Immunomodulatory effects of anticoagulant warfarin in rats

Варфарин (4-хидроксикумарин) је антагонист витамина К. Овај кумарински дериват се користи као антикоагулантни родентицид и као терапеутско средство у профилакси тромбоемболијских болести. Антикоагулантни ефекат варфарина се заснива на инхибицији корака, који зависе од витамина К, у синтези бројних фактора коагулације у јетри. Захваљујући инхибицији циклуса витамина К, варфарин утиче и на друге протеине неопходне за биолошке процесе ван хемостазе (раст и калцификацију костију, раст глаткомишићних ћелија васкулатуре и мезангијских ћелија и друге), доводећи до штетних последица. Варфарин инхибира и процесе који нису у вези са витамином К, укључујући раст тумора. Малобројни подаци указују да овај агенс може да делује и на поједине аспекте имунске функције. Механизми деловања варфарина на имунски систем су, међутим, најмање познати. Ова дисертација је имала за циљ да испита имуномодулаторни потенцијал варфарина након његове епикутане и оралне примене код пацова. Акутни епикутани третман (три дана за редом у дози од 10 μg и 100 μg натријум варфарина) одговара професионалној или акциденталној изложености, а субакутни орални третман (30 дана у дози од 0.35 mg/L и 3.5 mg/L натријум варфарина у пијаћој води) одговара терапијској примени. Проинфламаторни и имуномодулаторни потенцијал варфарина је испитан анализом хуморалних параметара (концентрација акутно фазних протеина и проинфламаторног цитокина, интерлеукина 6 (IL-6) у плазми, као и активности основних ензима антиоксидативне одбране супероксид дисмутазе и каталазе у еритроцитима), као и ћелијских параметара [квантитативне и квалитативне промене леукоцита периферне крви, посебно полиморфонуклеарних леукоцита (PMN)] као показатеља запаљења на системском нивоу. Механизми дејства на полиморфонуклеарне ћелије периферне крви испитани су у погледу њихове оксидативне активности, продукције проинфламаторних цитокина, фактора некрозе тумора (TNF) и IL-6, способности адхезије, миграције и екстравазације у циљна ткива, коришћењем модела субкутано имплантираних стерилних поливинилских сунђера. Резултати су показали да варфарин доспева у организам и када се наноси на кожу и након оралне примене, судећи по продужењу протромбинског времена...Warfarin (4-hydroxycoumarin) is a vitamin K antagonist. This coumarin derivative is used as an anticoagulant rodenticide and as a therapeutic agent for the prophylaxis of thromboembolic disorders. The anticoagulant effect of warfarin is based on the inhibition of the steps which are dependent on Vitamin K in the synthesis of a number of coagulation factors in the liver. Owing to the inhibition of the vitamin K cycle, warfarin also affects the other proteins which are necessary for the biological processes apart from hemostasis (growth and calcification of bones, vascular smooth muscle cells, mesangial cells and others), leading to harmful effects. Warfarin also inhibits the processes which are not related to vitamin K, including the growth of tumors. Few data suggest that this agent may act on certain aspects of immune function. Mechanisms of action of warfarin on the immune system are, however, the least known. This study was aimed to investigate the immunomodulatory potential of warfarin after its epicutaneous and oral administration in rats. The acute epicutaneous treatment (within three consecutive days in doses of 10 μg and 100 μg sodium warfarin) corresponds to professional or accidental exposure, and the subacute oral treatment (30 days in doses of 0.35 mg/L and 3.5 mg/L sodium warfarin in drinking water) corresponds to the therapeutic use. The proinflammatory and immunomodulatory potential of warfarin has been tested by analyzing the humoral parameters (concentration of acute phase proteins and pro-inflammatory cytokines, interleukin 6 (IL-6) in the plasma, as well as the activities of basic enzymes of antioxidant defence, superoxide dismutase and catalase in erythrocytes) as well as the cell parameters [quantitative and qualitative changes in peripheral blood leukocytes, especially polymorphonuclear leukocytes (PMN)] as an indicator of inflammation at the system level. Mechanisms of effects to the peripheral blood polymorphonuclear cells were tested with regard to their oxidative activity, production of pro-inflammatory cytokines, tumor necrosis factor (TNF) and IL-6, ability of adhesion, migration and extravasation in the target tissues, using models of subcutaneously implanted sterile polyvinyl sponges. The results showed that warfarin comes into the organism both when it is applied on the skin and after oral administration, judging by the extension of prothrombin time..

