RÉSUMÉ
A 31-year-old female asthmatic patient received an infusion of metamizole and tramadol for chronic pain at a GP surgery. After a few minutes, the patient developed breaing difficulties and died in spite of resuscitation measures. The general practitioner was suspected of medical malpractice. Medico-legal investigations confirmed the assumption that death was caused by anaphylacitic shock. In spite of temporary intubation into the oesophagus no evidence of medical malpractice was found, however.
Sujet(s)
Anaphylaxie/anatomopathologie , Métamizole sodique/effets indésirables , Hypersensibilité médicamenteuse/anatomopathologie , Oesophage/traumatismes , Oesophage/anatomopathologie , Médecine générale/législation et jurisprudence , Intubation trachéale/effets indésirables , Orientation vers un spécialiste/législation et jurisprudence , État de mal asthmatique/traitement médicamenteux , Tramadol/effets indésirables , Adulte , Bronches/anatomopathologie , Cause de décès , Métamizole sodique/pharmacocinétique , Métamizole sodique/usage thérapeutique , Issue fatale , Femelle , Humains , Perfusions veineuses , Poumon/anatomopathologie , Mastocytes/anatomopathologie , Oedème pulmonaire/anatomopathologie , Tramadol/pharmacocinétique , Tramadol/usage thérapeutiqueRÉSUMÉ
A 23-year-old woman was mortally afraid of dental interventions and decided to have her four wisdom teeth removed by outpatient surgery under endotracheal anaesthesia. According to the files, the patient was categorized as ASA I and Mallampati II, and surgery was considered an elective routine intervention. Soon after initiation of anaesthesia, O2 saturation and blood pressure dropped, and the young woman died shortly afterwards in spite of immediate resuscitation measures. At first, an allergic reaction to succinylcholine, which had been administered as a muscle relaxant, was suspected. Autopsy and histological examination showed haemorrhagic pulmonary oedema and a defined lesion in the midportion of the oesophageal mucosa in spite of correct placement of the endotracheal breathing tube. Ultimately, misintubation into the oesophagus, which had not been noticed at first, was determined as cause of death.
Sujet(s)
Anesthésie générale/effets indésirables , Oesophage/traumatismes , Intubation trachéale/effets indésirables , Muqueuse/traumatismes , Extraction dentaire , Oesophage/anatomopathologie , Femelle , Hémorragie/étiologie , Hémorragie/anatomopathologie , Humains , Muqueuse/anatomopathologie , Oedème pulmonaire/étiologie , Oedème pulmonaire/anatomopathologie , Jeune adulteRÉSUMÉ
PURPOSE: The presented case deals with an unusual suicide by carbon monoxide poisoning. In a car parked in a highway rest area, the body of a middle-aged man was found. In the open trunk of the car there was a gas-powered generator which was switched on, but no longer running. The tank was three quarters full. At autopsy, bright-red livores, cherry-pink fingernails, cherry-red blood and salmon-red skeletal musculature were found. According to the toxicological analysis performed during autopsy, the COHb content in the corpse blood was 68%. METHODS: To reconstruct the event, the emergency generator was started again in the man's car. By means of measuring probes placed in the interior of the car, carbon monoxide, carbon dioxide and oxygen were measured and recorded in a concentration-time curve; the concentration of cyanide was measured at the end of the experiment. RESULTS: The lower explosion limit of 500 ppm CO was reached after 30s already. For technical reasons, no further values could be recorded. After about 14 min the engine started stuttering with approximately 14 vol.% of oxygen in the air, but continued to run at a lower speed until the experiment was stopped after 25 min. The final concentration of cyanide was 7.5 ppm. CONCLUSION: In view of the rapid CO increase in the interior of the vehicle it is to be assumed that the victim lost consciousness very fast.
Sujet(s)
Intoxication au monoxyde de carbone/étiologie , Ressources de production d'énergie , Suicide , Automobiles , Intoxication au monoxyde de carbone/anatomopathologie , Carboxyhémoglobine/analyse , Essence , Humains , Mâle , Adulte d'âge moyenRÉSUMÉ
The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways. We performed single-cell analyses of neurons with different vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2 pyramidal cells from the hippocampus, granule cells from the cerebellum (low vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi trigemini, characterized by early neurophysiological deficits) at progressive Braak stages compared to age-matched controls. The highly vulnerable CA1 pyramidal neurons were characterized by age- and disease-unrelated increases in PRCKB levels and by age- and disease-related increases in MAPK1 levels. In contrast, low PRKCB levels were found in CA2 pyramidal neurons, and MAPK1 levels were elevated in controls and intermediate AD stages. Both PRKCB and MAPK1 were increased in the late AD stages. MAPK1 and PRKCB levels were low in the brainstem and cerebellum. We propose that alterations in the expression of these two genes occur early in the pathogenesis of AD in a region-specific manner. In addition, multiple signal transduction pathways need to be affected to result in AD instead of physiological aging.
Sujet(s)
Maladie d'Alzheimer/anatomopathologie , Encéphale/métabolisme , Encéphale/anatomopathologie , Neurones/métabolisme , Transduction du signal/physiologie , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Régulation de l'expression des gènes , Humains , Microdissection au laser , Mâle , Adulte d'âge moyen , Mitogen-Activated Protein Kinase 1/génétique , Mitogen-Activated Protein Kinase 1/métabolisme , Protein kinase C beta/génétique , Protein kinase C beta/métabolisme , ARN messager/métabolismeRÉSUMÉ
The present case deals with the unusual suicide method of a 36-year-old man who fastened one end of a nylon rope to a tree, guided the other end into a van through the open tailgate and placed the loop round his neck. Then he stepped on the accelerator. Before, he had marked the point on the ground where the rope would tighten. As the rope tightened complete decapitation occurred at a speed of about 35 km/h. Autopsy showed a nearly circular abrasion zone around the site of transection slightly ascending towards the nape, a fracture of the cervical spine between the 3rd and 4th vertebra and a fracture of the thoracic spine between the 7th and 8th vertebra. The test for air embolism of the heart was positive. Macroscopically, no evidence of blood aspiration was found. Histological investigation showed general anaemia and minor blood aspiration in the lungs. Wound morphology was largely in line with the injury patterns described after decapitation in the literature. However, our results differed in that blood aspiration was discernible only under the microscope and there was a second fracture of the spine. Decapitation as a suicide method is an expression of enormous autoaggression and is categorized as a "hard" suicide method. It is used predominantly by men and its occurrence in the spectrum of suicidal actions is rare. Police investigations revealed that the man had led a sort of double life with a sexually motivated background and had suffered from depressive episodes.
Sujet(s)
Accidents de la route , Décollation/diagnostic , Médecine légale/instrumentation , Polytraumatisme/diagnostic , Fractures du rachis/diagnostic , Suicide , Adulte , Diagnostic différentiel , Issue fatale , Humains , MâleRÉSUMÉ
Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer´s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage and increase with age. To unravel the impact of mtDNA damage on AD development, we analyzed mtDNA deletion levels in diverse neuronal cell types of four brain regions (hippocampal CA1 and CA2 regions, nucleus tractus spinalis nervi trigemini, and the cerebellum) that exhibit differing levels of vulnerability to AD related changes at progressive Braak stages compared with age-matched controls. Neurons from these four brain regions were collected using laser microdissection, and analyzed using quantitative polymerase chain reaction (qPCR). Although, no correlation between mtDNA deletion levels and AD progression were found, the data revealed regional and cell type specific selective vulnerability towards mtDNA deletion levels. In conclusion, unexpected results were obtained as granule cells from the cerebellum and neurons from the nucleus tractus spinalis nervi trigemini of the brain stem displayed significant higher mtDNA deletion levels than pyramidal cells from hippocampal CA1 and CA2 region in age and AD.
Sujet(s)
Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , ADN mitochondrial/génétique , Délétion de gène , Neurones/anatomopathologie , Humains , Neurones/métabolismeRÉSUMÉ
OBJECTIVES: Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue. METHODS: We determined the Michaelis-Menten constant (K(M)) and the maximal velocity (V(Max)) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays. RESULTS: We found the Michaelis-Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters. CONCLUSIONS: These results add further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD.
Sujet(s)
Maladie d'Alzheimer/diagnostic , Maladie d'Alzheimer/enzymologie , Hippocampe/enzymologie , Hippocampe/anatomopathologie , Xanthine oxidase/métabolisme , Sujet âgé , Diagnostic , Femelle , Humains , Mâle , Stress oxydatif , Projets pilotesRÉSUMÉ
A growing body of literature suggests persistent and selective structural changes in the cortico-limbic-thalamic-striatal system in patients with recurrent depressive disorder (DD). Oxidative stress is thought to play a key role in these processes. So far, the main scientific focus has been on antioxidant enzymes in this context. For the first time, this proof of concept study examines the activity of the free radicals producing the enzyme, xanthine oxidase (XO), directly in the cortico-limbic-thalamic-striatal system of patients with recurrent depression. The activity of XO was ascertained in the cortico-limbic-thalamic-striatal regions in post-mortem brain tissue of patients with recurrent depressive episodes and individuals without any neurological or psychiatric history (7/7). We measured the XO activity in following brain areas: hippocampus, regio entorhinalis, thalamus, putamen and caudate nucleus. In this study, we report a significant increase of XO activity in the thalamus and the putamen of patients with depression. Our findings contribute to the growing body of evidence suggesting that oxidative stress plays a pivotal role in certain brain areas in recurrent depressive disorder.
Sujet(s)
Trouble dépressif/enzymologie , Putamen/enzymologie , Thalamus/enzymologie , Xanthine oxidase/analyse , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Analyse de variance , Encéphale/enzymologie , Trouble dépressif/physiopathologie , Femelle , Hippocampe/enzymologie , Humains , Mâle , Adulte d'âge moyen , Stress oxydatif/physiologie , Putamen/physiopathologie , Analyse de régression , Facteurs sexuels , Statistique non paramétrique , Thalamus/physiopathologie , Xanthine oxidase/métabolismeRÉSUMÉ
For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD.
Sujet(s)
Aldehyde dehydrogenase/métabolisme , Maladie d'Alzheimer/métabolisme , Maladie d'Alzheimer/anatomopathologie , Mitochondries/enzymologie , Putamen/métabolisme , Putamen/anatomopathologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Vieillissement , Acides gras insaturés/métabolisme , Femelle , Humains , Peroxydation lipidique , Mâle , Stress oxydatif/physiologie , Cortex préfrontal/métabolisme , Cortex préfrontal/anatomopathologie , Espèces réactives de l'oxygèneRÉSUMÉ
In the pigmented dopaminergic neurons of the human substantia nigra pars compacta the system relevant in iron storage is the polymer neuromelanin (NM). Although in most cells this function is mainly accomplished by ferritin, this protein complex appears not to be expressed in NM-containing neurons. Nevertheless the conceivable presence of iron-storing proteins as part of the NM granules has recently been discussed on the basis of Mössbauer spectroscopy and synchrotron x-ray microspectroscopy. Intriguingly by combining subcellular fractionation of NM granules, peptide sequencing via tandem mass spectrometry, and the additional confirmation by multiple reaction monitoring and immunogold labeling for electron microscopy, L-ferritin could now be unambiguously identified and localized in NM granules for the first time. This finding not only supports direct evidence for a regulatory role of L-ferritin in neuroectodermal cell pigmentation but also integrates a new player within a complicated network governing iron homeostasis in the dopamine neurons of the human substantia nigra. Thus our finding entails far reaching implications especially when considering etiopathogenetic aspects of Parkinson disease.
Sujet(s)
Apoferritines/analyse , Granulations cytoplasmiques/composition chimique , Mélanines/analyse , Substantia nigra/composition chimique , Technique de Western , Chromatographie en phase liquide à haute performance , Granulations cytoplasmiques/ultrastructure , Électrophorèse sur gel de polyacrylamide , Humains , Microscopie immunoélectronique , Modifications postmortem , Protéomique/méthodes , Spectrométrie de masse ESI , Substantia nigra/ultrastructureRÉSUMÉ
INTRODUCTION: A growing body of evidence suggests that the glial cell line-derived neurotrophic factor (GDNF) is involved in the aetiopathology of mood disorders. GDNF is a neurotrophic factor from the transforming growth factor-beta-family, playing a role in cell development and function in the limbic system. This is the first study to examine GDNF concentration in different brain regions of patients with depressive disorder (DD). MATERIAL AND METHODS: We used sandwich-ELISA-technique to ascertain GDNF concentration and Lowry assay for overall protein levels in post-mortem brain tissue of 7 patients with recurrent depressive disorder and 14 individuals without any neurological or psychiatric diagnoses. We included cortical regions as well as limbic area's (hippocampus, entorhinal cortex) basal ganglia (putamen, caudate nucleus), thalamus and cingulated gyrus. RESULTS: We found a significant increase in GDNF concentration in the parietal cortex of patients with DD compared to the control group. In other regions the trend of an increased GDNF concentration did not reach statistical difference. DISCUSSION: This proof of concept study supports previous findings of an alteration of the GDNF in patients with depressive disorder. However, for the first time a significant increase of GDNF in a cortical brain area was found in DD.
