-to handle and accurate this polarographic assay may be thoroughly recommended for much broader use. [Formula: see text].

Detection of myocardial inflammation by 18F-FDG-PET/CT in patients with systemic sclerosis without cardiac symptoms: a pilot study.

OBJECTIVES: Primary cardiac manifestation is a common complication of systemic sclerosis (SSc) with poor prognosis. The aim of the current study was to detect potential myocardial inflammation present in asymptomatic SSc patients by 18F-FDG-PET/CT and to investigate its relationship with early signs of myocardial dysfunction as detected by 2D speckle tracking echocardiography (2DSTE). METHODS: Sixteen consecutive patients with SSc and 9 control patients without clinical evidence of cardiac involvement were enrolled in the study. On 18F-FDG-PET acquired images blood-pool normalised SUV ratio and heterogenity index (HI: standard deviation of SUV divided with mean SUV) were calculated. Within 24 hours all SSc patients underwent 2DSTE strain analysis. RESULTS: Eight of 16 SSc patients were found to be visually PET-positive and showed significantly higher myocardial 18F-FDG SUV ratio (1.78±0.74 vs. 0.98±0.03; p<0.05) and heterogenity index (0.13±0.02 vs. 0.05±0.02; p<0.001) as compared to the control group. FDG-PET/CT derived values did not differ significantly between visually PET-negative (8/16) and control patients (SUV ratio: 0.98±0.05 vs. 0.98±0.03; HI: 0.05±0.01 vs. 0.05±0.02). Global left ventricular longitudinal strain values did not differ significantly between PET-positive and negative patients (17.18±3.49% vs. 17.59±3.65%). CONCLUSIONS: Myocardial inflammation, as a potential sign of early cardiac involvement can be detected by 18-FDG-PET/CT in a considerable percentage of systemic sclerosis patients presenting without cardiac symptoms.

Antioxidant efficiency of polyphenols from coffee and coffee substitutes-electrochemical versus spectrophotometric approach.

Antioxidant (AO) capacity of instant, espresso, filter and Turkish/Greek coffee brews, coffee substitutes (roasted chicory root, barley, pea, chickpea, carob and dried fig) and individual compounds (phenolic acids, flavonoids, methylxanthines, N-methyl pyridinium and HMW melanoidins) was assessed using DC polarographic assay based on decrease of anodic current originating from hydroxo-perhydroxo mercury complex formed in alkaline solutions of H2O2 at potential of mercury dissolution, as well as three spectrophotometric assays (DPPH, ABTS and FRAP). A large difference between applied assays ability to recognize various types of individual AOs was noticed. Only according to DC polarographic assay significant AO activity was ascribed to methylxanthines and N-methyl pyridinum. The total content of phenolics (TPC) present in complex samples was determined by FC assay. The highest TPC was ascribed to instant coffees and coffee substitutes while the lowest to decaffeinated filter coffee. Complex samples were grouped based on principal components analysis, phenolics AO coefficient, calculated as the ratio between AO capacity and TPC, and relative AO capacity index (RACI), calculated by assigning equal weight to all applied assays including FC. The highest values of RACI were ascribed to instant coffee brews, followed by substitutes while the lowest to the decaffeinated espresso coffee.

Evaluation of the genotoxicity of alpha-amanitin in mice bone marrow cells.

Alpha-amanitin is a known cytotoxic substance found in some mushroom species including Amanita phalloides. Its main mechanism of action is to block the transcription, which can lead to cell death. Lack of reports on the genotoxicity of this toxin was an inspiration for undertaking this experiment. Genotoxic effect of α-amanitin on balb/c mice bone marrow cells was tested using: comet assay and chromosomal aberration test. The tested substance was given once by intraperitoneal administration to animals at doses: 0.1 mg/kg, 0.15 mg/kg and 0.25 mg/kg (LD50) body weight with 48 h exposure. The comet assay demonstrated a statistically significant increase in DNA damage for all the investigated α-amanitin doses compared to the negative control (p < 0.0001). The exposure to 0.15 and 0.25 mg/kg doses of α-amanitin also generated a statistically significant increase in the frequency of chromosomal aberrations in bone marrow cells of mice compared to the negative control (p < 0.05). The genotoxic effect induced by α-amanitin in mammalian cells can result in genome instability and its functional consequences.

Electrochemical versus spectrophotometric assessment of antioxidant activity of hop (Humulus lupulus L.) products and individual compounds.