Procena stepena aktivacije koncentrovanih trombocita tokom skladištenja na osnovu ekspresije membranskih glikoproteina

Evaluation of factors responsible for storage lesions of platelets derived from buffy-coat (PC-BC) during storage are still matter of large interest. To determine, on the basis of expression of specific platelet markers (membrane antigen) in the total population of PC-BC, the extent of their activation and/or damage during storage up to five days at 20±2ºC. PC-BC were stored under standard blood bank conditions. Activation of platelets was monitored by measuring percent of expression and MFI of surface glycoproteins. Measure was performed on day 1, 3, 5, using flow cytometer and fluorochrome labeled monoclonal antibodies against CD41, CD42a, CD42b, CD62p, CD63, and CD36, molecules and Annexin V. There were significant differences in the percent of expression of CD42b, CD42a, and CD36 on whole platelets, detected first and third day of storage. Also, there was significant increase of the percent of expression of CD62p between first and fifth day, and also between third and fifth days. Significant differences were detected in the percent of expression between first and fifth day for CD41 and CD36 antigens. In addition,, MFI increased for CD42a and CD36 at third and fifth day, but significantly decreased for CD41. Elevation of expression of platelet activation antigens on PC-BC stored for five days in liquid form were minimal (within norms). This result reflects well-preserved and highly conserved function of stored platelets.Ispitivanje činilaca odgovornih za lezije koncentrovanih trombocita dobijenih iz 'buffy coat'-a (KT-BC) tokom skladištenja su još uvek predmet velikog interesa. Na osnovu vrednosti ekspresije specifičnih trombocitnih markera (membranskih antigena) na ukupnoj populaciji KT, odrediti stepen njihove aktivacije i/ili oštećenja tokom skladištenja u tečnom stanju, do pet dana, na 20±2oC. KT-BC su skladišteni pod standardnim uslovima. Aktivacija KT je praćena na osnovu rezultata merenja procenta trombocita koji eksprimiraju površinske glikoproteine i prosečnog intenziteta fluorescencije (MFI) tj. gustine ekspresije ovih antigena. Merenja ekspresije površinskih antigena na KT-BC su rađena prvog, trećeg i petog dana skladištenja, korišćenjem protočnog citometra i monoklonskih antitela, obeleženih fluorohromima, na CD41, CD42a, CD42b,CD62p, CD63 i CD36 molekul, i Aneksina V. U odnosu na prvi dan, trećeg dana skladištenja utvrđeno je smanjenje procenta trombocita koji eksprimiraju CD42b, CD42a, i povećanje procenta trombocita koji eksprimiraju CD36. Petog dana skladištenja, procenat trombocita koji eksprimiraju CD41 je bio, u odnosu na prvi dan, smanjen, dok je procenat trombocita koji eksprimiraju CD62p i CD36 bio povećan. Razlika između trećeg i petog dana postojala je samo u procentu trom­bocita koji eksprimiraju CD62p. Vrednost MFI je porastao za CD42a i CD36 antigene od prvog do trećeg, kao i do petog dana skladištenja. Vrednost MFI za CD41 antigen je u ovom periodu značajno opala. Utvrđen je minimalno povišen procenat ekspresije pojedinih aktivacionih trombocitnih markera, koji nije izlazio izvan opsega referentnih vrednosti, što odražava dobro očuvanu funkciju trombocita skladištenih u tečnom stanju

Effect of pretreatment with omega-3 polyunsaturated fatty acids (PUFAs) on hematological parameters and platelets aggregation in patients during elective coronary artery bypass grafting

