The level of complement C3 is associated with the severity of atherosclerosis but not with arterial calcification in peripheral artery disease.

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.

Investigation of changes in psycho-physiological parameters evoked by short duration, intensive physical stress.

The aim of our study was to investigate changes in psycho-physiological parameters evoked by short duration, intensive physical stress on university students practicing judo at different intensities and timely manner. Stability of posture, muscle strength (hand force exertions), attention concentration (choice reaction time), cardiac parameters, (ECG, heart rate, heart rate variability), and oxygen saturation were measured, cardiac state and stress index were computed before and after the physical stress. The actual psychic state of the subjects was evaluated using the Spielberger's STPI-H Y-1 test which determined anxiety, curiosity, anger and depression level. Analysis of psychometric and physiologic parameters indicated significant correlations, among others, between force and cardiac stress (-), force and depression (-), anxiety and errors in actions (+), cardiac state and errors in action (-), cardiac state and depression (-). Paired samples tests showed the influence of intensive physical stress within groups of students, and independent samples tests made it possible to evaluate the power of medical and sport students, performing physical training at a significantly higher level than it is usual among the medical students. Our results proved that higher level physical training influences the psychic state advantageously, limits increases in cardiac stress level, and decreases susceptibility to anxiety and depression.

Skeletal age estimation in Hungarian population of known age and sex.

Several methods of estimating age on the basis of human skeletal remains are used all over the world, methods that were established using known age and sex databases or during medicolegal autopsies. Over the course of the past several decades, many tests have been carried out on various populations to confirm the applicability of these methods in age assessment. While the opinions of experts vary regarding the cranial suture closure techniques, morphology of the sternal end of the fourth rib has been proven to be more accurate as an age assessor. The purpose of this paper is to test the reliability of three age estimation methods on a Central European population. Observation of ecto- and endocranial suture closure after Meindl and Lovejoy and Acsádi and Nemeskéri (239 individuals in the case of Meindl and Lovejoy and 238 in the case of Acsádi and Nemeskéri) and morphology of the sternal ends of the third, fourth and fifth ribs in accordance with Iscan (116 individuals) was done on a Hungarian sample of known sex and age at death at autopsy procedures. According to the observations, (1) the state of ectocranial suture closure was so erratic that it was not useful in age assessment, (2) obliteration phases of the endocranial sutures yield only a rough estimation, and (3) age determination from sternal ends of the ribs was the most reliable, especially with the application of slightly expanded age intervals on the Hungarian population.

Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes.

Foregoing researches made on the N/OFQ system brought up a possible role for this system in cardiovascular regulation. In this study we examined how N/OFQ levels of the blood plasma changed in acute cardiovascular diseases. Three cardiac patient groups were created: enzyme positive acute coronary syndrome (EPACS, n = 10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11). We compared the patients to healthy control subjects (n = 31). We found significantly lower N/OFQ levels in the EPACS [6.86 (6.21-7.38) pg/ml], ENACS [6.97 (6.87-7.01) pg/ml and IHD groups [7.58 (7.23-8.20) pg/ml] compared to the control group [8.86 (7.27-9.83) pg/ml]. A significant correlation was detected between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ depression is in association with the level of ischemic stress and the following inflammatory response. Further investigations are needed to clarify the relevance and elucidate the exact effects of the ischemic stress on the N/OFQ system.

Active metabolites resulting from decarboxylation, reduction and ester hydrolysis of parent drugs.

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.

Patchy myocardial pattern of virus sequence persistence in heart transplant recipients--possible role of sampling error in the etiology.

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.

Hindered dissolution of fibrin formed under mechanical stress.

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.

Neutrophil granulocyte-dependent proteolysis enhances platelet adhesion to the arterial wall under high-shear flow.

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.

The role of autologous antebrachial arteriovenous fistula in the strategy of access planning for chronic uremic patients on hemodialysis.

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.

Fibrinolysis in a lipid environment: modulation through release of free fatty acids.

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.

Common atrioventricular canal in a newborn foal--case report and review of the literature.

This paper presents the embryological and pathological features as well as the terminology and classification of common atrioventricular canal, a type of endocardial cushion defect. The authors give a complete description of an extremely rare congenital cardiac malformation in an equine neonate. The diagnosis of a complete, balanced common atrioventricular canal of type C in Rastelli's classification scheme was based on two-dimensional, contrast and colour Doppler echocardiography and subsequent postmortem gross pathology. To support our diagnosis and study the pathophysiological effect of the alteration, physical examination, blood gas analysis and other laboratory tests, electrocardiography and thoracic radiography were also performed. Our search of the literature suggests that this type of developmental anomaly might account for a higher percentage of equine congenital cardiac defects than was thought earlier. We suppose that some previously described congenital heart abnormalities were misinterpreted: these anomalies could have actually represented some type of atrioventricular canal defect, resulting from the failure of the endocardial cushions to undergo complete and proper fusion.

Morphological evaluation of canine platelets on Giemsa- and PAS-stained blood smears.

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.

Fatal traffic injuries among pedestrians, bicyclists and motor vehicle occupants.

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.

Factors in association with sepsis after liver transplantation: the Hungarian experience.

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.

Experimental vascular graft for liver transplantation.

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.

Deformation characteristics of the human mandible in low impact experiments.

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.

Histological studies on embryonic development of the rabbit heart.

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.

Multiple cardiac anomaly in sheep: a case study and review of the literature.

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.

Portal hypertension in a dog due to circumscribed fibrosis of the wall of the extrahepatic portal vein.

A two-and-a-half-year-old German shepherd dog with ascites and a high concentration of blood ammonia was investigated. Sonographically, its liver was normal but the portal vein was dilated and the flow of blood within it was slow. A liver biopsy showed that the liver was normal, and did not reveal any possible cause of portal hypertension or ascites. Postmortem, the cranial part of the portal vein was dilated with a cross-striped internal surface, but the caudal part looked normal; there was a stenotic ring between the normal and dilated parts. Histology of the dilated segment revealed marked hypertrophy of both the internal circular and the external longitudinal smooth muscle layers. At the site of the stenosis, the longitudinal muscular layer was replaced by connective tissue. Circumscribed fibrosis in the wall of the portal vein was responsible for the stenosis and the subsequent prehepatic portal hypertension. The cross-striped pattern in the dilated part of the vein was the result of hypertrophy of the inner circular smooth muscle layer.

The role of bacterial toxins in sudden infant death syndrome (SIDS).

There is increasing evidence for the involvement of bacterial toxins in some cases of sudden infant death syndrome (SIDS), particularly the pyrogenic toxins of Staphylococcus aureus. This had led to the hypothesis that some SIDS deaths are due to induction of inflammatory mediators by infectious agents or their products during a period in which the infant is unable to control these normally protective responses. The genetic, developmental and environmental risk factors identified for SIDS are assessed in relation to frequency or density of mucosal colonisation by toxigenic bacteria and their effects on induction and control of inflammatory responses to the toxins.