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.

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.

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.

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.

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.

Left ventricular beta 1 and beta 2 adrenoceptor mRNA expression in normal and volume overloaded human heart.

STUDY OBJECTIVE: The aim was to determine gene expressions of beta 1 and beta 2 adrenoceptor subtypes (BAR-1, BAR-2) in normal and volume overloaded human heart. DESIGN: Tissue mRNA levels were determined by excess solution hybridisation using 35S-UTP labelled BAR-1 and BAR-2 cRNA probes. MATERIAL: Atrium, right and left ventricular subendocardium, and papillary muscle from donor hearts and papillary muscle from patients operated for mitral stenosis and mitral regurgitation were studied. MEASUREMENTS AND MAIN RESULTS: The basal levels of myocardial BAR-1 and BAR-2 mRNA expression were similar to the levels in human adipose tissue that have been reported previously from our laboratory (10-15 amol mRNA.micrograms-1 total nucleic acids). No differences in BAR-1 and BAR-2 mRNA expression were observed between various parts of the normal heart. In papillary muscle, BAR-1 and BAR-2 mRNA levels were 8.8 (SEM 5.1) and 10.2(6.6) amol.micrograms-1 total nucleic acids, respectively. Furthermore, no differences in BAR mRNA expression were observed between myocardium subjected to mitral stenosis as compared to normal myocardium. On the other hand, patients with mitral regurgitation expressed significantly lower levels of both BAR-1 and BAR-2 mRNA, at 4.8(1.0) (p less than 0.05) and 2.6(1.1) (p less than 0.001) amol.micrograms-1 total nucleic acids, respectively. The ratio BAR-1/BAR-2 mRNA was higher (p less than 0.01) in mitral regurgitation than in the normal heart. CONCLUSIONS: Myocardium from different parts of the normal human heart, where different pressure work is generated, express similar levels of BAR-1 and BAR-2 mRNA. With volume load a significant decrease in BAR mRNA levels was observed, which was more marked for BAR-2 mRNA. This difference in specific mRNA levels in patients with mitral regurgitation indicates an independent regulation of the expression of these two receptor subtypes.

Lactate dehydrogenase and its isoenzyme activities in different parts of the normal human heart.

Activity and distribution of lactate dehydrogenase (LD) and its isoenzymes (LD1-5) were determined and both the heart (H) and muscle (M) subunit activities were calculated in myocardial samples from six brain dead human organ donors with normal hearts. Ten parts of each heart were analysed. LD1-3 were found to be the main LD isoenzymes. The LD1 activity predominated in all parts analysed. The activities of total LD, H subunit and LD1 increased from atria and auricular appendages via the right ventricle to the left ventricle. The H subunit activity varied more than twofold and the M subunit activity by only 20% between different locations of the heart. The left ventricular papillary muscle was found to have higher activities than other locations of both H and M subunits. It is concluded that the isoenzyme profile could be a metabolic adaptation to divergent work demand on the different heart chambers.

Increase in functional activity rather than in amount of Gi-alpha in failing human heart with dilated cardiomyopathy.

OBJECTIVE: The aim was to investigate whether or not increased pertussis toxin catalysed ADP ribosylation correlates with increased amount of Gi-alpha in failing human heart. DESIGN: Antisera raised against unique synthetic peptides corresponding to alpha subunits of Gs and Gi 1-3 were used in immunoblotting and ELISA to determine amounts of various G proteins. Adenylyl cyclase activity, beta adrenoceptors, and muscarinic receptors were then measured in cardiomyopathic hearts (n = 6) obtained at transplant in order to study whether or not an altered expression of G proteins has relevance to the integrity and function of the receptor--adenylyl cyclase system. Six non-failing control hearts were also studied. RESULTS: No significant differences in the peptide equivalent amounts of either Gs or Gi were found in the failing human heart as compared to the non-failing heart. However, functional activity of Gi was shown to increase significantly since there was a decrease in basal (57%), isoprenaline stimulated (60%), and guanyliminodiphosphate stimulated (52%) adenylyl cyclase activity. In contrast the density of beta adrenoceptors was markedly decreased (51%) in failing human heart in comparison to non-failing hearts. Neither the density nor the affinity of muscarinic receptors changed in the failing human heart. CONCLUSION: These results suggest that in the failing human heart, there is an increase in functional activity rather than in amount of Gi, and an important part of functional expression of Gi-alpha may be regulated at the post-translational level.

Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy.

OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.

Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective.

The recently discovered hormone, ghrelin, has been recognized as an important regulator of GH secretion and energy homeostasis. Orexigenic and adipogenic ghrelin is produced by the stomach, intestine, placenta, pituitary, and possibly in the hypothalamus. The concentration of circulating ghrelin, principally derived from the stomach, is influenced by acute and chronic changes in nutritional state. To date, most studies focused on the role of ghrelin in GH secretion or its function in complementing leptin action to prevent energy deficits. The potential significance of ghrelin in the etiology of obesity and cachexia as well as in the regulation of growth processes is the subject of ongoing discussions. A large quantity of information based on clinical trials and experimental studies with ghrelin and previously available synthetic ghrelin receptor agonists (GH secretagogues) must now be integrated with a rapidly increasing amount of data on the central regulation of metabolism and appetite. In this overview, we summarize recent findings and strategies on the integration of ghrelin into neuroendocrine networks that regulate energy homeostasis.

Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims.

BACKGROUND: There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in brain regions of depressed suicide victims and in platelets of depressed suicidal subjects. The present investigation tested the hypothesis that these changes in the serotonergic system in depressed suicide victims are trait rather than state markers and associated with a polymorphism in respective candidate genes. METHODS: Two polymorphic variants (102T/C polymorphism and His452Tyr functional polymorphism) of the 5-HT2A receptor gene and a functional polymorphism in the 5' regulatory region of the 5-HT transporter gene, have been determined in genomic DNA obtained from postmortem brain samples of 24 depressed suicide victims and 31 control subjects of the same ethnic background. In a subset of subjects, density (Bmax) of 5-HT uptake sites (labeled with 3H-paroxetine) and of 5-HT2A receptors (labeled with 3H-ketanserin) was also determined in prefrontal cortex samples. RESULTS: The major finding of this study was a significantly higher frequency of the 5-HT transporter gene long (L) allele (chi 2 = 3.9, df = 1; p = .048) in depressed suicides. No significant differences between suicides and controls were observed for the 102T/C polymorphism and His452Tyr polymorphism of 5-HT2A receptor gene. The density of 3H-paroxetine binding sites tended to be higher in subjects expressing the short (S) allele of 5-HT transporter gene. Furthermore, there was a significant difference in serotonin transporter binding sites between the genotype S/S and combined genotypes S/L and L/L. CONCLUSIONS: Our finding provides the first evidence suggesting that a functional polymorphism in the regulatory region of serotonin transporter gene may be associated with suicide in depressed subjects.

Preprotachykinin-A mRNA expression in the human and monkey brain: An in situ hybridization study.

The mRNA expression for preprotachykinin-A (PPT-A) was studied throughout the human and cynomolgus monkey brain to assess the neuroanatomical expression pattern of the PPT-A gene in primates. In situ hybridization showed that the PPT-A mRNA is expressed highly in specific regions of the postmortem human brain, including the striatum, islands of Calleja, hypothalamus (posterior, premammillary, medial mammillary, and ventromedial nuclei), superior and inferior colliculi, periaqueductal gray, and oculomotor nuclear complex. PPT-A mRNA-expressing neurons also were present in the paranigralis (ventral tegmental area) and were scattered in the bed nucleus stria terminalis throughout the sublenticular substantia innominata region, including the diagonal band of Broca and the nucleus basalis of Meynert. In the hippocampus, high PPT-A mRNA expression was localized predominantly to the polymorphic layer of the dentate gyrus; no labeled cells were present in the granular layer. Positively labeled cells also were found scattered in the CA regions as well as in the amygdaloid complex. Neocortical expression of PPT-A mRNA was localized mainly to the deep laminae (layers V/VI), except for the striate cortex (labeling was seen also in superficial layers). The subiculum, thalamus, globus pallidus, ventral pallidum, substantia nigra pars compacta, red nucleus, pontine nuclei, and cerebellum were characterized by very weak to undetectable expression of PPT-A mRNA. An expression pattern was evident in the monkey forebrain similar to that observed in the human, except for the absence of PPT mRNA-expressing cells in the medial mammillary nucleus despite intense expression in supramammillary, lateral mammillary, and premammillary nuclei. Overall, more similarities than differences are apparent between primate species in the expression pattern of the PPT-A gene. J. Comp. Neurol. 411;56-72, 1999.

Modular distribution of vasoactive intestinal polypeptide in the rat barrel cortex: changes induced by neonatal removal of vibrissae.

The distribution of vasoactive intestinal polypeptide-immunoreactive neuronal structures in the barrel cortex (posteromedial barrel subfield) of adult rats was analysed after unilateral removal of the vibrissal follicles of row C in neonatal rats. The hypothesis was tested whether the distribution of vasoactive intestinal polypeptide-immunoreactive structures depends on the normal anatomical organization of the specific sensory input. After three months survival the distribution of the vasoactive intestinal polypeptide-immunoreactive structures was morphometrically evaluated. This approach revealed alterations in the contralateral posteromedial barrel subfield, where the disappearance of barrel row C and a substantial increase in size mainly of barrel row D, but also of other rows could be detected. Increase in row D included both barrels and the interspace (septal segments between barrels in one row). As vasoactive intestinal polypeptide immunoreactivity of the barrel field was found previously to be localized in synaptic boutons involved in symmetric synapses, our present findings suggest that (i) the interspace is enriched in inhibitory vasoactive intestinal polypeptide-immunoreactive synapses as opposed to the excitatory thalamocortical input reaching the barrel hollow, (ii) the spatial distribution of the vasoactive intestinal polypeptide system in the barrel cortex is closely associated with the neuronal organization of the sensory input and reacts with a considerable plasticity to lesion-induced changes of the input, and (iii) the compensatory barrel hypertrophy in a row neighbouring the deafferented row involves an increasing number of vasoactive intestinal polypeptide-immunoreactive synapses per barrel.

Rupture of the myocardial histoskeleton and its relation to sudden death after infusion of glycine 1.5% in the mouse.

Hypoxic lesions in the subendocardium and long-standing dilatation of the interstitium have been described after exposure of the heart to glycine 1.5%, which is a widely used irrigating medium in endoscopic surgery. To study if the hypo-osmotic properties of the fluid cause these morphological changes, whether their long duration can be explained by rupture of the histoskeleton and whether they promote sudden death, 75 mice received an intravenous infusion of 200 ml/kg or 300 ml/kg over 60 min of either glycine 1.5%, glycine 1.5% in normal saline, normal saline, or no fluid (controls). The animals were decapitated when they were dying from the infusion, or else 7 days later, and 69 hearts were examined by light microscopy and 4 by electron microscopy. Rupture of the histoskeleton and hypoxic lesions in the subendocardium were observed in 47% and 35%, repectively, of the mice given glycine 1.5%, while the incidence averaged 20% in the two other groups. Rupture occurred in 38% of the mice that died, in 23% of those that survived an infusion, and in 0% of the controls. Hypoxic changes correlated with bradycardia, which is a sign of glycine absorption in the clinic. In conclusion, rupture of the histoskeleton and hypoxic changes occur in the subendocardium of mice after volume loading. These morphological changes were aggravated by the hypo-osmotic properties of glycine 1.5%.

Application of a vascular graft material (Solcograft-P) in experimental surgery.

The implantation and post-implantation behaviour of a Solcograft-P vascular prosthesis in the aortic, aorto-iliac, carotid and vena caval positions in dogs was studied up to 100 d post-surgery in order to assess the suitability of this vascular material for use in man. Solcograft-P is prepared from the carotid arteries of calves by crosslinking the collagen stroma using adipyl dichloride. During the postoperative follow-up period of 3 month, 100% of the aortal grafts, 80% of the aorto-iliac bypasses, 60% of the vena caval grafts and 35% of the carotid implants remained patent. The biochemical properties of the Solcograft-P are better than those of Solcograft, its predecessor. The intimal lining was consistently smooth and homogeneous in grafts of biological origin, and no aneurysm was observed. Infection and early thrombosis occured no more frequently than with other grafts. The new Solcograft-P, crosslinked via ester and amide groups, seems to represent a real improvement over Solcograft. Our results suggest that Solcograft-P should prove valuable in various cases of reconstructive vascular surgery of the lower limb, especially when the autologous vena saphena magna is not available, and its mechanical properties may well prove suitable for both arterial and venous replacement.

Myoglobin content and citrate synthase activity in different parts of the normal human heart.

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.

Slices from the rat olfactory bulb maintained in vitro. Morphological aspects.

Transverse, 400-microns-thick slices of 8-day-old rat olfactory bulb were incubated in Krebs-Henseleit medium with and without oxygenation. Following incubation, slices were fixed in aldehyde-osmium and embedded in resin for light and electron microscopy. After 2 h of incubation oxygenated preparations showed a structural preservation comparable to that of the freshly fixed olfactory bulb. Under hypoxic conditions mitral cells located on the medial side of the bulb were the most sensitive to the interruption of gassing, while ventricular cells and glomeruli were remarkably resistant as judged by morphological standards. The effects of short-term (up to 30 min) interruptions of gassing proved to be reversible. Our findings suggest that the incubated olfactory bulb slice may be a useful preparation for functional morphological studies.

Vasoactive intestinal polypeptide immunoreactive structures in the mouse barrel field.

Immunohistochemistry for vasoactive intestinal polypeptide was carried out in tangentially cut vibratome sections of the barrel cortex in adult mice. Sections through layer IV have revealed an association between the cytoarchitectonically visible modular organization of barrels and the distribution of immunoreactive axon terminals. These terminals are preferentially localized in the side region of a barrel, whereas the hollow shows a relative scarcity of these structures as shown with image analysis. This finding is the first direct demonstration of a modular distribution of vasoactive intestinal polypeptide-containing axon terminals in the neocortex.

5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala.

The density (Bmax) of 5-HT2 receptors labelled with [3H]ketanserin was significantly increased in prefrontal cortex (by 67%) and amygdala (by 97%) from suicide/depressives in comparison with controls. There were no differences in Kd of [3H]ketanserin binding between the two groups. The density (Bmax) and affinity (Kd) of [3H]paroxetine sites were not significantly different in the suicide/depressives and controls. The ratio between the density of presynaptic 5-HT uptake sites and postsynaptic 5-HT2 receptors in amygdala was significantly lower in suicide/depressives than in controls. The data confirm and extend some of the previous findings of increases in 5-HT2 receptors in post-mortem brains of suicide victims and depressives who died of natural causes and lend support to the view that an abnormality in brain serotonergic system is associated with depression and suicidal behaviour.