Bacground/Aim. Using omega-3 polyunsaturated fatty acids (PUFAs) in coronary artery bypass graft surgery (CABG) could provide protection against ischemicreperfusion damage, prevention of postoperative arrhythmia and attenuation of inflammatory response. However, omega-3 PUFAs inhibit cyclooxygenase (and thus decrease the synthesis of thromboxane A2 from arachidonic acid in platelets), which leads to decreased platelet aggregation. In cardiac surgery it is necessary to achieve a balance between inhibition and full platelets function. It is as well as important to closely follow hematological parameters, impaired by CABG itself. Therefore, the aim of the study was to establish the effects of pretreatment with omega- PUFAs on hematological parameters and plateletes aggregation in patients with elective CABG. Methods. This prospective, randomized, placebo-controlled, single-center trial was performed on parallel groups. The patients (n = 40) undergoing elective CABG were randomized receiving preoperative intravenous omega-3 PUFAs (Omegaven® 10%) infusion (the PUFAs group) or the same volume of 0.9% saline solution infusion (the control group). Infusion was given a day before surgery and repeated four hours before starting extracorporeal circulation (CPB) via the peripheral vein at single doses of 100 mL (25 mL/h). Platelet function analysis was performed using multiple electrode aggregometry (MEA, multiplate-analyzer) before starting CPB and 2 h postoperatively for the patients of both groups. Results. There were no clinically relevant differences in baseline characteristics between the groups. Hematological parameters were not significantly different between the groups pre-, intra- and postoperatively. During the first 24 h after surgery, the loss of blood was similar in the PUFAs and the control group (680 ± 274 mL and 608 ± 210 mL, respectively; p = 0.356). Postoperatively, platelet aggregation was not significantly different between the PUFAs and the control group in adenosine diphosphate (ADP) test (39 ± 11 and 42 ± 15, respectively; p = 0.701), arachidonic acid (ASPI) test (64 ± 24 and 70 ± 27, respectively; p = 0.525) and trombin receptor-activating peptide (TRAP) test (68 ± 25 and 75 ± 26, respectively; p = 0.396), while their aggregation in collagen (COL) test was statistically significantly lower in the PUFAs related to the control group (32 ± 15 and 47 ± 20, respectively; p = 0.009). Conclusion. Acute pretreatment with omega-3 PUFAs insignificantly affected the activity of platelets and did not influence postoperative blood loss

Sojne razlike u toksičnosti antagoniste vitamina K varfarina kod pacova

Warfarin (3-(alpha-acetonylbenzy1)-4-hydroxy coumarin) is a vitamin K (VK) antagonist that inhibits vitamin K-dependent (VKD) processes, such as blood coagulation. It also exerts an influence on some non-VKD-related activities. In this study, the effect of sub-acute (30-day) oral warfarin (2 and 1 mg L-1) intake on hematological parameters was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), that differ in their sensitivity to certain chemicals. Greater susceptibility to the anticoagulant effect of 2 mg L-1 of warfarin was observed in AO rats and was associated with an increase in the relevant hematological parameters in this strain. Although both strains responded to 2 mg L-1 of warfarin with quantitative changes in the peripheral blood leukocytes, differential bone marrow and lung responses were observed. Strain-related differences in the pro-inflammatory activity of peripheral blood granulocytes and in mononuclear cell IFN-gamma production were observed. Recognition of differences in quantitative and qualitative effects of oral warfarin on processes other than hemostasis might be of relevance for those humans who are on warfarin therapy.Varfarin (3-α-acetonilbenzil)-4–hidroksikumarin) je antagonist vitamina K (VK) koji inhibira procese zavisne od ovog vitamina, uključujući koagulaciju krvi. Osim toga, on ispoljava i aktivnosti koje ne zavise od vitamina K kao što su anti-tumorska i imunomodulatorna aktivnost. U ovom radu je ispitan efekat subakutnog (30 dana) oralnog unosa varfarina na hematološke parametre i aktivnost leukocita periferne krvi kod dva soja pacova Albino Oxford (AO) i Dark Agouti (DA) koji se raz- likuju u osetljivosti na iste hemijske agense. Kod jedinki AO soja zapažena je veća smrtnost nakon konzumiranja doze od 4 mg L–1 kao i veća osetljivost na antikoagulantno dejstvo varfarina pri nižim dozama (2 mg L–1) koje je praćeno povećanjem nekih hematoloških parametara. Iako kod jedinki oba soja dolazi do povećanja broja neutrofilnih leukocita periferne krvi pri dozi od 2 mg L–1, promene u osnovnim proinflamatornim aktivnostima ovih ćelija su zapažene samo kod jedinki DA soja. Promene u broju neutrofilnih leukocita u krvi DA jedinki su praćene povećanjem broja granulocitnih prekursora u koštanoj srži, dok prisustvo neutrofila u plućima AO jedinki ukazuje na razmenu ćelija između periferne krvi i plućnog intravaskularnog pula ćelija. Diferencijalne sojno–zavisne promene u aktivnosti mononuklearnih ćelija periferne krvi su takođe zapažene. Razlike u efektu oralno unetog varfarina mogu da imaju implikacije za osobe na oralnoj varfarinskoj terapiji

Strain differences in the toxicity of the vitamin K antagonist warfarin in rats

Warfarin (3-(α-acetonylbenzyl)-4-hydroxy coumarin) is a vitamin K (VK) antagonist that inhibits vitamin K-dependent (VKD) processes, such as blood coagulation. It also exerts an influence on some non-VKD-related activities. In this study, the effect of sub-acute (30-day) oral warfarin (2 and 1 mg L-1) intake on hematological parameters was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), that differ in their sensitivity to certain chemicals. Greater susceptibility to the anticoagulant effect of 2 mg L-1 of warfarin was observed in AO rats and was associated with an increase in the relevant hematological parameters in this strain. Although both strains responded to 2 mg L-1 of warfarin with quantitative changes in the peripheral blood leukocytes, differential bone marrow and lung responses were observed. Strain-related differences in the pro-inflammatory activity of peripheral blood granulocytes and in mononuclear cell IFN-γ production were observed. Recognition of differences in quantitative and qualitative effects of oral warfarin on processes other than hemostasis might be of relevance for those humans who are on warfarin therapy.Varfarin (3-α-acetonilbenzil)-4–hidroksikumarin) je antagonist vitamina K (VK) koji inhibira procese zavisne od ovog vitamina, uključujući koagulaciju krvi. Osim toga, on ispoljava i aktivnosti koje ne zavise od vitamina K kao što su anti-tumorska i imunomodulatorna aktivnost. U ovom radu je ispitan efekat subakutnog (30 dana) oralnog unosa varfarina na hematološke parametre i aktivnost leukocita periferne krvi kod dva soja pacova Albino Oxford (AO) i Dark Agouti (DA) koji se raz- likuju u osetljivosti na iste hemijske agense. Kod jedinki AO soja zapažena je veća smrtnost nakon konzumiranja doze od 4 mg L–1 kao i veća osetljivost na antikoagulantno dejstvo varfarina pri nižim dozama (2 mg L–1) koje je praćeno povećanjem nekih hematoloških parametara. Iako kod jedinki oba soja dolazi do povećanja broja neutrofilnih leukocita periferne krvi pri dozi od 2 mg L–1, promene u osnovnim proinflamatornim aktivnostima ovih ćelija su zapažene samo kod jedinki DA soja. Promene u broju neutrofilnih leukocita u krvi DA jedinki su praćene povećanjem broja granulocitnih prekursora u koštanoj srži, dok prisustvo neutrofila u plućima AO jedinki ukazuje na razmenu ćelija između periferne krvi i plućnog intravaskularnog pula ćelija. Diferencijalne sojno–zavisne promene u aktivnosti mononuklearnih ćelija periferne krvi su takođe zapažene. Razlike u efektu oralno unetog varfarina mogu da imaju implikacije za osobe na oralnoj varfarinskoj terapiji.Projekat ministarstva br. 17303

Strain differences in the toxicity of the vitamin K antagonist warfarin in rats

Warfarin (3-(α-acetonylbenzyl)-4-hydroxy coumarin) is a vitamin K (VK) antagonist that inhibits vitamin K-dependent (VKD) processes, such as blood coagulation. It also exerts an influence on some non-VKD-related activities. In this study, the effect of sub-acute (30-day) oral warfarin (2 and 1 mg L-1) intake on hematological parameters was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), that differ in their sensitivity to certain chemicals. Greater susceptibility to the anticoagulant effect of 2 mg L-1 of warfarin was observed in AO rats and was associated with an increase in the relevant hematological parameters in this strain. Although both strains responded to 2 mg L-1 of warfarin with quantitative changes in the peripheral blood leukocytes, differential bone marrow and lung responses were observed. Strain-related differences in the pro-inflammatory activity of peripheral blood granulocytes and in mononuclear cell IFN-γ production were observed. Recognition of differences in quantitative and qualitative effects of oral warfarin on processes other than hemostasis might be of relevance for those humans who are on warfarin therapy.Varfarin (3-α-acetonilbenzil)-4–hidroksikumarin) je antagonist vitamina K (VK) koji inhibira procese zavisne od ovog vitamina, uključujući koagulaciju krvi. Osim toga, on ispoljava i aktivnosti koje ne zavise od vitamina K kao što su anti-tumorska i imunomodulatorna aktivnost. U ovom radu je ispitan efekat subakutnog (30 dana) oralnog unosa varfarina na hematološke parametre i aktivnost leukocita periferne krvi kod dva soja pacova Albino Oxford (AO) i Dark Agouti (DA) koji se raz- likuju u osetljivosti na iste hemijske agense. Kod jedinki AO soja zapažena je veća smrtnost nakon konzumiranja doze od 4 mg L–1 kao i veća osetljivost na antikoagulantno dejstvo varfarina pri nižim dozama (2 mg L–1) koje je praćeno povećanjem nekih hematoloških parametara. Iako kod jedinki oba soja dolazi do povećanja broja neutrofilnih leukocita periferne krvi pri dozi od 2 mg L–1, promene u osnovnim proinflamatornim aktivnostima ovih ćelija su zapažene samo kod jedinki DA soja. Promene u broju neutrofilnih leukocita u krvi DA jedinki su praćene povećanjem broja granulocitnih prekursora u koštanoj srži, dok prisustvo neutrofila u plućima AO jedinki ukazuje na razmenu ćelija između periferne krvi i plućnog intravaskularnog pula ćelija. Diferencijalne sojno–zavisne promene u aktivnosti mononuklearnih ćelija periferne krvi su takođe zapažene. Razlike u efektu oralno unetog varfarina mogu da imaju implikacije za osobe na oralnoj varfarinskoj terapiji.Projekat ministarstva br. 17303

