Blood Plasma Serotonin and von Willebrand Factor as Biomarkers of Unstable Angina Progression Toward Myocardial Infarction

Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess the utility of both as prognostic markers of UA complications. Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator. Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 [6.0, 60.0] and 18.0 [3.9, 80.0]) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively. Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction

Difference in coagulation markers in acute and one year post acute ischemic stroke

Background and purpose: Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis of cerebral ischemia. However, its relevance to post-acute disease period requires further elucidation. This study aimed to characterize whether hypercoagulation markers differ for patients in acute and the same patients in the post acute phase of ischemic stroke. Materials and methods: Systemic generation of hemostasis markers was monitored and fraction composition was described during one year of disease development and treatment. Results: Increased concentration of the markers of hypercoagulation in blood plasma of patients in acute as well as one year past acute phase ischemic stroke were shown. Thus, not all markers of hypercoagulation become relevant to norm one year past ischemic stroke. It\u27s the first time characterization of the coagulation markers in acute and post acute period of the absolutely same group of patients was done. Our study demonstrates the difference in quantity and quality of the fractions of proteins with prothrombin origin and soluble fibrin monomer complexes which could be used as a potential target for the prevention of the stroke repetition. Conclusions: We assume that prothrombin plays the most important role in the development of pathology tested, hence it may provide future targets for therapeutic strategies.</p

Fragmenti kolagena male molekularne mase poboljšavaju masene i upalne parametre masnog tkiva pretilih štakora

Research background. Despite clearly recognized links between increased body mass and increased risk for various pathological conditions, therapeutic options to treat obesity are still very limited. The aim of the present study is to explore the effect of low-molecular-mass collagen fragments obtained from the scales of Antarctic wild marine fish on rats\u27 visceral and subcutaneous white adipose tissue in a high-calorie diet-induced obesity model. Experimental approach. The study was conducted on outbred rats, which were divided into 3 experimental groups: (i) control, consuming standard food (3.81 kcal/g), (ii) obese group, consuming a high-calorie diet (5.35 kcal/g), and (iii) obese group, consuming a high-calorie diet (5.35 kcal/g) with intragastric administration of low-molecular-mass collagen fragments (at a dose 1 g/kg of body mass during 6 weeks). Low-molecular-mass collagen fragments were obtained by a procedure that included collagen extraction from fish scales and enzymatic hydrolysis with pepsin. Apart from hematoxylin and eosin staining, fibrosis level was assessed by histochemical Van Gieson’s trichrome picrofuchsin staining, and mast cells were analysed by toluidine blue O staining. Results and conclusions. Group treated with low-molecular-mass fragments of collagen exhibited decreased rate of mass gain, relative mass, area occupied by collagen fibre of both visceral and subcutaneous adipose tissue, and cross-sectional area of both visceral and subcutaneous adipocytes. Treatment with low-molecular-mass fragments of collagen reduced the infiltration of immune cells, number of mast cells and their redistribution back to the septa. This was also accompanied by a decreased number of the crown-like structures formed by the immune cells, which are markers of chronic inflammation that accompanies obesity. Novelty and scientific contribution. This is the first study that reports the anti-obesity effect of low-molecular-mass fragments produced as a result of controlled hydrolysis of collagen from the scales of Antarctic wild marine fish in the in vivo model. Another novelty of this work is the observation that the tested collagen fragments not only reduce the body mass, but also improve the morphological and inflammatory parameters (decrease in the number of crown-like structures, immune cell infiltration, fibrosis and mast cells). Altogether, our work suggests that low-molecular-mass collagen fragments are a promising candidate for amelioration of some comorbidities linked to obesity.Pozadina istraživanja. Usprkos jasno utvrđenoj povezanosti povećane tjelesne mase s većim rizikom razvoja različitih patoloških oboljenja, mogućnosti liječenja pretilosti su još uvijek vrlo ograničene. Svrha je ovoga rada bila ispitati učinak fragmenata kolagena male molekularne mase, dobivenih iz ljuski morskih riba s područja Antarktika, na visceralno i potkožno masno tkivo štakora s dijabetesom uzrokovanim visokokaloričnom prehranom. Eksperimentalni pristup. Istraživanje je provedeno na nesrođenim sojevima štakora, podijeljenim u tri eksperimentalne skupine: (i) kontrolna skupina, koja je primala standardnu prehranu (3,81 kcal/g), (ii) pretila skupina koja je primala visokokaloričnu prehranu (5,35 kcal/g), i (iii) pretila skupina koja je primala visokokaloričnu prehranu (5,35 kcal/g) i intragastrično fragmente kolagena male molekularne mase (1 g po kg tjelesne mase tijekom 6 tjedana). Fragmenti kolagena male molekularne mase dobiveni su ekstrakcijom kolagena iz ljusaka ribe i njegovom enzimskom hidrolizom pomoću pepsina. Stupanj fibroze masnog tkiva je, osim bojenjem hematoksilin eozinom, utvrđen Van Giesonovim bojenjem, a mastociti su ispitani bojenjem toluidinskim modrilom. Rezultati i zaključci. Skupina štakora koja je primala fragmente kolagena male molekularne mase sporije je dobivala na masi i relativnoj masi, a kolagenska vlakna su zauzimala manju površinu njihovog visceralnog i potkožnog masnog tkiva te presjeka visceralnih i potkožnih adipocita. Intragastričnom primjenom fragmenata kolagena male molekularne mase smanjili su se infiltracija imunoloških stanica, broj mastocita i njihova redistribucija u septe. Također se smanjio broj krunastih struktura koje tvore makrofagi, a koje su markeri kronične upale povezane s pretilošću. Novina i znanstveni doprinos. Ovo je prvo istraživanje in vivo o utjecaju fragmenata kolagena dobivenih kontroliranom hidrolizom ljusaka morskih riba iz područja Antarktika na smanjenje tjelesne mase. Još jedna novina ovoga rada je opažanje da ispitani fragmenti kolagena nisu samo smanjili tjelesnu masu, već i poboljšali morfološke i upalne parametre (smanjili su se broj krunastih struktura, infiltracija imunostanica, fibroza i broj mastocita). Zaključno, rad je pokazao da fragmenti kolagena male molekularne mase mogu ublažiti neke komorbiditete povezane s pretilošću

Proteolytic parameter changes in the plasma of patients with bladder cancer – depending on tumor stage

Bladder cancer (BC) is a worldwide common disease with a high mortality rate. Recognizing the dynamic changes in plasma that proteases and their inhibitors undergo might be valuable in understanding the carcinogenesis of invasive bladder cancer and in identifying BC patients with poor prognosis. This study aims to determine the activity of the proteolytic enzyme system and their inhibitors in patients with BC. In this paper, the total proteolytic activity, the activity of matrix metalloproteases (MMPs) and serine proteases was analyzed by the method of caseinolytic activity. For detection of activity of some inhibitors of proteolysis, we used the unified method for determining the activity of alpha-1-antitrypsin (α1A) and alpha-2-Macroglobulin (α2M) in human plasma. The level of medium-mass molecules (MMM) was assessed spectrophotometrically by applying the Nikolaichik method

Influence of the complex drug Cocarnit on the sciatic nerve in the development of diabetic polyneuropathy in rats

Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP

Low-Molecular-Mass Fragments of Collagen Improve Parameters Related to Mass and Inflammation of the Adipose Tissue in the Obese Rat

Research background. Despite clearly recognized links between increased body mass and increased risk for various pathological conditions, therapeutic options to treat obesity are still very limited. The aim of the present study is to explore the effect of low-molecular-mass collagen fragments obtained from the scales of Antarctic wild marine fish on rats' visceral and subcutaneous white adipose tissue in a high-calorie diet-induced obesity model. Experimental approach. The study was conducted on outbred rats, which were divided into 3 experimental groups: (i) control, consuming standard food (3.81 kcal/g), (ii) obese group, consuming a high-calorie diet (5.35 kcal/g), and (iii) obese group, consuming a high-calorie diet (5.35 kcal/g) with intragastric administration of low-molecular-mass collagen fragments (at a dose 1 g/kg of body mass during 6 weeks). Low-molecular-mass collagen fragments were obtained by a procedure that included collagen extraction from fish scales and enzymatic hydrolysis with pepsin. Apart from hematoxylin and eosin staining, fibrosis level was assessed by histochemical Van Gieson’s trichrome picrofuchsin staining, and mast cells were analysed by toluidine blue O staining. Results and conclusions. Group treated with low-molecular-mass fragments of collagen exhibited decreased rate of mass gain, relative mass, area occupied by collagen fibre of both visceral and subcutaneous adipose tissue, and cross-sectional area of both visceral and subcutaneous adipocytes. Treatment with low-molecular-mass fragments of collagen reduced the infiltration of immune cells, number of mast cells and their redistribution back to the septa. This was also accompanied by a decreased number of the crown-like structures formed by the immune cells, which are markers of chronic inflammation that accompanies obesity. Novelty and scientific contribution. This is the first study that reports the anti-obesity effect of low-molecular-mass fragments produced as a result of controlled hydrolysis of collagen from the scales of Antarctic wild marine fish in the in vivo model. Another novelty of this work is the observation that the tested collagen fragments not only reduce the body mass, but also improve the morphological and inflammatory parameters (decrease in the number of crown-like structures, immune cell infiltration, fibrosis and mast cells). Altogether, our work suggests that low-molecular-mass collagen fragments are a promising candidate for amelioration of some comorbidities linked to obesity

Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety

International audienceThiosulfonate derivatives based on quinones were synthesized for studying "structure-activity relationship" compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed