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The alluvial development of the Great Hungarian Plain has greatly been determined by the subsidence of different areas in the Pannonian Basin. The temporal variation of subsidence rates significantly contributed to the avulsion and shifting of main rivers. This was the case in terms of the Hungarian Lower Danube when occupying its present day N-S directional course. The considerable role of tectonic forcing is also supported by the presence of different floodplain levels. Although, several channel forms are identifiable on these the timing of floodplain development has been reconstructed up till now mostly by the means of geomorphological analysis, and hardly any numerical dates were available. The main aim of this study is to provide the first OSL dates for palaeo-channels located on the high floodplain surface of the Hungarian Lower Danube, and to determine the maximum age of low and high floodplain separation on the Kalocsa Plain. For the analysis two meanders were sampled close to the edge of the step slope between the two levels. According to the results, the development of the investigated palaeo-meanders could be rapid. The formation of the older meander was dated to the Late Atlantic, while the possible separation of the high and low floodplain surfaces could start in the beginning of the Subboreal Phase.

During the Late Pelistocene-Holocene transition the fluvial landscape of the Great Hungarian Plain changed considerably as a consequence of tectonic, climatic and geomorphological factors. Geochronology, and especially luminescence dating, is a very important tool in reconstructing these changes. The present study focuses on the Lower-Tisza region and addresses the timing of the development of different floodplain levels. In the meantime the luminescence characteristics of the investigated alluvial sediments were also assessed, with a special emphasis on the comparison of silty fine grain and sandy coarse grain results, as in the given medium and low energy environment fine grain sediments are more abundant, however, based on the literature, coarse grain samples are more reliable in terms of luminescence dating. Measurements were performed on 12 samples originating from the point bars of two large palaeo-meanders, representing different floodplain levels along the river. Results indicate the applicability of both grain size fractions for dating purposes, though fine grain subsamples overestimate in average by 1.5 ka the ages yielded by coarse grain subsamples. Consequently, fine grain samples can be used for outlining only general trends, and results need to be controlled by coarse grain measurements where possible. Based on the ages received, the upper floodplain was actively formed until 13-15 ka, when incision and the development of an intermediate floodplain level started. The meander on the intermediate flood plain level developed then very actively until 9 ka. As indicated by the received age information the intensity of meander formation could be highly affected by climatic and especially vegetation control. However, reconstruction can be refined later by further sampling and the application of the results of the present paper.

It has long been the subject of empirical researches to examine the technical efficiency on farm (micro) level. Two main methods are most often used in the empirical literature: the non-parametric Data Envelopment Analysis (DEA) based on linear programming, and the Stochastic Frontier Analysis (SFA) introduced by Aigner, Lovell and Schmidt (1977). The present study aimed to investigate the technical efficiency of farms involved in agricultural activities in Hungary using the DEA-method and the data from the Hungarian FADN database. The technical efficiency was examined based on legal forms, farm size categories and the type of farming between 2001 and 2013.

Freshwater carbonates are unique depositions in the centre of the Carpathian Basin, with debated origin and age. Their formation on the sand covered area of the Danube-Tisza Interfluve is mainly related to lakes appearing in low lying interdune areas from time-totime. Carbonate deposition is governed by various processes, but in general it can be traced back to climatic and concomitant surface and subsurface hydrological variations. Therefore marl, limestone and dolomite layers can be a marker of environmental change. To identify the type of environmental change they may indicate absolute or numerical ages are needed. In previous studies this issue has been addressed by the means of radiocarbon dating. In the present study we attempted to bracket the age of freshwater carbonate formation with the help of optically stimulated luminescence dating and compared our results to radiocarbon data from the literature. In general, the luminescence properties of the investigated samples proved to be suitable for determining the age of the bedding and covering sediments. OSL dates confirmed previous interpretations that freshwater carbonate formation in the area could have a peak around 10,5 ka. However, the termination of the deposition could not be unambiguously determined at the present stage of the analysis. The compound geomorphology and sedimentology of the study area call for further investigations.

Abstract Background Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y12 antagonist is lacking. Multiple electrode aggregometry (MEA), which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y12 antagonists is missing. Design and Methods By performing in vitro and ex vivo experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y12 antagonists (clopidogrel in vivo, cangrelor in vitro) and aspirin (100 mg per day in vivo, and 1 mM or 5.4 mM in vitro) alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate. Results ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by in vitro addition of cangrelor (100 nM; p < 0.001) and by 64 ± 35% by oral clopidogrel (600 mg) intake (p < 0.05; values are means ± SD). Pre-incubation of blood with aspirin (1 mM) or oral aspirin intake (100 mg/day for 1 week) inhibited arachidonic acid (AA)-stimulated aggregation >95% and 100 ± 3.2%, respectively (p < 0.01). Aspirin did not influence ADP-induced platelet aggregation, either in vitro or ex vivo. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y12 blockade by cangrelor (100 nM) in vitro diminished AA-stimulated aggregation by 53 ± 26% (p < 0.01). A feasibility study in healthy volunteers showed that dual anti-platelet drug intake (aspirin and clopidogrel) could be selectively monitored by MEA. Conclusions Selective platelet inhibition by aspirin and P2Y12 antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.

The enzyme dUTPase has an essential role in maintaining genomic integrity. In mouse, nuclear and mitochondrial isoforms of the enzyme have been described. Here we present the isoform-specific mRNA expression levels in different murine organs during development using RT-qPCR. In this study, we analyzed organs of 14.5-day embryos and of postnatal 2-, 4-, 10-week- and 13-month-old mice. We demonstrate organ-, sex- and developmental stage-specific differences in the mRNA expression levels of both isoforms. We found high mRNA expression level of the nuclear isoform in the embryo brain, and the expression level remained relatively high in the adult brain as well. This was surprising, since dUTPase is known to play an important role in proliferating cells, and mass production of neural cells is completed by adulthood. Thus, we investigated the pattern of the dUTPase protein expression specifically in the adult brain with immunostaining and found that dUTPase is present in the germinative zones, the subventricular and the subgranular zones, where neurogenesis occurs and in the rostral migratory stream where neuroblasts migrate to the olfactory bulb. These novel findings suggest that dUTPase may have a role in cell differentiation and indicate that accurate dTTP biosynthesis can be vital, especially in neurogenesis., (© 2024. The Author(s).)

Background: In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response., Methods: Incomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20-40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4-5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K + concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis., Results: Ischemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K + concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15-20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD., Conclusions: We propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling., (© 2021. The Author(s).)

Verbal fluency is a cognitive function reflecting executive functions and the ability to retrieve the appropriate information from memory quickly. Previous studies reported conflicting results-impaired and intact verbal fluency-in autism spectrum disorder (ASD). Most studies concentrate on overall word productivity, errors, perseverations, clustering, or switching. We used a comprehensive approach to evaluate the reported discrepancy in the literature and introduced a new angle using the concept of word abstraction and imageability. Moreover, we analyzed the performance in two-time intervals (0-30 s and 31-60 s) to assess the temporal dynamics of verbal fluency and a possible activation or initiation deficit in autism. Sixteen adults with ASD and 16 neurotypical control participants, matched by gender, age, and education level, participated in our study. Contrary to our expectations, we did not find a significant difference between groups in word productivity, the number of errors, clustering, or temporal dynamics, neither in semantic nor in phonemic fluency tasks. Surprisingly, the two study groups' performance did not differ in terms of imageability or concreteness characteristics either. Our results raise the possibility that verbal fluency performance is intact in autism. We also suggest using a comprehensive approach when measuring fluency in autism. LAY SUMMARY: People with autism tend to think and communicate differently. In our study, we tested whether people with autism come up with more concrete or imageable words and whether their performance is better compared with neurotypicals in the beginning or in the later phase of a task measuring how many words they can produce in a minute. We did not detect any difference between the two groups; however, we recommend studying verbal fluency in autism from more and different angles in the future., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Carbon disulfide is an archetypal double-bonded molecule belonging to the class of group IV-group VI, AB 2 compounds. It is widely believed that, upon compression to several GPa at room temperature and above, a polymeric chain of type (-(C═S)-S-) n , named Bridgman's black polymer, will form. By combining optical spectroscopy and synchrotron X-ray diffraction data with ab initio simulations, we demonstrate that the structure of this polymer is different. Solid molecular CS 2 polymerizes at ∼10-11 GPa. The polymer is disordered and consists of a mixture of 3-fold (C3) and 4-fold (C4) coordinated carbon atoms with some C═C double bonds. The C4/C3 ratio continuously increases upon further compression to 40 GPa. Upon decompression, structural changes are partially reverted, while the sample also undergoes partial disproportionation. Our work uncovers the nontrivial high-pressure structural evolution in one of the simplest molecular systems exhibiting molecular as well as polymeric phases.

Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be harnessed for the targeted delivery of neuroprotective agents. Ischemic tissue acidosis, which represents the accumulation of lactic acid in malperfused brain tissue is significantly exacerbated by the recurrence of spreading depolarizations. Deepening acidosis itself activates specific ion channels to cause neurotoxic cellular Ca 2+ accumulation and cytotoxic edema. These processes are thought to contribute to the loss of the ischemic penumbra. The unique metabolic status of the ischemic penumbra has been exploited to identify the penumbra zone with imaging tools. Importantly, acidosis in the ischemic penumbra may also be used to guide therapeutic intervention. Agents with neuroprotective promise are suggested here to be delivered selectively to the ischemic penumbra with pH-responsive smart nanosystems. The administered nanoparticels release their cargo in acidic tissue environment, which reliably delineates sites at risk of injury. Therefore, tissue pH-targeted drug delivery is expected to enrich sites of ongoing injury with the therapeutical agent, without the risk of unfavorable off-target effects.

We report here the pressure-induced amorphization and reversible structural transformation between two amorphous forms of SO 2 : molecular amorphous and polymeric amorphous, with the transition found at 26 GPa over a broad temperature regime, 77 K to 300 K. The transformation was observed by both Raman spectroscopy and X-ray diffraction in a diamond anvil cell. The results were corroborated by ab initio molecular dynamics simulations, where both forward and reverse transitions were detected, opening a window to detailed analysis of the respective local structures. The high-pressure polymeric amorphous form was found to consist mainly of disordered polymeric chains made of three-coordinated sulfur atoms connected via oxygen atoms, with few residual intact molecules. This study provides an example of polyamorphism in a system consisting of simple molecules with multiple bonds., Competing Interests: The authors declare no competing interest.

Spontaneous, recurrent spreading depolarizations (SD) are increasingly more appreciated as a pathomechanism behind ischemic brain injuries. Although the prostaglandin F2α - FP receptor signaling pathway has been proposed to contribute to neurodegeneration, it has remained unexplored whether FP receptors are implicated in SD or the coupled cerebral blood flow (CBF) response. We set out here to test the hypothesis that FP receptor blockade may achieve neuroprotection by the inhibition of SD. Global forebrain ischemia/reperfusion was induced in anesthetized rats by the bilateral occlusion and later release of the common carotid arteries. An FP receptor antagonist (AL-8810; 1 mg/bwkg) or its vehicle were administered via the femoral vein 10 min later. Two open craniotomies on the right parietal bone served the elicitation of SD with 1 M KCl, and the acquisition of local field potential. CBF was monitored with laser speckle contrast imaging over the thinned parietal bone. Apoptosis and microglia activation, as well as FP receptor localization were evaluated with immunohistochemistry. The data demonstrate that the antagonism of FP receptors suppressed SD in the ischemic rat cerebral cortex and reduced the duration of recurrent SDs by facilitating repolarization. In parallel, FP receptor antagonism improved perfusion in the ischemic cerebral cortex, and attenuated hypoemic CBF responses associated with SD. Further, FP receptor antagonism appeared to restrain apoptotic cell death related to SD recurrence. In summary, the antagonism of FP receptors (located at the neuro-vascular unit, neurons, astrocytes and microglia) emerges as a promising approach to inhibit the evolution of SDs in cerebral ischemia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