Immunomodulatory effects of anticoagulant warfarin in rats

Варфарин (4-хидроксикумарин) је антагонист витамина К. Овај кумарински дериват се користи као антикоагулантни родентицид и као терапеутско средство у профилакси тромбоемболијских болести. Антикоагулантни ефекат варфарина се заснива на инхибицији корака, који зависе од витамина К, у синтези бројних фактора коагулације у јетри. Захваљујући инхибицији циклуса витамина К, варфарин утиче и на друге протеине неопходне за биолошке процесе ван хемостазе (раст и калцификацију костију, раст глаткомишићних ћелија васкулатуре и мезангијских ћелија и друге), доводећи до штетних последица. Варфарин инхибира и процесе који нису у вези са витамином К, укључујући раст тумора. Малобројни подаци указују да овај агенс може да делује и на поједине аспекте имунске функције. Механизми деловања варфарина на имунски систем су, међутим, најмање познати. Ова дисертација је имала за циљ да испита имуномодулаторни потенцијал варфарина након његове епикутане и оралне примене код пацова. Акутни епикутани третман (три дана за редом у дози од 10 μg и 100 μg натријум варфарина) одговара професионалној или акциденталној изложености, а субакутни орални третман (30 дана у дози од 0.35 mg/L и 3.5 mg/L натријум варфарина у пијаћој води) одговара терапијској примени. Проинфламаторни и имуномодулаторни потенцијал варфарина је испитан анализом хуморалних параметара (концентрација акутно фазних протеина и проинфламаторног цитокина, интерлеукина 6 (IL-6) у плазми, као и активности основних ензима антиоксидативне одбране супероксид дисмутазе и каталазе у еритроцитима), као и ћелијских параметара [квантитативне и квалитативне промене леукоцита периферне крви, посебно полиморфонуклеарних леукоцита (PMN)] као показатеља запаљења на системском нивоу. Механизми дејства на полиморфонуклеарне ћелије периферне крви испитани су у погледу њихове оксидативне активности, продукције проинфламаторних цитокина, фактора некрозе тумора (TNF) и IL-6, способности адхезије, миграције и екстравазације у циљна ткива, коришћењем модела субкутано имплантираних стерилних поливинилских сунђера. Резултати су показали да варфарин доспева у организам и када се наноси на кожу и након оралне примене, судећи по продужењу протромбинског времена...Warfarin (4-hydroxycoumarin) is a vitamin K antagonist. This coumarin derivative is used as an anticoagulant rodenticide and as a therapeutic agent for the prophylaxis of thromboembolic disorders. The anticoagulant effect of warfarin is based on the inhibition of the steps which are dependent on Vitamin K in the synthesis of a number of coagulation factors in the liver. Owing to the inhibition of the vitamin K cycle, warfarin also affects the other proteins which are necessary for the biological processes apart from hemostasis (growth and calcification of bones, vascular smooth muscle cells, mesangial cells and others), leading to harmful effects. Warfarin also inhibits the processes which are not related to vitamin K, including the growth of tumors. Few data suggest that this agent may act on certain aspects of immune function. Mechanisms of action of warfarin on the immune system are, however, the least known. This study was aimed to investigate the immunomodulatory potential of warfarin after its epicutaneous and oral administration in rats. The acute epicutaneous treatment (within three consecutive days in doses of 10 μg and 100 μg sodium warfarin) corresponds to professional or accidental exposure, and the subacute oral treatment (30 days in doses of 0.35 mg/L and 3.5 mg/L sodium warfarin in drinking water) corresponds to the therapeutic use. The proinflammatory and immunomodulatory potential of warfarin has been tested by analyzing the humoral parameters (concentration of acute phase proteins and pro-inflammatory cytokines, interleukin 6 (IL-6) in the plasma, as well as the activities of basic enzymes of antioxidant defence, superoxide dismutase and catalase in erythrocytes) as well as the cell parameters [quantitative and qualitative changes in peripheral blood leukocytes, especially polymorphonuclear leukocytes (PMN)] as an indicator of inflammation at the system level. Mechanisms of effects to the peripheral blood polymorphonuclear cells were tested with regard to their oxidative activity, production of pro-inflammatory cytokines, tumor necrosis factor (TNF) and IL-6, ability of adhesion, migration and extravasation in the target tissues, using models of subcutaneously implanted sterile polyvinyl sponges. The results showed that warfarin comes into the organism both when it is applied on the skin and after oral administration, judging by the extension of prothrombin time..