Antioxidant (AO) activity of extracts of hop cones (Serbian domestic varieties) and commercial hop products (Saaz, Spalter, Spalter select, and Magnum pellets) was determined by parallel application of recently developed direct current (DC) polarographic and widely used DPPH assay. Correlations between 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging and total phenolics (TPC) determined by the Folin-Ciocalteu assay (FC) (0.99), and between H2O2 scavenging (HPS) and humulone content (H) determined by conductometric method (0.94), total resins (TR) (0.85), and hop storage index (HIS) (-0.90), were found statistically significant at p < 0.05 level while complete lack of HPS correlation with TPC and DPPH was observed. To obtain an insight into differences between results of AO assays applied, activity of individual compounds, prevalent hop phenolics, and bitter acids was determined. By far superior HPS activity of humulone was followed by catechin, quercetin, xanthohumol, lupulone, and rutin. In contrast, DPPH scavenging activity of phenolics (quercetin > catechin > rutin > xantohumol) was found substantially higher than activity of bitter acids. According to ferric reducing antioxidant power (FRAP) and scavenging of 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), higher AO activity was ascribed to phenolics, while almost neglecting humulone. Besides reliability, low cost, and an easy-to-handle procedure, an ability to recognize humulone as the major contributor of hop AO activity could allow DC polarographic assay to be applied in analysis of various hop-derived products.

Evaluation of micronuclei in mice bone marrow and antioxidant systems in erythrocytes exposed to α-amanitin.

α-Amanitin, the main toxic substance from mushroom species (Amanita genus), blocks the activity of RNA polymerase II (Pol II) in mammalian cells causing inhibition of transcription and subsequent synthesis of structural and enzymatic proteins. It has been postulated that α-amanitin generates the increase of reactive oxygen species (ROS) concentration. The micronucleus (MN) test was used on an animal experimental model to evaluate possible potential genotoxic effect of α-amanitin on mice bone marrow cells. At the same time the activity of antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) as well as concentration of thiobarbituric acid reactive substance (TBARS) were investigated in the lysate of mice erythrocytes. α-Amanitin was administered intraperitoneally at the doses: 0.1, 0.15, and 0.25 mg/kg bw (LD(50) for mice) 48 h prior to sacrification. A statistically significant increase of SOD activity was observed in the hemolysate for all the investigated α-amanitin doses as compared to the negative control (p < 0.05). CAT activity for α-amanitin doses 0.1 and 0.15 mg/kg was higher in comparison to the negative control but the differences were not statistically significant (p > 0.05). However, for the dose 0.25 mg/kg the activity of CAT was statistically significantly higher (p < 0.001). All the tested α-amanitin doses decreased TBARS concentration in the hemolysate as compared to the negative control but the differences were not statistically significant (p > 0.05). A statistically significant increase of mean values of MN percent was found in polychromatic erythrocytes (PCEs) as compared to the negative control for α-amanitin dose 0.1 and 0.25 mg/kg (p < 0.05). For the dose 0.15 mg/kg the mean value of MN percent was higher but it did not demonstrate statistical significance (p > 0.1). The observed disturbances in the activity of the examined antioxidant enzymes in cells exposed in vivo to α-amanitin suggest indirect genotoxic effect of α-amanitin through ROS generation.

Antioxidant capacity of teas and herbal infusions: polarographic assessment.

Hydrogen peroxide scavenging (HPS) activity of unfermented (green, yellow, and white), partially fermented (oolong), and completely fermented (black) tea ( Camellia sinensis ), maté ( Ilex paraguariensis ), and various herbal infusions, as well as individual compounds (flavan-3-ols, flavonols, cinnamic and benzoic acids, and methylxanthines), was assessed by recently developed direct current (DC) polarographic assay. Correlations of tea and herbal infusion HPS activity with total phenolic content determined using the Folin-Ciocalteu assay (FC-GAE) (0.81 and 0.93), ferric reducing/antioxidant power (FRAP) (0.97 and 0.92), 1,1-diphenyl-2-picrylhydrazyl (DPPH) (0.77 and 0.80), and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging (0.86 and 0.86) were statistically significant. Correlations between relative antioxidant capacity index (RACI), calculated by assigning all applied assays equal weight, and HPS (0.98), FRAP (0.97), ABTS (0.89), and DPPH (0.89) confirmed DC polarographic assay reliability when applied individually. Correlation analysis, ANOVA, and Levene and Tukey's HSD tests unequivocally confirmed this reliable, rapid, and low-cost assay validity, clearly demonstrating its advantages over spectrophotometric assays applied.

Reference values of aortic pulse wave velocity in a large healthy population aged between 3 and 18 years.

OBJECTIVE: The measurement of aortic pulse wave velocity (PWV(ao)) is an accepted marker in stratifying individual cardiovascular risk in adults. There is an increasing volume of evidence concerning impaired vascular function in different diseases in paediatric populations, but, unfortunately, only a few studies are available on the measurement of normal PWV(ao) values in children. The aim of our study was to determine the reference values of PWV(ao) in a large healthy population using a newly developed technique. METHODS: Three thousand, three hundred and seventy-four healthy individuals (1802 boys) aged 3-18 years were examined by an invasively validated, occlusive, oscillometric device. RESULTS: The mean PWV(ao) values increased from 5.5 ± 0.3 to 6.5 ± 0.3 m/s (P < 0.05) in boys and from 5.6 ± 0.3 to 6.4 ± 0.3 m/s (P < 0.05) in girls. The increase, however, was not constant, and the values exhibited a flat period between the ages of 3 and 8 years in both sexes. The first pronounced increase occurred at the age of 12.1 years in boys and 10.4 years in girls. Moreover, between the ages of 3 and 8 years, the brachial SBP and mean blood pressures increased continuously and gradually, whereas the PWV(ao) remained unchanged. By contrast, beyond the age of 9 years, blood pressure and aortic stiffness trends basically moved together. CONCLUSION: Our study provides the largest database to date concerning arterial stiffness in healthy children and adolescents between the ages of 3 and 18 years, and the technology adopted proved easy to use in large paediatric populations, even at a very young age.

Polarographic study of hydrogen peroxide anodic current and its application to antioxidant activity determination.

Behavior of hydrogen peroxide in alkaline medium has been studied by direct current (DC) polarography with dropping mercury electrode (DME) aiming to apply it in antioxidant (AO) activity determination. Development of a peroxide anodic current having form of a peak, instead of common polarographic wave, has been investigated. As a base for this investigation the interaction of H(2)O(2) with anodically dissolved mercury was followed. Formation of mercury complex [Hg(O(2)H)(OH)] has been confirmed. The relevant experimental conditions, such as temperature, concentration and pH dependence, as well as time stability of hydrogen peroxide anodic current, have been assessed. Development of an AO assay based on decrease of anodic current of hydrogen peroxide in the presence of antioxidants (AOs) has been described. Under optimized working conditions, a series of benzoic acids along with corresponding cinnamate analogues have been tested for hydrogen peroxide scavenging activity. In addition, the assay versatility has been confirmed on various complex samples.

Polarographic assay based on hydrogen peroxide scavenging in determination of antioxidant activity of strong alcohol beverages.

Total antioxidant (AO) activity of strong alcohol beverages such as wine and plum brandies, whiskeys, herbal and sweet fruit liqueurs have been assessed using a polarographic assay based on hydrogen peroxide scavenging (HPS). Rank of order of total AO activity, expressed as percentage of decrease of anodic oxidation current of hydrogen peroxide, was found analogous with total phenolic content estimated by Folin-Ciocalteau (FC) assay and radical scavenging capacity against the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). Application of the assay for surveying of a quarter century long maturation of plum brandy in oak barrel was demonstrated. In addition, influence of different storage conditions on preservation of AO activity of some herbal liqueurs was surveyed. Wide area of application of this simple, fast, low cost and reliable assay in analysis and quality monitoring of various strong alcohol beverages was confirmed.

Kinetic method for the determination of traces of thyroxine by its catalytic effect on the Mn(III) metaphosphate-As(III) reaction.

A new, highly sensitive and simple kinetic method for the determination of thyroxine was proposed. The method was based on the catalytic effect of thyroxine on the oxidation of As(III) by Mn(III) metaphosphate. The kinetics of the reaction was studied in the presence of orthophosphoric acid. The reaction rate was followed spectrophotometrically at 516 nm. It was established that orthophosphoric acid increased the reaction rate and that the extent of the non-catalytic reaction was extremely small. A kinetic equation was postulated and the apparent rate constant was calculated. The dependence of the reaction rate on temperature was investigated and the energy of activation and other kinetic parameters were determined. Thyroxine was determined under the optimal experimental conditions in the range 7.0 x 10(-9) to 3.0 x 10(-8) mol L(-1) with a relative standard deviation up to 6.7% and a detection limit of 2.7 x 10(-9) molL(-1). In the presence of 0.08 mol L(-1) chloride, the detection limit decreased to 6.6 x 10(-10) mol L(-1). The proposed method was applied for the determination of thyroxine in tablets. The accuracy of the method was evaluated by comparison with the HPLC method.

Successful treatment of a primary uterine B-cell lymphoma with rituximab-CHOP immunochemotherapy.

We report the case of a 26 year old patient with a primary, Ann Arbor stage IE, diffuse large B-cell lymphoma of the uterine corpus. The patient was admitted to our hospital because of a one year history of vaginal contact bleeding. Final diagnosis was based on the histological and immunohistochemical evaluation of a specimen obtained by fractionated cervical and uterine curettage. Further staging has not revealed any other localization of the disease. Antilymphoma treatment was started with CHOP combined with rituximab and resulted complete remission. This is the first reported case of an uterine lymphoma treated by rituximab-based immunochemotherapy.

The importin-beta P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope.

Three of the four independently induced Ketel(D) dominantnegative female sterile mutations that identify the Drosophila importin-beta gene, originated from a C4114--> T transition and the concurrent replacement of Pro446 by Leu (P446L). CD spectroscopy of representative peptides with Pro or Leu in the crucial position revealed that upon the Pro-->Leu exchange the P446L mutant protein loses flexibility and attains most likely an open conformation. The P446L mutation abolishes RanGTP binding of the P446L mutant form of importin-beta protein and results in increased RanGDP binding ability. Notably, the P446L mutant importin-beta does not exert its dominant-negative effect on nuclear protein import and has no effect on mitotic spindle-related functions and chromosome segregation. However, it interferes with nuclear envelope formation during mitosis-to-interphase transition, revealing a novel function of importin-beta.

[Prognostic significance of selected oncogene and suppressor gene expression in follicular thyroid carcinoma]. / Prognostyczne znaczenie ekspresji wybranych onkogenów i genów supresorowych w raku pecherzykowym tarczycy.

Oncogene and suppressor gene expression (cyclin D, p21WAF1, nm23-H1, Rb1, p16INK4A, and p53) was evaluated in 23 follicular thyroid carcinomas diagnosed in 20 women and 3 men operated or reoperated in Institute of Oncology in Gliwice in years 1992-1999. Positive reaction with p16INK4A, Rb1 and cyclin D1 antibodies was observed in all tumors, with nm23-H1 in 22 cases. The presence of p21WAF1 was stated in 8 cases (34.8%) and p53 in 7 cases (30.4%). A simultaneous presence of expression of p53 and lack of expression of p21WAF1 was stated three times and in two cases were accompanied by distant metastases. This pattern of expression was only rarely observed in minimally invasive follicular cancer. The prognostic significance of simultaneous immunohistochemical analysis of p53 and p21WAF1 in follicular thyroid carcinoma is suggested and has to be proved in further studies.

Genotoxicity assessment of new synthesized acridine derivative--3,6-diamino-10-methyl-9,10-dihydroacridine.

A new synthesized acridine derivative, 3,6-diamino-10-methyl-9, 10-dihydroacridine (AcrH), was tested for in vitro reverse mutations with Salmonella TA strains, chromosome aberrations and sister chromatid exchanges (SCE) in human lymphocytes, and for in vivo chromosome aberrations in bone marrow of mice. Using the classic plate incorporation method, mutagenicity of AcrH in bacterial cells (TA97a, TA98, TA100 and TA102) was observed in the experiments performed with, and without, rat liver S9 metabolic activation. The reverse mutation assay showed no difference in mutagenic activity between AcrH and acriflavine (Acr(+)) in the test with TA97. The results of in vitro chromosome aberrations assay revealed potential clastogenicity. The test using macroculture of human lymphocytes induced mainly chromatid gaps. The experiments with human lymphocytes revealed SCE-inducing effect of AcrH and Acr(+). In an in vivo study, AcrH given intraperitoneally to Balb/c mice did not cause any significant increase in the percentage of cells with aberrations compared to the negative control.

Mutagenic activity of 3,6-diamino-10-methyl-9,10-dihydroacridine in Salmonella typhimurium cells.

Mutagenic evaluation of 3,6-diamino-10-methyl-9,10-dihydroacridine (AcrH), a new synthesized acridine derivative was undertaken using short-term in vitro test. The mutagenic potential of AcrH was evident from the reverse mutation induced in the presence and absence of S9-mix of Salmonella typhimurium TA97a, TA98, TA100 and TA102 cells. The levels of the mutagenic activity of AcrH in TA97a are comparable with that of acriflavine.

[Immunopathology of Graves'-Basedow disease]. / Immunopatologia choroby Gravesa-basedowa.

The pathogenesis Graves' disease, an autoimmune disorder, is not fully understood. Immune disturbances, genetic predisposition and environmental factors, affecting thyroid gland, appear to play the main role in contribution and development of the disease. Autoreactive T lymphocyte infiltrates in the thyroid gland and/or in the retroorbital tissues and autoantibodies to TSH receptor detected in almost all of the patients, have been considered to be responsible for hyperthyroidism, ophthalmopathy, pretibial dermopathy and goiter. In this review, we describe some recent reports on the pathophysiological and immunological aspects of the thyroidal and extrathyroidal manifestations of the Graves' disease.