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Despite numerous studies on cerebrospinal fluid (CSF) and its importance during hydrocephalus or myelography, no reliable values exist about its overall volume in dogs. In this study, our aim was to measure the intracranial (IC) volume of CSF in dogs and assess its possible relationship with body size and the symmetry of the lateral ventricles. We ran a 3D magnetic resonance imaging (MRI) sequence on the central nervous system of 12 healthy, male mongrel dogs between 3-5 years of age and 7.5-35.0 kg body weight. A validated semiautomatic segmentation protocol was implemented to segment the CSF and measure its volume. Values for the volume of the ventricular compartment were between 0.97 and 2.94 ml, with 62.1 ± 11.7% in the lateral ventricles, 17.6 ± 4.9% in the third ventricle, 4.9 ± 1.6% in the aqueductus mesencephali and 15.5 ± 6.6% in the fourth ventricle. In 11 cases a significant asymmetry was found between the lateral ventricles. The results suggest that it may be normal for a dog to have one of the lateral ventricles 1.5 times larger than the other. The correlation between body weight and CSF volume was linear, indicating that the current dosage protocols for myelography, based on a hypothetical proportional relationship with body weight, may have to be revised.

Consumption of high-energy diets may compromise health and may also impair cognition; these impairments have been linked to tasks that require hippocampal function. Conversely, food restriction has been shown to improve certain aspects of hippocampal function, including spatial memory and memory persistence. These diet-dependent functional changes raise the possibility that the synaptic structure underlying hippocampal function is also affected. To examine how short-term food restriction (FR) alters the synaptic structure of the hippocampus, we used quantitative electron microscopy to analyze the organization of neuropil in the CA1 stratum radiatum of the hippocampus in young rats, consequent to reduced food. While four weeks of FR did not modify the density, size, or shape of postsynaptic spines, the synapses established by these spines were altered, displaying increased mean length, and more frequent perforations of postsynaptic densities. That the number of perforated synapses (believed to be an indicator of synaptic enhancement) increased, and that the CA1 spine population had on average significantly longer PSDs suggests that synaptic efficacy of axospinous synapses also increased in the CA1. Taken together, our ultrastructural data reveal previously unrecognized structural changes at hippocampal synapses as a function of food restriction, supporting a link between metabolic balance and synaptic plasticity., (© 2015 Wiley Periodicals, Inc.)

We present here a new procedure to represent the 3D distribution of neuronal cell bodies within the brain, using exclusively softwares free for research purposes. Our technique is based on digitalized photos of brain slices processed by immunohistochemical technique, and the 3D Slicer software. The technique presented enables transposition of immunohistochemical or in situ hybridization data to the stereotaxic mouse brain atlas (e.g. Paxinos, G., Franklin, K.B.J., 2001. The Mouse Brain in Stereotaxic Coordinates. second ed. Academic Press, San Diego). By exporting the finalized models into a popular 3D design software (3DS Max) arbitrary environment and motion simulation can be created to improve the visual understanding of the area studied. Application of this technique provides the possibility to store, analyze and compare data - e.g. on the hypothalamic neuropeptides - across experimental techniques and laboratories. The method is exemplified by visualizing the distribution of immunohistochemically identified melanin-concetrating hormone (MCH) containing perikarya within the mouse hypothalamus., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2)  ≥ 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration., (Copyright © 2015 John Wiley & Sons, Ltd.)

Dosages for myelography procedures in dogs are based on a hypothetical proportional relationship between bodyweight and cerebrospinal fluid (CSF) volume. Anecdotal radiographic evidence and recent studies have challenged the existence of such a defined relationship in dogs. The objectives of this prospective cross-sectional study were to describe CSF volumes using magnetic resonance imaging (MRI) in a group of clinically healthy dogs, measure the accuracy of MRI CSF volumes, and compare MRI CSF volumes with dog physical measurements. A sampling perfection with application optimized contrast using different flip-angle evolution MRI examination of the central nervous system was carried out on 12 healthy, male mongrel dogs, aged between 3 and 5 years with a bodyweight range of 7.5-35.0 kg. The images were processed with image analysis freeware (3D Slicer) in order to calculate the volume of extracranial CSF. Cylindrical phantoms of known volume were included in scans and used to calculate accuracy of MRI volume estimates. The accuracy of MRI volume estimates was 99.8%. Extracranial compartment CSF volumes ranged from 20.21 to 44.06 ml. Overall volume of the extracranial CSF increased linearly with bodyweight, but the proportional volume (ml/bodyweight kilograms) of the extracranial CSF was inversely proportional to bodyweight. Relative ratios of volumes in the cervical, thoracic, and lumbosacral regions were constant. Findings indicated that the current standard method of using body weight to calculate dosages of myelographic contrast agents in dogs may need to be revised., (© 2015 American College of Veterinary Radiology.)

We aim to introduce a novel, inverse method for in vivo material parameter identification of human abdominal aortic aneurysms (AAA), which could overcome one of the greatest sources of uncertainty in patient-specific simulations, and could also serve as a rapid, patient-calibrated, novel measure of aneurysm rupture risk. As an initial step, the determination of the kinematic fields is presented here. Images of the AAA lumen, acquired in 10 discrete time-steps through a stabilized cardiac cycle by electrocardiogram-gated computer tomography angiography, are used to approximate the in vivo, time dependent kinematic fields of the arterial wall using a novel, incompressible Kirchhoff-Love shell element implemented into the isogeometric analysis framework. Defining a smoothing parametric surface via 2D bicubic spline fitting in the spatial, and by harmonic regression in the temporal domain, we are able to adequately mitigate the measurement inaccuracy. The ill-posedness of the problem requires certain assumptions on the displacement. In our case, based on numerical fluid structure interaction simulation observations, we hypothesized the incremental displacement vector of the reference surface to coincide with its corrected normal; hence the periodic movement was assured. Finally, we present two examples: an AAA and an undilated calcificated aorta. Strains in the diseased part were compared to those in a healthy arterial section of the same patient and found to have significant differences in both specimens. In the case of AAAs, high spatial gradients surrounding the dilated part indicate abrupt changes in material properties, a phenomenon less significant for the atherosclerotic case., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Case Report: The first case was a 77-year-old man with 5.6 cm juxtarenal abdominal aortic aneurysm who presented with multiple comorbidities. The patient had a single left kidney. A custom-made, single fenestrated stent graft was implanted successfully. The one-month follow-up showed a patent left renal fenestration without evidence of any endoleaks. Four months after the operation the patient was admitted with acute uremia. Imaging studies revealed an occluded left renal stent, which was successfully reopened. The second case was a 71-year-old man with 8.0 cm juxtarenal aneurysm. He presented with severe coronary artery disease among other multiple comorbidities in his medical history. He was successfully treated with a 3-vessel custom-made fenestrated stent graft to the renal and the superior mesenteric arteries. The one-month CT imaging revealed patent fenestrations without endoleaks., Discussion: With the development of fenestrated endograft technology, complex aneurysms with visceral artery involvement can be treated with complete endovascular approaches. The first fenestrated endovascular case in Hungary was treated in the Heart and Vascular Center of Semmelweis University, Budapest. The short and middle-term results are offering improved clinical results when compared with conventional surgery, but the long-term outcomes are difficult to ascertain from the current published series.

Introduction: Fibrin structure and cellular composition of thrombi profoundly affect the clinical outcomes in ischemic coronary and peripheral artery disease. Our study addressed the interrelations of structural features of thrombi and routinely measured laboratory parameters., Materials and Methods: Thrombi removed by thromboaspiration following acute myocardial infarction (n=101) or thrombendarterectomy of peripheral arteries (n=50) were processed by scanning electron microscopy and immunostaining for fibrin and platelet antigen GPIIb/IIIa to determine fibrin fibre diameter and relative occupancy by fibrin and cells. Correlations between the structural characteristics and selected clinical parameters (age, sex, vascular localization, blood cell counts, ECG findings, antiplatelet medication, accompanying diseases, smoking) were assessed., Results: We observed significant differences in mean fibre diameter (122 vs. 135 nm), fibrin content (70.5% vs. 83.9%), fluorescent fibrin/platelet coverage ratio (0.18 vs. 1.06) between coronary and peripheral thrombi. Coronary thrombi from smokers contained more fibrin than non-smokers (78.1% vs. 62.2% mean occupancy). In the initial 24 h, fibrin content of coronary thrombi decreased with time, whereas in peripheral thrombi platelet content increased in the first 7 days. In coronaries, higher platelet content and smaller vessel diameter were associated with thinner fibrin fibres, whereas hematocrit higher than 0.35 correlated with larger intrathrombotic platelet occupancy. Smoking and dyslipidaemia strengthened the dependence of clot platelet content on systemic platelet count (the adjusted determination coefficient increased from 0.33 to 0.43 and 0.65, respectively)., Conclusion: Easily accessible clinical parameters could be identified as significant determinants of ultrastructure and composition of coronary and peripheral thrombi., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: Recent evidences show correlations between atherosclerosis and the serum level of third component of complement (C3). However, there is less data on the connection of C3 and the severity of atherosclerosis. The aim of our study was to evaluate the association of serum C3 levels with atherosclerosis and arterial calcification in patients with chronic lower extremity atherosclerosis., Methods: In a single centre cross-sectional study 103 patients and 109 healthy controls were examined. Sera were analyzed for C3. To identify the severity of atherosclerosis and calcification, ankle-brachial Doppler index, angiographic Bollinger score, arterial calcification score and carotid intima-media thickness was determined., Results: Serum level of C3 was significantly higher in the lower extremity atherosclerosis group than in healthy patients (P=0.00004). In the patient group, serum level of C3, C4 was significantly and inversely associated with ABI (r=-0.246, P=0.014), (r=-0.259, P=0.011). C3 inversely correlates with Bollinger score (r= -0.357, P=0.028). Among our patients no correlation was found between C3 levels and CS (P=0.672, r=-0.046) or between C3 levels and carotid IMT (r=0.104, P=0.351). The serum levels of different complement components were associated with C-reactive protein, Hba1c, peptide-C and insulin., Conclusion: Our results suggest that C3 serum levels are associated with ABI and angiographic parameters of atherosclerosis, but do not relate to the severity of calcification.

By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.

Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nM dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator.

Case Report: We present a case of a 53 year old male renal transplanted patient, who presented with severe dyspnea. Chest X-ray and CT angiography showed a left sided haemothorax caused by an aortic arch aneurysm rupture. Acute operation was carried out, an ascendo-anonymo-carotid "Y" bypass was performed from sternotomy and a stent graft implantation through femoral artery. As a second step, the blood clot mass, which caused compression atelectasis of the left lung, was removed by a thoracic surgeon. At follow-up the patient was in good condition, the bypass graft functioned well, the stent graft stayed in good position, the aneurysm sack was reduced and the left lung expanded well., Discussion: Traditional operation of aortic arch aneurysm carries high mortality and morbidity rate, because of use of extracorporeal perfusion and deep hypothermic circulatory arrest. Hybrid operation became an alternative treatment. After circulation of supra-aortic arteries secured by "debranching procedure", a stent graft implantation is done. Such interventions means less strain for patients, but strict follow up is required, because lack of long-term data. Hybrid reconstruction of the aortic arch aneurysm is rarely performed in acute cases, but means an alternative treatment for high risk patients with acceptable results.

Decarboxylation, reduction and hydrolysis can yield active metabolites from the parent drug. Major therapeutic indications and metabolic routes of these drugs are reviewed. Changes in the logP values (determined and calculated) from the parent drug to the active metabolite show certain characteristics in comparison to other phase I metabolic alterations. Metabolic decarboxylation of parent drug is commonly associated with increase in lipophilicity. However, in some cases, decarboxylation may cause a reduction in lipophilicity. Ester hydrolysis generally unmasks either the polar carboxylic or hydroxyl group with the outcome of an increase in hydrophilicity. On the contrary, hydrolysis of phosphate ester means a huge increase in the lipophilic character of the drug, as the highly polar phosphate group is removed.

Objective: Arterial thrombi contain variable amounts of red blood cells (RBCs), which interact with fibrinogen through an eptifibatide-sensitive receptor and modify the structure of fibrin. In this study, we evaluated the modulator role of RBCs in the lytic susceptibility of fibrin., Methods and Results: If fibrin is formed at increasing RBC counts, scanning electron microscopy evidenced a decrease in fiber diameter from 150 to 96 nm at 40% (v/v) RBCs, an effect susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBCs prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue plasminogen activator (tPA) by up to 22.7±1.6%, but not in the presence of eptifibatide. Confocal laser microscopy using green fluorescent protein-labeled tPA and orange fluorescent fibrin showed that 20% to 40% (v/v) RBCs significantly slowed down the dissolution of the clots. The fluorescent tPA variant did not accumulate on the surface of fibrin containing RBCs at any cell count above 10%. The presence of RBCs in the clot suppressed the tPA-induced plasminogen activation, resulting in 45% less plasmin generated after 30 minutes of activation at 40% (v/v) RBCs., Conclusions: RBCs confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC interactions.

Background: Clinical studies are limited regarding the role of human nociceptin/orphanin FQ (N/OFQ) in ischemic cardiovascular diseases, which are still the number one cause of death in the developed world. The aim of our study was to measure the plasma levels of N/OFQ in patients with chronic ischemic cardiovascular diseases in a pilot study., Methods and Results: Our study population consisted of 22 patients presenting symptoms of stable angina pectoris (SAP): 12 severe Canadian Cardiovascular Society (CCS) III-IV functional class, and 10 with milder SAP (CCS II-III). 12 patients were also enrolled with chronic peripheral artery disease (9 with intermittent claudication; 3 with rest pain and gangrene). Patients were asked to avoid any exertion or given analgetics for their rest pain. Patients had no episodes of chest or limb pain in 1week before their fasting blood samples were taken and N/OFQ plasma levels were measured by radioimmunoassay. 14 healthy subjects without any cardiac risk factors served as a control group., Conclusions: N/OFQ levels were significantly lower in patient groups with severe vs. milder chronic angina (p<0.05) and vs. control subjects (p<0.01). Patients suffering from peripheral artery disease had also a lower plasma N/OFQ levels than in healthy controls (p<0.01). Our findings show that chronic ischemic conditions of atherosclerotic origin are associated with significantly lower plasma N/OFQ levels., (Copyright © 2011 Elsevier B.V. All rights reserved.)

After the First World War the professional medical societies in Hungary, which have already organized themselves nationwide, started to operate independently from each other. In that time came the idea to create another association above the others to gather them together while retaining their independent functioning. The Association of the Scientific Societies of Hungarian Medical Doctors (MORTESZ), established in 1931, became the nationwide forum for many medical associations. It also organized the first Hungarian Medical Grand-Week which became the annual meeting of the medical society. In the first year the cooperation only consisted of a common topic of two or three associations presented in the "Grand-Week". From year 1935, reports were appointed annually that each professional association could comment on. The proceedings of the "Grand-Week" were published yearly as appendices of the Hungarian Medical Journal. After the Second World War the activities of the independent associations were shut down by the authorities. The scientific and professional associations could continue their work as sections inside of the Doctors and Health Workers' Union. In 1966 the situation was solved thanks to the initiative of the Trade Union, the Department of Medicine and the Medical Section of the Hungarian Academy of Sciences which resulted in the foundation of the Association of the Hungarian Medical Societies (MOTESZ) which continues to gather together the collective work of many scientific associations and carries out tasks of general interest since then, similarly to the now 80-years-old MORTESZ.

Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.

Background: The pathway from viral myocarditis to end-stage heart failure is commonly accepted, but diagnosis of virus-mediated myocardial injury remains challenging. Virus persistency in the myocardium may accelerate ventricular failure; thus, a precise diagnosis of virus persistency may prevent the development of end-stage heart failure., Methods: We performed a systematic investigation on the sampling error of viral diagnostics in heart transplant recipients: Transmural samples from 5 regions of the explanted hearts from recipients during heart transplantation were amplified using entero-, adeno-, and herpesvirus sequences and histologic examinations performed., Results: We examined 175 myocardial samples from dilated cardiomyopathy and 100 samples from 20 forensic medicine patients. Seven patients were positive for the examined viruses: 10 positive regions for adenovirus, and 1 positive region for herpes virus DNA, but none for enterovirus. A focal myocardial pattern was detected for adenovirus., Conclusion: Our results with the patchy myocardial viral persistence may explain possible false-negative results related to virus-mediated etiology among end-stage dilated cardiomyopathy patients. Therefore, repeated endomyocardal biopsies, and multiple cardiac samples are recommended to be obtained to evaluate the etiology of heart failure, thus reducing the occurrence of end-stage heart failure and decreasing the number of patients requiring heart transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer's kits. Fetuin-a levels were measured by radial immunodiffusion. Patients' median age was 64 (57-71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156-4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021-5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.

Background: Recent data indicate that stretching forces cause a dramatic decrease in clot volume accompanied by gross conformational changes of fibrin structure., Objective: The present study attempts to characterize the lytic susceptibility of fibrin exposed to mechanical stress as a model for fibrin structures observed in vivo., Methods and Results: The relevance of stretched fibrin models was substantiated by scanning electron microscopic (SEM) evaluation of human thrombi removed during surgery, where surface fibrin fibers were observed to be oriented in the direction of shear forces, whereas interior fibers formed a random spatial meshwork. These structural variations were modeled in vitro with fibrin exposed to adjustable mechanical stress. After two- and three-fold longitudinal stretching (2 × S, 3 × S) the median fiber diameter and pore area in SEM images of fibrin decreased two- to three-fold. Application of tissue plasminogen activator (tPA) to the surface of model clots, which contained plasminogen, resulted in plasmin generation which was measured in the fluid phase. After 30-min activation 12.6 ± 0.46 pmol mm(-2) plasmin was released from the non-stretched clot (NS), 5.5 ± 1.11 pmol mm(-2) from 2 × S and 2.3 ± 0.36 pmol mm(-2) from 3 × S clot and this hampered plasmin generation was accompanied by decreased release of fibrin degradation products from stretched fibrins. Confocal microscopic images showed that a green fluorescent protein-fusion variant of tPA accumulated in the superficial layer of NS, but not in stretched fibrin., Conclusion: Mechanical stress confers proteolytic resistance to fibrin, which is a result of impaired plasminogen activation coupled to lower plasmin sensitivity of the denser fibrin network., (© 2011 International Society on Thrombosis and Haemostasis.)

The mechanisms leading to death from anaphylaxis after insect sting involve antigen cross-linkage of antibody molecules that activate immunoglobulin receptors on inflammatory cells. The aim of our study was to investigate the pathomorphology and the expression of C5aR in fatal anaphylaxis in a patient after a fatal insect sting. A 38-year-old women was stung by a honeybee. C5R1 expression was detected in many dilated capillaries in the lungs. Pulmonary epithelial cells did not bind the monoclonal antibody for C5R1; however, intensive cytoplasmic staining was detected in endothelial cells. The findings of this case provide evidence for an active role of complement in fatal anaphylaxis elicited by bee venom. C5aR detection could be useful in the identification of sudden death cases because of unwitnessed fatal insect sting cases. Authors can recommend this immunohistochemical analysis on all sudden unexpected deaths outdoors where a possible bee sting might occur., (© 2011 American Academy of Forensic Sciences.)

Background: Fetuin-A is a glycoprotein that inhibits extraosseous and vascular calcification. Its serum level is lower in patients with atherosclerosis compared with healthy controls, but its role is unknown in aneurysmal diseases. The aim of our study was to investigate the association of serum fetuin-A levels with aortic aneurysms of different aetiology: Marfan syndrome and atherosclerosis., Material and Methods: In a single centre cross-sectional observational study, 105 patients (30 with atherosclerotic aortic aneurysm, 15 with Marfan syndrome, 30 with peripheral arterial disease and 30 healthy controls) were examined; sera were analysed for fetuin-A, standard markers of possible inflammation, lipid profile, kidney and hepatic disease and diabetes. Systemic atherosclerosis was assessed by carotid intima-media thickness (IMT) measurement and arterial calcification score of cardiac valves, carotids, aorta and femoral arteries determined by ultrasound., Results: Serum fetuin-A levels (median and IQR) were significantly lower in the atherosclerotic aneurysm cohort than in patients with Marfan syndrome: 708 μg mL⁻¹ (612-780) and 756 μg mL⁻¹ (708-816), respectively, (P = 0·0428). Fetuin-A levels were 754 μg mL⁻¹ (713-777) in the control group and 654 μg mL⁻¹ (600-756) in patients with peripheral arterial disease. Mean and maximum IMT, ACS values and homocysteine levels were significantly higher in patients with atherosclerosis: P < 0·0001, P < 0·0001, P < 0·0001 and P = 0·0034, respectively. There was no significant difference between aneurysm groups analysing the results of lipid profile and acute-phase markers., Conclusions: The significantly lower serum level of fetuin-A in the atherosclerotic aneurysm group supports the protective role of fetuin-A in the evolution of arterial calcification., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Therapeutic use of hypothermia has come to the frontline in the past decade again in the prevention and in mitigation of neurologic impairment. The application of hypothermia is considered as a successful therapeutic measure not just in neuro- or cardiac surgery, but also in states causing brain injury or damage. According to our present knowledge this is the only proven therapeutic tool, which improves the neurologic outcome after cardiac arrest, decreasing the oxygen demand of the brain. Besides influencing the nervous system, hypothermia influences the function of the whole organ system. Beside its beneficial effects, it has many side-effects, which may be harmful to the patient. Before using it for a therapeutic purpose, it is very important to be familiar with the physiology and complications of hypothermia, to know, how to prevent and treat its side-effects. The purpose of this article is to summarize the physiologic and pathophysiologic effects of hypothermia.

Leukocytes invade newly formed thrombi through interactions with platelets and fibrin and later contribute to the removal of fibrin deposits mainly through the action of neutrophil elastase. The present study attempts to express in quantitative terms the impact of neutrophils on the lytic processes in obliterative thrombi based on the local presence of elastase-specific fibrin degradation products (NE-FDP) in relation to the leukocyte, platelet and fibrin content of thrombi. Immunofluorescent detection of fibrin, NE-FDP and platelet antigens was performed in sections of thrombi from 28 patients subjected to thrombectomy in combination with DNA-staining for identification of nucleated cells. The digitalized fluorescent microscopic images were decomposed according to the color channel of each thrombus constituent. The integrated intensity values for all thrombus constituents were statistically evaluated with correlation, hierarchical agglomerative clustering , Hotelling'sT(2) and F-statistics. Association between NE-FDP and leukocyte content of thrombi is evidenced by a significant Pearson correlation coefficient of 0.71 (p=0.00002). Cluster analysis reveals two classes of thrombi according to NE-FDP, leukocyte and platelet content and also two according to NE-FDP, leukocyte and fibrin content. When NE-FDP, fibrin and platelet content is normalized to the leukocyte count in the same thrombus, clusters with platelet-related thrombolytic resistance (inversely related NE-FDP and platelet content) and advanced cell-dependent thrombolysis (inversely related NE-FDP and fibrin content) are identified. These distinct patterns of thrombus constituents are snapshots of characteristic stages in the cell-dependent thrombolysis, which indicate a clot-stabilizing role for platelets in this process similar to their impact on the plasmin-dependent lysis., ((c) 2010 Elsevier Ltd. All rights reserved.)

Summary Background: Under high shear stress platelets adhere preferentially to the adventitia layer of the arterial vessel wall in a von Willebrand factor (VWF)-dependent manner., Objective: The present study was undertaken in an attempt to characterize the structural background of the relative thromboresistance of the media and the impact of neutrophil leukocyte-derived proteases (matrix metalloproteinases, neutrophil elastase) on platelet adhesion in this layer of the arteries., Methods and Results: Platelet adhesion to cross-sections of the human iliac artery was monitored by indirect immunofluorescent detection of GpIIb/IIIa antigen. Exposure of the vessel wall to activated neutrophils or neutrophil-derived proteases increased platelet adhesion to the media about tenfold over the control level at 3350 s(-1) surface shear rate. In parallel with this enhanced thrombogenicity morphological changes in the media were evidenced by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The fine proteoglycan meshwork seen with Cupromeronic Blue enhancement of the SEM images was removed by the proteolytic treatment and the typical collagen fiber structure was exposed on the AFM images of the media., Conclusion: Through their proteases activated neutrophils degrade proteoglycans, unmask VWF binding sites and thus abolish the thromboresistance of the media in human arteries.

Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

Unlabelled: Cocaine abuse is on a rise in Hungary as well. It is known that cocaine users have a higher risk developing cardiovascular complications, for example aortic dissection. Almost all patients in Hungary suffering from type B aortic dissection are referred to our department for treatment., Aim: We introduce the case of a regular cocaine user, who suffered an acute type B aortic dissection and was treated surgically. To our best knowledge this is the first similar case in our country to be published., Method: Case presentation., Results: We performed a successful operation: acute thoracoabdominal aortic refenestration, no complication was detected. The patient is doing well three months after the procedure, returned to his regular activities, he is normotensively receiving medical treatment, and he gave up cocaine., Conclusions: Thoracoabdominal aortic refenestration can save the life of patients presenting with acute type B dissection. Good long-term result depends on adequate hypertension control and cocaine abstinence. As the frequency of cocaine abuse increases in Hungary, similar cases may be more often encountered.

Romhányi's aldehyde-bisulphite-toluidine blue (ABT) topo-optical reaction was checked electron microscopically. The reaction product was found localized on the sarcolemma membrane and intercalated disc. The findings suggest that the topo-optical ABT-reaction is suitable for molecular analysis. In addition to confirming the electron microscopic suitability of the ABT-reaction it has also offered ultrastructural evidence for the reliability of the topo-optical method.

Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an 'ideal' arterial interponate for vascular replacements in the clinical field. An autologous, tubular graft prepared from the posterior rectus fascia sheath was used for iliac artery replacement in dogs for 1, 3, 6 and 12 months. Forty-one grafts were implanted and immunosuppression was used in separate groups. The patency rate was followed by Doppler ultrasound. Thirty-seven grafts remained patent, 2 cases with thrombosis and 2 cases with stenosis occurred. There was no evidence of necrosis or aneurysmatic formation. The histological analysis included conventional light microscopic and immunohistochemical examinations for CD34 and factor VIII. The explanted grafts showed signs of arterialisation, appearance of elastin fibres, and smooth muscle cells after 6 months. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. In conclusion, the autologous graft presents acceptable long-term patency rate. It is easy to handle and the concept of beneficial presence of the anti-clot mesothelium until endothelialisation seems to work. The first clinical use was already reported by our group with more than 2 years survival.

Unlabelled: Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy. Some publications shed light to the role of other viruses in this disease as well. Our molecular investigation has demonstrated that adeno- and herpes viruses might also frequently occur in dilated cardiomyopathy., Aim: The aim of our study was to screen virus genomes in heart tissues from heart-transplanted patients to prove their possible role in the pathogenesis of dilated cardiomyopathy., Methods: DNA and RNA were isolated from five regions of the heart muscle. Amplification for Adenovirus Type 3, Human Herpes Virus Type 6 and Enterovirus genomes were performed by nested-Polymerase Chain Reaction. Finally the virus-positive samples were direct sequenced., Results: In 2 patients Adenovirus Type 3 and in 1 patient both Adenovirus Type 3 and Human Herpes Virus Type 6 were detected. No enteroviruses were found in any heart tissue., Conclusions: In our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues. The identified viral sequences proved previous viral infection, which could have played a role in the development of dilated cardiomyopathy. Detection of different viruses in the myocardium by molecular biological examinations might contribute to adequate treatment of these patients.

Aim: The number of arteriovenous (AV) fistula creation increases worldwide. Haemodialysis is more effective, patients live longer, and they need more access operations. The optimal strategy for the order and sequence of the different type and localization of AV fistulas remains obscure. Based on internationally acclaimed guidelines, autogenous access should be performed whenever possible and the first operation of choice is the radiocephalic fistula at the wrist, the second type is the elbow fistula. The area between the standard exposures means also good access area and its usage is not emphasized properly. Our aim was to study the short and long-term the results of autologous forearm fistulas., Methods: Between 1997 and 2005 we performed 1018 AV shunts in an academic tertiary care centre. Ninety-seven autologous antebrachial AV shunts were performed. The average follow-up time was 31.3 months. We examined the patency rate and its connection with different variables such as diabetes mellitus, acute or chronic operative situations, indications for surgery, diameter and quality of the vein., Results: The primary patency rates were 93%, 79.5% and 61.2% at the end of years 1, 2 and 6, respectively. The patency rate was not significantly affected by any of the examined variables mentioned above., Conclusion: The patency rate of the autologous antebrachial AV shunt is comparable to the wrist and elbow fistulas, so our results support the practice of performing fistula at this atypical localization. Proximal autologous fistulas and prosthetic graft implantation could be postponed, this way valuable time could be saved for the uremic patients.

Background: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization., Objective: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity)., Methods and Results: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi. Oleic acid at relevant concentrations reversibly inhibits more than 90% of the amidolytic activity of plasmin on a synthetic substrate (Spectrozyme PL), but only partially inhibits its fibrinolytic activity measured using turbidimetry. Chromogenic assays detecting the generated plasmin activity show that plasminogen activation by tissue-type plasminogen activator (t-PA) is completely blocked by oleic acid in the fluid phase, but is accelerated on a fibrin matrix. A recombinant derivative of t-PA (reteplase) develops higher fibrin specificity in the presence of oleic acid, because both the inhibition of plasminogen activation in free solution and its enhancement on fibrin template are stronger than with wild-type t-PA., Conclusion: Through the stimulation of plasminogen activation on a fibrin template and the inhibition of plasminogen activators and plasmin in the fluid phase, free fatty acids confine the action of fibrinolytic proteases to the site of clotting, where they partially oppose the thrombolytic barrier function of phospholipids.

Numbers of arteriovenous (AV) fistula creation increase worldwide. Hemodialysis is more effective, patients live longer, they need more access operation. The optimal strategy for the order and sequence of the different type and localization of AV fistulas remains obscure. Based on internationally acclaimed guidelines, autogenous access should be performed whenever possible and the first operation of choice is the radio-cephalic fistula at the wrist, the second type is the elbow fistula. The area between the standard exposures means also good access area and its usage is not emphasized properly. At our department the performance of autogenous fistulas have always been favoured. Beside the wrist radio-cephalic and elbow fistulas a significant number of autologous forearm AV fistulas has been operated. Our aim was to study the short and long term results of the autogenous forearm fistulas at atypical anatomic positions. We also examined whether the patency rate is affected by different variables as diabetes mellitus, acute or chronic operative situation, the indication of surgery, the quality of thrill at the end of shunt creation, the diameter and quality of the vein. Between 1997 and 2005 we performed 1018 AV shunts in an academic tertiary care center. 97 autologous antebrachial AV shunts were performed. The average follow up time was 31.3 months. The primary patency rate was 97%, 92% and 63% at the end of the first, second and sixth years, respectively. The patency rate was not significantly affected by any of the examined variables mentioned above. The patency rate of the autologous antebrachial AV shunt is comparable to the wrist and elbow fistulas, so our results support the practice of performing fistula at this atypical localization. More proximal autologous fistulas and prosthetic graft implantation could be postponed, this way valuable time could be saved for the uremic patients.

Hair analysis for abused drugs has been gaining increasing significance in forensic sciences. Hair is a special matrix for the retrospective investigation of chronic drug abuse or poisoning in criminal cases and allows to demonstrate with sensitive methods even a single administration in low amount. Segmental hair analysis can yield the information about the time course of the substance use. The background of drug incorporation mechanism is not yet understood in full details and cannot be evaluated exactly in all cases. The hair sampling, sample preparation, analytical performance are very important for final results. The outcomes of hair analysis have been reviewed by dividing into six groups: opiates, cocaine, amphetamines, cannabinoids, abused therapeutic drugs and the markers of chronic alcohol consumption.

Introduction: Nowadays more and more couples face the fact that they cannot have babies in spite of many years of trying. The male factor can be identified in about half of these cases., Aim: The aim of this study was to analyse chromosomal alterations in patients with azoospermia. These patients may be candidates for testicular sperm retrieval and intracytoplasmatic sperm injection., Materials and Methods: Preoperative evaluation included routine andrological investigation with 2 semen analysis, ultrasound, hormonal and genetic examination. Traditional histological examination and embryological diagnostic of tissue samples was performed. Cryopreservation of retrieved testicular tissue was also done. Between January 2001 and June 2005 73 biopsies were performed in 71 patients for testicular sperm extraction. In order to obtain an exact diagnosis, the traditional cytogenetic methods and fluorescence in situ hybridization analyses were performed in combination with molecular genetic techniques. Patients were offered to participate in the assisted reproduction programme on the base of their genetic results., Results: In this study, the most characteristic cases were numerical deviations, such as 47,XXY (2 cases), mosaic 47,XXY/49,XXXXY (1 case), 47,XYY (1 case) and mosaic 46,XY/45,X (1 case) karyotypes. Non-obstructive azoospermia was diagnosed in 53 patients (79%)., Conclusions: Authors emphasised the importance of cyto- and molecular examinations in cases of genetical disorders. The results provide a chance for patients to be spared from long-drawn moreover psychological burdening examinations. In addition the costs of different clinical intervention could be saved too.

The impact of presensitized T lymphocytes on the development of chronic allograft nephropathy (CAN) was investigated in nude athymic LEW.RNU recipients of F344 renal allografts. The recipients (n = 8) were reconstituted with 5 x 10(7) T lymphocytes primed against donor skin grafts to induce graft rejection. LEW.RNU (n = 8) and euthymic LEW recipients (n = 6) which underwent no further intervention after transplantation served as control groups. Adoptive transfer of primed T cells induced CAN in LEW.RNU rats. Their kidney function decreased progressively. After 90 days a moderate glomerulopathy, tubular atrophy and interstitial fibrosis were observed, vascular changes were only mild or absent. Cellular infiltrates were predominated by CD4+ T cells and ED1+ macrophages. Deposition of tenascin and laminin was enhanced. Grafts of euthymic recipients displayed only mild signs of CAN according to the Banff criteria. These data implicate an important role for the cellular immune response in the development of CAN.

The objective of this study was to investigate characteristic injuries of pedestrians and bicyclists (unprotected) compared to motor vehicle occupants' (protected) in fatal traffic accidents. Cases of 664 fatal traffic accidents (371 pedestrians, 45 bicyclists, and 248 motor vehicle occupants) were collected from 1999 to 2001 using the database of the Forensic Institute in Budapest. Autopsy reports were analyzed. Location of injuries, blood alcohol levels, seasonal distribution and natural diseases influencing accident outcome were evaluated. For statistical analysis, odds ratio (OR) with 95% confidence interval (CI) was used by a conditional logistic regression. There were substantial differences in distribution of injuries suffered by pedestrians, bicyclists and motor vehicle occupants. Among pedestrians and bicyclists there was a higher rate of head injuries, such as skull fractures, epidural haemorrhage, subdural haemorrhage, brain contusion, and injuries of the lower extremities. Thoracic damages, such as traumatic aortic rupture, hemothorax, and abdominal damages, like liver rupture were dominant in motor vehicle occupants. Considering existing natural diseases, coronary artery disease was the only one with higher occurrence among motor vehicle occupants 24 (9.7%) compared with pedestrians and bicyclist 36 (8.6%). These results underline the importance of preventive strategies in transportation, pointing out that different methods are necessary to reduce fatal injuries of various traffic participants.

Sepsis is the major cause of patient death after orthotopic liver transplantation (OLT). To identify risk factors for sepsis, we analyzed all 199 primary OLTs performed between 1995 and 2004. Patients were divided into 2 groups according to whether they experienced sepsis after liver transplantation. Recipient, perioperative factors, and complications were subjected to univariate analyses. Statistically significant factors were exposed to multivariate analyses: Cox regression and Hosmer-Lemeshow test. Sepsis occurred in 45 (23%) patients. Recipient Child-Pugh score, preoperative broad spectrum antibiotic (meropenem) prophylaxis, intraoperative red blood cell transfusion, starch infusion, postoperative bleeding, hepatic artery thrombosis, and biliary leakage/necrosis were independent risk factors for sepsis. Our results agree with the international experience. A high amount of starch infusion and an extended use of broad spectrum antibiotics for prophylaxis adverse experiences in our center and have been removed from the protocol.

The morphology of canine platelets (changes in size, shape, staining characteristics, degree of activation and clump formation, distribution of granules, appearance of vacuoles on Giemsa-stained smears) was investigated in 20 healthy control and 181 diseased dogs. In the group of the sick dogs 84 animals suffered from disorders affecting directly the haematological parameters or the haematopoietic organs such as bleeding, thymic haemorrhage, haemolytic disorders, lymphoma, immune-mediated thrombocytopenia, and other 97 dogs were affected by other diseases (hepatopathy, nephropathy, hepatic, splenic or intestinal neoplasm, skin diseases, diabetes mellitus, Cushing's syndrome, sepsis). The alterations found in platelet morphology were not specific for any disorder. The most common platelet abnormalities were polychromasia and the presence of giant platelets. These changes occurred in a high number in disorders accompanied by bleeding or haemolysis. Anisocytosis was the most frequent finding in hepatic, splenic or intestinal neoplasms and in certain endocrinopathies. Microcytosis was observed in immune-mediated thrombocytopenia, hepatic neoplasms and endocrine disorders. Extreme platelet activation was common in haemolysis, hepatopathies, neoplastic diseases and sepsis. Vacuolisation was present in thymic haemorrhage, pancreatitis, diabetes mellitus and Cushing's syndrome. A new morphologic phenomenon, i.e. a ring-like formation of granules, was described in the cytoplasm of the platelets both in healthy and diseased animals. In addition, two forms of pathologic granulation were also described for the first time in Giemsa-stained blood smears: the pseudonuclear and the spot-like formation of granules, which were observed especially in disorders affecting the blood cells. The granulation and morphological characteristics of platelets on smears stained by periodic acid-Schiff reaction (PAS) were also studied. Three localisations of granulation were observed, such as peripheral, eccentric and diffuse. The ratio of PAS-positive and -negative platelets was evaluated in several diseases. Our findings support the diagnostic value of platelet evaluation by light microscopy and help clinicians/clinical pathologists to understand why morphologic changes of thrombocytes might be expected in several diseases.

Background: Chlamydia pneumoniae is one of the possible pathogenetic factors of atherosclerotic processes. Foam cell arteriopathy is a generally accepted pathologic feature of chronic liver allograft rejection and has several similarities to the early lesions of atherosclerosis. The aim of the authors' study was to show any existing correlation between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers with chronic rejection., Methods: Ten liver samples from patients with chronic liver rejection including foam cell arteriopathy and 10 liver samples from healthy individuals were analyzed for the presence of Chlamydia pneumoniae by specific immunohistochemistry and polymerase chain reaction (PCR). Liver samples from two transplant patients with chronic liver rejection without any evidence of foam cell arteriopathy and nine patients with acute liver allograft rejection were also investigated by PCR., Results: In all 10 rejected liver samples, Chlamydia pneumoniae was detected by PCR, whereas only one of the healthy control samples and one of the samples with acute rejection were found to be positive. Immunohistochemistry showed similar results. The positive signals of Chlamydia pneumoniae were localized mainly in the hepatocytes, sinusoidal and perisinusoidal cells, and the cells of portal tracts, whereas most of the altered hepatic arteries showed no or very weak positivity., Conclusions: The results strongly suggest an association between the occurrence of Chlamydia pneumoniae and the presence of foam cell arteriopathy in transplanted livers.

Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate], is a UV light stabilizer plastic additive used worldwide. It is a component of many plastic materials used in medical and food industries. Earlier studies demonstrated its in vitro L-type Ca2+ channel and nicotinic acetylcholine receptor blocking properties. Our previous experiments have proved the toxic effects of Tinuvin 770 on isolated rat cardiomyocytes. The present study investigates the cardiotoxic effects of Tinuvin 770 in vivo. Wistar rats were intraperitoneally injected with increasing doses of Tinuvin 770 (1, 10, 100 microg, and 1 mg) 15 times during a 5-week period. Myocardial samples were analyzed by light, electron, and fluorescent microscopy. The lead-acetate method was used to detect intracellular Ca2+, and glyoxylic acid technique to assess alteration in adrenergic innervation. Focal myocytolysis and hypercontraction necrosis could be observed in rats treated with higher doses of Tinuvin 770. In these groups, intracellular Ca2+ accumulation and increased catecholamine release were detected. Tinuvin 770 not only displays L-type Ca2+ channel blocking properties, but can also lead to catecholamine release, similar to effects of the first generation of L-type Ca2+ channel blockers. Morphological results correspond to catecholamine-induced myocardial damage. Current literature, as well as our study, indicates that more detailed toxicological analysis of Tinuvin 770 should be required, and current regulations in medical and food industries should adopt the new results.

A total of 11 human mandibles were subjected to physical impacts under standardised conditions. Two impact sites and directions were tested and the impact load was varied in four steps. Two occlusional strengths were applied and the influence of simulated soft tissue covering was recorded. The deformation of the bones was measured using strain gauge strips located at eight defined sites. In a series of frontal to occipital impacts the frontal areas and the collum showed the largest length changes. Increasing impact intensities led to a proportional increase of the length changes. An increase of the occlusional strength was either protective (at the collum) or it increased the deformation (frontal area). The soft tissue covering was only partly protective. Lateral impact was characterised by a compression on the side of the impact and stretching on the other side only. The intensity and speed of deformation increased with increasing distance from the site of impact. A fixed occlusion caused an increase of compression at the site of impact and an increasing stretching in the frontal part of the bone and at the opposite collum.

Two experiments were performed to evaluate the normal development of the rabbit heart. In the first experiment the most intensive period of heart development was determined in rabbit embryos. The second experiment studied the most intensive period of heart development, determined in the first experiment, by concentrated sampling at 8-hour intervals. After cutting open the uterine wall opposite the discoid placenta, rabbit embryos were removed from the ampullae of the uterus using capillary tubes, under stereomicroscope at fivefold magnification. The embryos were subsequently placed into 4% formalin solution for 24 h. After fixation, slides stained with haematoxylin and eosin were made for histological examination. In the first experiment 51 embryos were examined, while during the second experiment a total of 113 embryos, representing different stages of development, were collected. Finally the data obtained on rabbits were compared with the well-known development of the heart in humans and mice.

A multiple cardiac anomaly in sheep is presented to show how complicated the result of abnormal development can be. The heart of a 12-hour-old sheep was fixed in 8% formaldehyde solution and subsequently dissected by an anatomical method, and the abnormalities were recorded on digital pictures. The abnormal anatomy is described and compared with the simple developmental anomalies. Developmental abnormalities were found in the distal portion of the bulbus, the aortic arches and the interatrial septum. A special type of the double-outlet right ventricle was observed, which was not a real double-outlet ventricle because it occurred in combination with pulmonary atresia. Coarctation of the aorta was seen, the ductus arteriosus was absent, and there were five vessels originating from the aortic arch instead of one vessel seen in normal cases, as a result of the abnormal development of the aortic arches.

Hepatic artery thrombosis is a major cause of graft failure in liver transplantation. Use of donor interponates are common, but results are controversial because of necrosis or thrombosis after rejection. Reperfusion injury, hypoxia and free radical production determinate the survival. The aim of the study was to create an 'ideal' arterial interponate. Autologous, tubular graft lined with mesothelial cells, prepared from the posterior rectus fascia sheath, was used for iliac artery replacement in eight mongrel dogs for six months under immunosuppression. Patency rate was followed by Doppler ultrasound. Eight grafts remained patent and another two are patent after one year. The patency rate was good (median Doppler flow: 370 cm/sec) and there was no necrosis, thrombosis or aneurysmatic formation. The grafts showed viable morphology with neoangiogenesis, appearance of elastin, smooth muscle and endothelial cells. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. Tissue oxygenation was good in all cases with normal (< 30 ng/ml) myeloperoxidase production. In conclusion, this autologous graft presents good long-term patency rate. Viability, arterialisation and low thrombogenicity are prognostic factors indicating usability of the graft in the clinical practice without the risk of rejection. Further investigations such as cell cultures and standardisation are necessary.