Flow cytometry analysis of platelet populations: usefulness for monitoring the storage lesion in pooled buffy-coat platelet concentrates

Background. Early detection of the platelet storage lesion is still a challenge in transfusion practice. Using flow cytometry, we evaluated the appearance of the storage lesion, based on the expression of platelet activation markers, in total platelets and platelet populations. Materials and methods. Buffy-coat-derived platelet concentrates were stored under standard conditions for 5 days. The expression of activation antigens CD42b, CD36, CD62p and phosphatidylserine on total platelets and populations of small, medium-sized and large platelets was analysed by flow cytometry on storage days 1, 3 and 5. Results. The activation/lesion on total platelets and each platelet population was detected on storage day 3, by the increased expression of CD36. On the same day, increased expression of CD42b and CD62p was detected, but only on large platelets. Small and medium-sized platelets had increased CD62p expression only on day 5. Externalisation of phosphatidylserine was not detected. Discussion. Evaluation of the level of expression of various activation markers on different platelet populations could be an additional valid analysis in cell quality control of platelet concentrates, and in the assessment of novel approaches to platelet concentrate manipulation

Gender-related differences in clinical presentation, electrocardiography signs, laboratory markers and outcome in patients with acute pulmonary embolism

Background/Aim. Acute pulmonary embolism (PE) is a potentially life threating event, but there are scarce data about genderrelated differences in this condition. The aim of this study was to identify gender-specific differences in clinical presentation, the diagnosis and outcome between male and female patients with PE. Methods. We analysed the data of 144 consecutive patients with PE (50% women) and compared female and male patients regarding clinical presentation, electrocardiography (ECG) signs, basic laboratory markers and six-month outcome. All the patients confirmed PE by visualized thrombus on the multidetector computed tomography with pulmonary angiography (MDCTPA), ECG and echocardiographic examination at admission. Results. Compared to the men, the women were older and a larger proportion of them was in the third tertile of age (66.0% vs 34.0%, p = 0.008). In univariate analysis the men more often had hemoptysis [OR (95% CI) 3.75 (1.16-12.11)], chest pain [OR (95% CI) 3.31 (1.57-7.00)] febrile state [OR (95% CI) 2.41 (1.12-5.22)] and pneumonia at PE presentation [OR (95% CI) 3.40 (1.25-9.22)] and less likely had heart decompensation early in the course of the disease [OR (95%CI) 0.48 (0.24-0.97)]. In the multivariate analysis a significant difference in the rate of pneumonia and acute heart failure between genders disappeared due to strong influence of age. There was no significant difference in the occurrence of typical ECG signs for PE between the genders. Women had higher level of admission glycaemia [7.7 mmol/L (5.5-8.2 mmol/L) vs 6.9 mmol/L (6.3-9.6 mmol/L), p = 0.006] and total number of leukocytes [10.5 x 109/L (8.8-12.7 x 109/L vs 8.7 x 109/L (7.0-11.6 x 109/L)), p = 0.007]. There was a trend toward higher plasma level of brain natriuretic peptide in women compared to men 127.1 pg/mL (55.0-484.0 pg/mL), p = 0.092] vs [90.3 pg/mL (39.2-308.5 pg/mL). The main 6-month outcomes, death and major bleeding, had similar frequencies in both sexes. Conclusion. There are several important differences between men and women in the clinical presentation of PE and basic laboratory findings which can influence the diagnosis and treatment of PE

Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage