Heparin-induced thrombocytopenia type II (HIT II), as stated in the literature, occurs in about 3% of all patients and in 0.1-5% of surgical patients. Thrombosis develops in 20-64% of patients with ...HIT. The mortality rate in HIT II has not decreased using non-heparin treatment with anticoagulants such as argatroban and lepirudin. An improved understanding of the pathophysiology of HIT may help identify targeted therapies to prevent thrombosis without subjecting patients to the risk of intense anticoagulation. The review will summarize the current knowledge about the pathogenesis of HIT II, potential new therapeutic targets related to it, and new treatments being developed. HIT II pathogenesis involves multi-step immune-mediated pathways dependent on the ratio of PF4/heparin and platelet, monocyte, neutrophil, and endothelium activation. For years, only platelets were known to take part in HIT II development. A few years ago, specific receptors and signal-induced pathways in monocytes, neutrophils and endothelium were revealed. It had been shown that the cells that had become active realised different newly formed compounds (platelet-released TF, TNFα, NAP2, CXCL-7, ENA-78, platelet-derived microparticles; monocytes-TF-MPs; neutrophils-NETs), leading to additional cell activation and consequently thrombin generation, resulting in thrombosis. Knowledge about FcγIIa receptors on platelets, monocytes, neutrophils and FcγIIIa on endothelium, chemokine (CXCR-2), and PSGL-1 receptors on neutrophils could allow for the development of a new non-anticoagulant treatment for HIT II. IgG degradation, Syk kinase and NETosis inhibition are in the field of developing new treatment possibilities too. Accordingly, IdeS and DNases-related pathways should be investigated for better understanding of HIT pathogenesis and the possibilities of being the HIT II treatment targets.
: One of the reasons for thrombosis in chronic heart failure (CHF) might be reactive forms of oxygen activating platelets. The aim of this study was to evaluate the effect of oxidant hypochlorous ...acid (HOCl) on platelet aggregation and dityrosine concentration in CHF patients and healthy controls. Materials and Methods: CHF patients (
67) and healthy (
31) were investigated. Heart echoscopy, 6-min walking test, complete blood count, platelet aggregation, and dityrosine concentration were performed. Platelet aggregation and dityrosine concentration were measured in plasma samples after incubation with different HOCl concentrations (0.15, 0.0778, and 0.0389 mmol/L). Results: Platelet aggregation without oxidant was lower (
= 0.049) in CHF patients than in controls. The spontaneous platelet aggregation with oxidant added was higher in CHF patients (
= 0.004). Dityrosine concentration was also higher (
= 0.032) in CHF patients. Platelet aggregation was the highest in samples with the highest oxidant concentration in both healthy controls (
= 0.0006) and in CHF patients (
= 0.036). Platelet aggregation was higher in NYHA III group in comparison to NYHA II group (
= 0.0014). Concentration of dityrosine was significantly higher in CHF samples (
= 0.032). The highest concentration of dityrosine was obtained in NYHA IV group samples (
0.05). Intensity of platelet aggregation, analyzed with ADP, was correlated with LV EF (r 0.42,
= 0.007). Dityrosine concentration was correlated with NYHA functional class (r 0.27,
0.05).
The increase in platelet aggregation in CHF and healthy controls shows the oxidant effect on platelets. The increase in dityrosine concentration in higher NYHA functional classes shows a higher oxidative stress in patients with worse condition.
In the present study fatty acid (FA) composition in four main groups of dairy products was determined to investigate their development during processing and storage. Fresh cheese, sour cream, butter, ...and ultra-high
temperature (UHT) milk representing differences in technological approach were chosen for the study. Fatty acids methyl esters (FAME) were quantified using a gas chromatograph (GC) equipped with a mass spectrometer (MS) and a capillary column SP-2560. The concentrations and
profile of FA in final products were primarily dependent on the FA content of raw milk for UHT milk and fresh cheese production or in the raw cream for sour cream and butter. The shelf life had a significant impact (P<0.05) only in UHT milk and butter, whereby unsaturated fatty acids (UFA) and polyunsaturated fatty acids (PUFA) decreased significantly in UHT milk, while PUFA decreased significantly in butter.