Immune status was investigated in 186 patients with chronic lymphoid leukaemia between January 2012 and March 2015. Incidences of infections and mortality were analysed in patients who did not receive prophylactic immunoglobulin therapy. Immunoglobulin G (IgG) levels were normal (7-17.8 g/L) or decreased in 62.37% and 35.48% of patients, respectively. We measured high immunoglobulin levels only in a few cases (2.15%). Immunoglobulin levels became increasingly lower in more advanced disease stages (Rai stages). The number of infections was inversely proportional to that. Hypogammaglobulinaemia proved to be more important than disease progression in terms of the development of infections. The most common infections were upper respiratory tract (33.07%) and sepsis (18.90%). Two months after chemotherapy, initially normal immunoglobulin levels decreased by an average of 21%, and at the same time the incidence of infections increased. The most common cause of death was sepsis: 30% occurred at low immunoglobulin levels, while 20% at normal immunoglobulin levels. According to literature, prophylactic immunoglobulin treatment is indicated in patients with chronic lymphoid leukaemia and immunodeficiency for decreasing both morbidity and mortality. According to recommendations in literature, replacement treatment must be administered in severe or moderately severe recurrent bacterial infections. Immunoglobulin prophylaxis may be provided as low dose (10 g), fix dose (18 g) or individually customized higher dose (300-400 mg/kg body weight) treatment. According to recommendations, higher dose immunoglobulin prophylaxis, administered every three weeks on six occasions, is more efficient when customized. With this dose, infection-free condition may be achieved in 50% of patients. Orv Hetil. 2019; 160(38): 1487-1494.

Background and Purpose: A new class of dihydropyridine derivatives, which act as co-inducers of heat shock protein but are devoid of calcium channel antagonist and vasodilator effects, has recently been developed with the purpose of selectively targeting neurodegeneration. Here, we evaluated the action of one of these novel compounds LA1011 on neurovascular coupling in the ischaemic rat cerebral cortex. As a reference, we applied nimodipine, a vasodilator dihydropyridine and well-known calcium channel antagonist., Experimental Approach: Rats were treated with LA1011 or nimodipine, either by chronic, systemic (LA1011), or acute, local administration (LA1011 and nimodipine). In the latter treatment group, global forebrain ischaemia was induced in half of the animals by bilateral common carotid artery occlusion under isoflurane anaesthesia. Functional hyperaemia in the somatosensory cortex was created by mechanical stimulation of the contralateral whisker pad under α-chloralose anaesthesia. Spreading depolarization (SD) events were elicited subsequently by 1 M KCl. Local field potential and cerebral blood flow (CBF) in the parietal somatosensory cortex were monitored by electrophysiology and laser Doppler flowmetry., Key Results: LA1011 did not alter CBF, but intensified SD, presumably indicating the co-induction of heat shock proteins, and, perhaps an anti-inflammatory effect. Nimodipine attenuated evoked potentials and SD. In addition to the elevation of baseline CBF, nimodipine augmented hyperaemia in response to both somatosensory stimulation and SD, particularly under ischaemia., Conclusions and Implications: In contrast to the CBF improvement achieved with nimodipine, LA1011 seems not to have discernible cerebrovascular effects but may up-regulate the stress response., (© 2019 The British Pharmacological Society.)

: The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions. Detected with conventional laboratory tests high-risk thrombophilia was present in 70 patients: deficiencies of antithrombin (AT) (n = 12), protein C (PC) (n = 14), protein S (PS) (n = 6), homozygous factor V Leiden (FVL) mutation (n = 9) and combined types (n = 29). Low-risk thrombophilia was present in 123 patients: heterozygous FVL (n = 115) and FII G2010A mutation (n = 8). Significantly lower median CIP values were found for AT-,PC-, PS deficiencies, homozygous and heterozygous FVL mutations and combined thrombophilias (P < 0.01) as compared with healthy controls. There was no significant difference between the heterozygous FIIG20210A (P = 0.669) thrombophilia group and the healthy controls. The best performance of the test was achieved at the cut-off value of 90.0 U (area: 0.981) with 96% sensitivity and 92% specificity in the high-risk thrombophilia group estimated by receiver operating characteristic analysis. The new method seems to be appropriate and reliable for the detection of AT-, PC- and PS deficiencies, homozygous FVL mutation and also for combined deficiencies. The automated CIP test is insensitive to FII G2010A mutation.

T-cell lymphoma is a poor prognostic hematological malignancy. The generally used - not sufficiently effective - induction chemotherapy should be improved with consolidative autologous hemopoetic stem cell transplantation. The authors describe the role, place and effectiveness of transplantation in this disorder. One hundred thirty three autologous stem cell transplantations were performed in the last 22 years in Hungary. Detailed results are available from the last 6 years. In this period 43 transplantations were carried out in 4 Hungarian centers. Carmustine-etoposide-cytosine arabinoside-melphalan (BEAM) conditioning regimen was used in 95%. The transplantation was done mainly in complete remission (84%), 1 year after transplantation 65% of patients were still in complete remission. Eleven patients died, 82% of them have progressive disease. Brentuximab vedotin has already proved the effectiveness, several other chemoterapeutics, monoclonal antibodies, kinase inhibitors are under investigation. In certain cases allogeneic stem cell transplantation has real indication among therapeutic options. Orv Hetil. 2017; 158(41): 1615-1619.

Introduction: Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. The aim of the study was to follow the changes of haemostatic parameters and to establish gestational age-specific reference intervals during normal pregnancy., Materials and Methods: Blood samples of 83 pregnant women were collected at gestational weeks 16, 26 and 36. Fibrinogen, D-dimer, and C-Reactive Protein (CRP) were examined. Reference intervals were calculated for fibrinogen, D-dimer tests with two different methods (mean±2 SD or median and 2.5th and 97.5th percentiles with 90% confidence intervals)., Results: fibrinogen and D-dimer increased progressively throughout pregnancy. Mean fibrinogen levels were higher than the maximum of the conventional reference interval, already in the 16th week of pregnancy. D-dimer levels were at or above the conventional cutoff point (250ng/mL) throughout the pregnancy in 42% of pregnant women, while in the 36th week 98% of them displayed elevated D-dimer levels. CRP did not increase in normal pregnancy., Conclusions: There seems to be an emerging need to reconsider fibrinogen and D-dimer values from a different aspect in pregnancy compared to non-pregnant reference intervals. New reference ranges are suggested to be established in pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Several methods are used to analyse platelet function in whole blood. A new device to measure whole blood platelet aggregation has been developed, called multiple electrode platelet aggregometry (MEA). Our aim was to evaluate MEA in comparison with the single platelet counting (SPC) method for the measurement of platelet aggregation and platelet inhibition by aspirin or apyrase in diluted whole blood. Platelet aggregation induced by different concentrations of ADP, collagen and TRAP-6 and platelet inhibition by apyrase or aspirin were determined in citrateor hirudin-anticoagulated blood by MEA and SPC. MEA indicated that spontaneous platelet aggregation was lower, and stimulated platelet aggregation was higher in hirudin- than citrate-anticoagulated blood. In hirudin-anticoagulated, but not citrate-anticoagulated blood, spontaneous platelet aggregation measured by MEA was inhibited by apyrase. For MEA compared with SPC the dose response-curves of agonist-induced platelet aggregation in citrate- and hirudin-blood showed similar EC50 values for TRAP, and higher EC50 values for ADP (non-significant) and collagen (p < 0.05). MEA and the SPC method gave similar results concerning platelet-inhibition by apyrase and aspirin. MEA was more sensitive than SPC to the inhibitory effect of aspirin in collagen-induced aggregation. In conclusion, MEA is an easy, reproducible and sensitive method for measuring spontaneous and stimulated platelet aggregation, and evaluating antiplatelet drugs in diluted whole blood. The use of hirudin as an anticoagulant is preferable to the use of citrate. MEA is a promising technique for experimental and clinical applications.

It has been shown that PARP inhibition is protective in several models of ischemia-reperfusion injury including cardiac, cerebral and renal ones. Due to their ability to reduce myocardial necrosis and to improve myocardial function PARP inhibitors emerged as candidates for treating various cardiovascular diseases including acute myocardial ischemia. Since the pathophysiology of acute ischemic cardiac diseases involves haemostatic impairment and the therapeutic regimen includes antithrombotic drugs, we investigated the effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with platelet aggregation inhibitors (aspirin, eptifibatide and tirofiban), unfractionated heparin, low molecular weight heparin (enoxaparin) or the recombinant fibrinolytic drug (alteplase), on various haemostatic parameters in vitro. ADP- and epinephrine-induced platelet aggregation was evaluated by optical aggregometry in the presence or absence of different concentrations of INO-1001, in combination with aspirin, tirofiban, eptifibatide or saline on ten healthy volunteers' platelet rich plasma (PRP). Activated partial thromboplastin time, Anti-Xa activity and euglobulin lysis time were determined in the presence or absence of different concentrations of INO-1001, in combination with sodium heparin, enoxaparin or alteplase, respectively. INO-1001, on its own does not affect the measured platelet, and haemostatic functions, i.e. does not reduce the respective anti-platelet, anti-coagulant and thrombolytic activity of therapeutically relevant concentrations of aspirin, tirofiban, eptifibatide, enoxaparin and alteplase in vitro. INO-1001 enhanced the effects of heparins above therapeutic ranges; the magnitude of this effect was negligible. Consequently, the PARP inhibitor INO-1001 can be safely applied together with the drugs tested.

Introduction: In rare cases of thromboembolic diseases developing in young age, venous and arterial thromboembolism can occur simultaneously., Aims: To detect the venous and the arterial risk factors in a severe thrombophilic family. A 47-years-old female with severe atherosclerosis and recurrent deep vein thrombosis, and 6 members of her family were analysed., Methods: The following haemostatic and molecular genetic investigations were performed: besides the rutin haemostatic parameters, risk factors for venous thrombembolic disease, risk factors for venous and arterial thrombosis (plasma homocysteine level, MTHFR C677T polymorphism) were determined. This panel was completed with the measurement of lipoprotein (a), von Willebrand factor, plasminogen activator inhibitor-1 antigen, serum total cholesterin, HDL cholesterin, C reactive protein and PIA2 variant. The propositus was proven to have type I antithrombin deficiency, elevated homocysteine level, homozygous MTHFR C677T polymorphism, elevated Lp(a), vWF:Ag, and PAI-1:Ag levels., Results: All family members had a combination of cardiovascular risk factors (in 4 cases elevated homocysteine level, in 3 cases elevated Lp(a), in 2 cases elevated vWF:Ag, in 4 cases increased PAI-1 level). These risk factors were combined in three cases with type I antithrombin deficiency. Despite of the presence of atherosclerotic risk factors in the family, arterial thrombotic disease could be detected only in two patients with antithrombin deficiency., Conclusions: The results of the investigated family indicate that in case of combination of venous and arterial thromboembolic risk factors, antithrombin deficiency may contribute to the manifestation of arterial thromboembolic diseases.

Objective: To evaluate our first experience with thermal balloon therapy of abnormal uterine bleeding., Design: Prospective study., Setting: Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University, Prague., Methods: Ten procedures of balloon thermal endometrial ablations were performed between November 1998 and February 1999. From ten patients with abnormal uterine bleeding, 4 patients with concomitant polymorbidity (sclerosis multiplex, hypertension, hepatopathia, pyelonephritis) where more invasive intervention was not recommended or was contraindicated. Treatment entailed controlled heating of intrauterine balloon. Local anaesthesia-paracervical block with analgosedation was employed in 50% of procedures and general anaesthesia was employed in 50% of cases. Follow up after 3, 6, 12, 24 months is required. Success was defined as the reduction of menses to eumenorrhoea or less., Results: Preliminary results after 6 months follow up are successful in 100%; in 5 (50%) cases we recorded amenorrhoea, in 2 (20%) cases hypomenorrhoea and in 3 (30%) cases eumenorrhoea., Conclusion: Thermal balloon endometrial ablation appears to be safe due to its minimal invasivity especially in patients with abnormal uterine bleeding with concomitant polymorbidity.