U ovom je radu u četiri glavne vrste mliječnih proizvoda utvrđivan sastav masnih kiselina (FA), kao i njihov udio tijekom prerade i čuvanja. Kako bi se utvrdio utjecaj tehnološkog postupka, za istraživanje su odabrani svježi sir, kiselo vrhnje, maslac i trajno mlijeko obrađeno režimom UHT toplinske obrade. Metilni esteri masnih kiselina (FAME) određeni su pomoću plinskog kromatografa (GC) opremljenog masenim detektorom (MS) i kapilarnom kolonom SP-2560. Koncentracije i profil FA u krajnjim proizvodima su prije svega ovisili o
koncentraciji FA u sirovom mlijeku prije UHT obrade mlijeka ili proizvodnje svježeg sira, odnosno o udjelima FA u svježem siru i sirovom
vrhnju. Rok trajanja imao je značajan utjecaj (P<0,05) samo u UHT obrađenom mlijeku i u maslacu gdje je utvrđen pad koncentracije nezasićenih (UFA - samo mlijeko) i višestrukonezasićenih (PUFA - mlijeko
i maslac) masnih kiselina
Prostate cancer is on the rise in the European Union, and radiofrequency ablation (RFA) is one of the minimally invasive treatment options used for its treatment. Therefore, the aim of this study was ...to investigate and analyze the effects of RFA on prostate tissues.
A standard prostate RFA procedure was performed on 13 non-purebred dogs in three sessions: no cooling (NC), cooling with a 0.1% NaCl solution (C.01), and cooling using a 0.9% NaCl solution (C.09). Microtome-cut 2-3 µm sections of prostate samples were stained with hematoxylin and eosin and further examined.
A histopathologic evaluation identified four zones of exposure: direct, application, necrosis, and transitional, as the damage on tissues decreased going further from the ablation site. The areas and perimeters of these zones were calculated, and geometric shapes of ablative lesions were evaluated using the quotient formula. Areas and perimeters of prostate tissue lesions in the NC and C.09 sessions were of similar size, whereas those found in C.01 were statistically significantly smaller. Lesions observed in session C.01 were of the most regular geometric shape, while the most irregular ones were found in session C.09. The shapes of lesions closest to the ablation electrode were the most irregular, becoming more regular the further away from the electrode they were.
Prostate RFA leads to tissue damage with distinct morphological zones. Notably, the prostate lesions were the smallest and the most regular in shape after RFA procedures using the 0.1% NaCl cooling solution. It can be argued that smaller ablation sites may result in smaller scars, thus allowing for faster tissue healing if the blood flow and innervation at the ablation site are not compromised.
The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present ...study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel’s neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.
Aluminum accumulation, glutathione (GSH) and malondialdehyde (MDA) concentrations as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in erythrocytes and brain and ...liver homogenates of BALB/c mice treated with Al
(7.5 mg/kg/day (0.15 LD
) as AlCl
(37.08 mg/kg/day), whereas HCl (30.41 mg/kg/day) was used as Cl
control, the treatments were performed for 21 days, i.p., in the presence and absence of rosmarinic acid (0.2805 mg/kg/day (0.05 LD
), 21 days, i.g.) or carvacrol (0.0405 mg/kg/day (0.05 LD
), 21 days, i.g.). The treatment with AlCl
increased GSH concentration in erythrocytes only slightly and had no effect on brain and liver homogenates. Rosmarinic acid and carvacrol strongly increased GSH concentration in erythrocytes but decreased it in brain and liver homogenates. However, AlCl
treatment led to Al accumulation in mice blood, brain, and liver and induced oxidative stress, assessed based on MDA concentration in the brain and liver. Both rosmarinic acid and carvacrol were able to counteract the negative Al effect by decreasing its accumulation and protecting tissues from lipid peroxidation. AlCl
treatment increased CAT activity in mice brain and liver homogenates, whereas the administration of either rosmarinic acid or carvacrol alone or in combination with AlCl
had no significant effect on CAT activity. SOD activity remained unchanged after all the treatments in our study. We propose that natural herbal phenolic compounds rosmarinic acid and carvacrol could be used to protect brain and liver against aluminum induced oxidative stress leading to lipid peroxidation.
In the present study fatty acid (FA) composition in four main groups of dairy products was determined to investigate their development during processing and storage. Fresh cheese, sour cream, butter, ...and ultra-high temperature (UHT) milk representing differences in technological approach were chosen for the study. Fatty acids methyl esters (FAME) were quantified using a gas chromatograph (GC) equipped with a mass spectrometer (MS) and a capillary column SP-2560. The concentrations and profile of FA in final products were primarily dependent on the FA content of raw milk for UHT milk and fresh cheese production or in the raw cream for sour cream and butter. The shelf life had a significant impact (P<0.05) only in UHT milk and butter, whereby unsaturated fatty acids (UFA) and polyunsaturated fatty acids (PUFA) decreased significantly in UHT milk, while PUFA decreased significantly in butter.
Though heart failure can mainly be caused by systolic or diastolic dysfunction, the impairments of the neurohormonal, immune, and hemostatic systems are observed too. Therefore, it is not easy to ...determine etiology of the syndrome. Parameters that can be helpful to predict chronic heart failure, to evaluate its course and the risk of complications are still being searched. The aim of this article is to review the recent studies in order to find the links between the coagulation system and the development of chronic heart failure. Stress is a key factor for the development of most diseases including chronic heart failure too. Signals of emotional and physical stress via particular structures trigger an increase in concentrations of the following hormones: noradrenaline, renin, angiotensin II, aldosterone, vasopressin. It is proved that it causes the disorders of the coagulation system: an increase in the following factors of plasma coagulation (fibrinogen, VII, VIII, fibrinopeptide A, thrombin-antithrombin complex), fibrinolysis (D-dimer), endothelium (interleukin 1, endothelin 1, vascular cell adhesion molecules, endothelial growth factor), platelet activity (von Willebrand factor, intercellular adhesion molecules, platelet factor 4, P-selectin, thromboxane A(2), thromboglobulin, CD63P) and cytokines (tumor necrosis factor, interleukin 6) and decrease in E-selectin. The role of particular coagulation factors for the development of chronic heart failure has not been understood yet. Thus, it is necessary to carry out further studies.
An insufficient supply of oxygen to the heart influences the process of protein synthesis. The aim of this study was to determine the effect of the Polyscias filicifolia Bailey biomass tincture on ...the protein synthesis process in a heterogeneous translation system from the isolated pig heart.
The effect of anoxia was evaluated after 20- and 90-minute anoxia. With the aim to determine the effect of Polyscias, the pig hearts were perfused with a buffer containing the Polyscias filicifolia Bailey biomass tincture. To determine the rate and the level of translation, the incorporation of (14)C-leucine into translational products in a cell-free system was measured.
The protein synthesis level decreased by 23%-42% when the translation system containing cytosol from the anoxic heart was used. When the translation system containing a ribosomal fraction after 20-minutes anoxia was used, the protein synthesis level was the same as in the control. In the case of 90-minute anoxia, it decreased by 16%. The protein synthesis rate and the level in the translation system containing cytosol from the heart after 20-minute anoxic perfusion with the buffer containing Polyscias was the same as in the control.
A decrease in the protein synthesis rate and the level after 20-minute anoxia was determined by changes in cytosol. On the other hand, 90-minute anoxia caused changes in cytosol and the ribosomal fraction. The Polyscias filicifolia Bailey biomass tincture restored the protein synthesis process acting on the components of the translation system in cytosol and the ribosomal fraction.
Flavonol (−)-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, ...their mechanism of action has not been fully elucidated. We studied effects of (−)-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (−)-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control) on substrate-driven (State 2) mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (−)-Epicatechin at higher concentrations (from 0.27 µg/mL) significantly decreased (up to 15%) substrate- and ADP-driven (State 3) mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7–17.9 ng/mL) inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (−)-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (−)-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.
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