Sujet(s)
Encéphale/anatomopathologie , Trouble dépressif/anatomopathologie , Facteur neurotrophique dérivé des cellules gliales/analyse , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Cartographie cérébrale , Test ELISA , Femelle , Hippocampe/anatomopathologie , Humains , Mâle , Adulte d'âge moyen , Lobe pariétal/anatomopathologie , Valeurs de référenceRÉSUMÉ
Recent research has demonstrated that early life experience, such as variation in maternal care, can have a profound impact on the physiological and endocrine stress response of Rattus norvegicus. Low maternal care resulted in increased methylation of the nerve growth factor-inducible protein A (NGFI-A, EGR1) binding site located in the hippocampal glucocorticoid receptor gene (Nr3c1) exon 1(7) promoter, leading to decreased Nr3c1 expression, which results in a reduced efficiency of glucocorticoid-mediated negative feedback on hypothalamus-pituitary-adrenal axis activity. The human glucocorticoid receptor gene (NR3C1) has a highly similar 5' structure compared to the rat, and the human alternative exon 1-F is the orthologue to the rat exon 1(7). Based upon the evidence from rats, and the high sequence identity of the regulatory sequences, we examined the methylation pattern of the corresponding NGFI-A binding site in the human glucocorticoid receptor exon 1-F specific promoter in post mortem hippocampal tissue. In contrast to the findings in rats, neither of the two CpG motifs within the NGFI-A binding site was methylated in the 32 subjects investigated. These observations might reflect different promoter methylation patterns in humans and rats.
Sujet(s)
Méthylation de l'ADN , Exons , Hippocampe/physiologie , Régions promotrices (génétique) , Récepteurs aux glucocorticoïdes/génétique , Protéines de répression/métabolisme , Autopsie , Séquence nucléotidique , Sites de fixation , ADN/génétique , ADN/isolement et purification , Régulation de l'expression des gènes , Humains , Données de séquences moléculaires , Récepteurs aux glucocorticoïdes/métabolismeRÉSUMÉ
Regular necrophilia refers to the sexually motivated abuse of corpses and is not considered as severe crime in many western countries. However, the risk of "switching" to necrophilic homicides, i.e., committing a homicide to obtain a dead body, has to be assessed by forensic experts. We present a case of semi-professional dissection, preservation and sexual abuse of the body and body parts of a 14-year-old girl. Every step was documented by the offender on thousands of digital images thus allowing an exact reconstruction of necrophilic acts and fantasies. Three months after the disappearance of the body the remains could be recovered and linked to the deceased by pathological examination and DNA analysis. The offender had excessively used the internet for downloading files with sadistic and necrophilic contents including autopsy instructions. The psychiatric examination of the socially integrated and married patient revealed a severe personality disorder. Two other, previously unsolved cases could be attributed to him showing a clear progression of fantasies and acts.
Sujet(s)
Dissection , Paraphilies/psychologie , Photographie (méthode) , Infractions sexuelles/psychologie , Adolescent , Femelle , Psychiatrie légale , Humains , Traitement d'image par ordinateur , Internet , Troubles de la personnalité/diagnosticRÉSUMÉ
In the last decade an important role for the progression of neuronal cell death in Alzheimer's disease (AD) has been ascribed to oxidative stress. trans-4-Hydroxy-2-nonenal, a product of lipid peroxidation, forms conjugates with a variety of nucleophilic groups such as thiols or amino moieties. Here we report for the first time the quantitation of glutathione conjugates of trans-4-hydroxy-2-nonenal (HNEGSH) in the human postmortem brain using the specific and very sensitive method of electrospray ionization triple quadrupole mass spectrometry (ESI-MS-MS). Levels of HNEGSH conjugates calculated as the sum of three chromatographically separated diastereomers were determined in hippocampus, entorhinal cortex, substantia innominata, frontal and temporal cortex, as well as cerebellum from patients with AD and controls matched for age, gender, postmortem delay and storage time. Neither age, nor postmortem delay, nor storage time did correlate with levels of HNEGSH conjugates which ranged between 1 and 500 pmol/g fresh weight in the brain areas examined. The brain specimen from patients with clinically and neuropathologically probable AD diagnosed according to criteria of the consortium to establish a registry for AD (CERAD) show increased levels of HNEGSH in the temporal and frontal cortex, as well as in the substantia innominata. Classification of disease severity according to Braak and Braak, which takes into consideration the amount of neurofibrillary tangles and neuritic plaques, revealed highest levels of HNEGSH in the substantia innominata and the hippocampus, two brain regions known to be preferentially affected in AD. These results substantiate the link between conjugates of glutathione with a product of lipid peroxidation and Alzheimer's disease and justify further studies to evaluate the role of HNE metabolites as potential biomarkers for disease progression in AD.
Sujet(s)
Aldéhydes/métabolisme , Maladie d'Alzheimer/métabolisme , Encéphale/métabolisme , Glutathion/métabolisme , Peroxydation lipidique/physiologie , Stress oxydatif/physiologie , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Maladie d'Alzheimer/physiopathologie , Encéphale/anatomopathologie , Encéphale/physiopathologie , Femelle , Hippocampe/métabolisme , Hippocampe/anatomopathologie , Hippocampe/physiopathologie , Humains , Mâle , Spectrométrie de masse/méthodes , Dégénérescence nerveuse/métabolisme , Dégénérescence nerveuse/physiopathologie , Enchevêtrements neurofibrillaires/métabolisme , Enchevêtrements neurofibrillaires/anatomopathologie , Neurones/métabolisme , Neurones/anatomopathologie , Plaque amyloïde/métabolisme , Plaque amyloïde/anatomopathologie , Substance innominée/métabolisme , Substance innominée/anatomopathologie , Substance innominée/physiopathologie , Substantia nigra/métabolisme , Substantia nigra/anatomopathologie , Substantia nigra/physiopathologie , Régulation positive/physiologieRÉSUMÉ
Movement disorders are a common neurological complication of immunodeficiency virus infection and are thought to result from dopaminergic dysfunction in the basal ganglia. We measured levels of dopamine, and its metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid, in the putamen of healthy and simian immunodeficiency virus (SIV)-infected rhesus monkeys from infection until the development of AIDS. Changes in expression levels of cAMP response element binding protein (CREB), a transcription factor involved in the signalling pathway of dopamine, were also examined. Furthermore, we isolated microglia from the same animals and investigated their activation status in order to explore whether neurochemical findings are associated with immune activation. Plasma and CSF viral RNA load, T-cell analysis and basal ganglia histopathology provided information about disease progression in the animals. Putamen dopamine content was significantly reduced within 3 months of SIV infection, due to decreased dopamine synthesis initially, followed by loss of tyrosine hydroxylase-positive cells in substantia nigra, and accompanied by a decrease in total CREB expression. Pharmacological manipulation of dopaminergic tone with L-DOPA and selegiline showed that the reduction in CREB expression was due to reduced levels of dopamine. These neurochemical changes were significantly correlated with microglia activation in the absence of gross histopathological lesions. Our data demonstrate that putamen dopaminergic function is impaired during SIV infection and indicate that microglia may trigger endogenous mechanisms involved in the dysfunction of dopaminergic systems.
Sujet(s)
Encéphale/physiopathologie , Dopamine/physiologie , Microglie/physiologie , Syndrome d'immunodéficience acquise du singe/physiopathologie , Transmission synaptique/physiologie , Animaux , Technique de Western , Encéphale/virologie , Séparation cellulaire , Chromatographie en phase liquide à haute performance , Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Évolution de la maladie , Dopamine/métabolisme , Électrophorèse sur gel de polyacrylamide , Femelle , Cytométrie en flux , Acide homovanillique/métabolisme , Immunohistochimie , Lymphocytes/physiologie , Macaca mulatta , Mâle , Putamen/métabolisme , Putamen/physiologie , Transduction du signal/physiologie , Syndrome d'immunodéficience acquise du singe/virologie , Tyrosine 3-monooxygenase/métabolisme , Charge viraleRÉSUMÉ
"Subcellular proteomics" is currently the most effective approach to characterize subcellular compartments. Based on the powerful combination of subcellular fractionation and protein identification by LC-MS/MS we were able for the first time to 1) isolate intact neuromelanin granules from the human brain and 2) establish the first protein profile of these granules. This compartment containing neuromelanin (NM) is primarily located in the primate's substantia nigra, one of the main brain regions that severely degenerates in Parkinson disease. We used mechanic tissue disaggregation, discontinuous sucrose gradient centrifugation, cell disruption, and organelle separation to isolate NM granules from human substantia nigra. Using transmission electron microscopy we demonstrated that the morphological characteristics of the isolated NM granules are similar to those described in human brain tissue. Fundamentally we found numerous proteins definitely demonstrating a close relationship of NM-containing granules with lysosomes or lysosome-related organelles originating from the endosome-lysosome lineage. Intriguingly we further revealed the presence of endoplasmic reticulum-derived chaperones, especially the transmembrane protein calnexin, which recently has been located in lysosome-related melanosomes and has been suggested to be a melanogenic chaperone.
Sujet(s)
Granulations cytoplasmiques/métabolisme , Mélanines/métabolisme , Substantia nigra/métabolisme , Calnexine/métabolisme , Centrifugation en gradient de densité , Chromatographie en phase liquide à haute performance , Granulations cytoplasmiques/ultrastructure , Électrophorèse sur gel de polyacrylamide , Humains , Lysosomes/métabolisme , Microscopie électronique à transmission , Peptides/analyse , Protéomique , Spectrométrie de masse ESI , Fractions subcellulaires/métabolisme , Substantia nigra/ultrastructureRÉSUMÉ
In a knife attack the perpetrator can unintentionally injure his own hand, if the knife does not have an adequate handguard and the tip of the blade hits a solid, mostly bony structure while being violently thrust into the victim's body. The injuries occurring under these conditions are localized on the flexor side of the knife-holding hand and may include the index, middle, ring and little fingers. They are seen particularly often on the little finger at the level of the proximal phalanx and in the skin fold of the proximal interphalangeal joint. The majority of these cuts run transversely to the longitudinal axis of the fingers and can show a step-like arrangement with different distances to the metacarpophalangeal joints, often from ulnar-proximal to radial-distal. In the six cases presented the injuries were most pronounced on the ulnar side of the hand. When the flexor tendons of the fingers are also severed and the tendon stumps are strongly retracted this indicates that the fist was firmly closed at the time of the injury.
Sujet(s)
Anatomopathologie légale/méthodes , Blessures de la main/anatomopathologie , Plaies pénétrantes/anatomopathologie , Adolescent , Adulte , Sujet âgé , Phénomènes biomécaniques , Femelle , Traumatismes du doigt/anatomopathologie , Humains , Mâle , Adulte d'âge moyen , Traumatismes des tendons/anatomopathologie , Plaies par arme blanche/anatomopathologieRÉSUMÉ
A suicidal intoxication of a young woman following an overdose of buflomedil is reported. She died in a hospital 17 hours after ingestion. In various body fluids the following buflomedil concentrations were determined: heart blood 24.5 microg/ml, liquor 21.3 microg/ml, bile 39.1 mg/ml and urine 138.6 mg/ml. Additionally the results of autopsy and histology are presented. Anemia of the internal organs was conspicuous; this finding is attributed to the vasodilating effect of buflomedil on the peripheral vessels.
Sujet(s)
Autopsie , Pyrrolidines/intoxication , Suicide , Adulte , Mauvais usage des médicaments prescrits , Femelle , Humains , Pyrrolidines/sang , Pyrrolidines/urineRÉSUMÉ
Adenosine A (2A) receptors have been implicated in the pathophysiology of schizophrenia by clinical, anatomical, biochemical and genetic studies. We hypothesized that a genetically determined low number of adenosine A (2A) receptors could be a vulnerability factor for the development of the disease. The density of adenosine A (2A) receptors was investigated in human postmortem striatum of patients with schizophrenia (n = 9) and matched controls ( n= 9) using [ H)CGS 21680 as a radioligand probe. The maximum number of binding sites (B) (max) was 70% higher in patients with schizophrenia than in matched controls (609.4 +/- 259.1 354.0 +/- 156.4 fmol/mg protein, p=0.04). No significant difference could be discerned for the affinity of caffeine for adenosine A receptors between patients and controls. The increase in receptor density correlated with the dose of antipsychotic medication in chlorpromazine equivalents (r =0.61, = 0.014). We failed to provide evidence for a genetically determined reduction of adenosine A 2(A) receptors in schizophrenia. Instead, consistent with findings from animal experiments, our observation supports a role of adenosine A (2A) receptors in the molecular effects of antipsychotic drugs.
Sujet(s)
Adénosine/analogues et dérivés , Corps strié/métabolisme , Récepteurs purinergiques P1/métabolisme , Schizophrénie/métabolisme , Adénosine/métabolisme , Sujet âgé , Sujet âgé de 80 ans ou plus , Neuroleptiques/usage thérapeutique , Cadavre , Caféine/métabolisme , Groupes témoins , Femelle , Humains , Mâle , Adulte d'âge moyen , Phénéthylamines/métabolisme , Agonistes des récepteurs purinergiques P1 , Récepteur A2A à l'adénosine , Schizophrénie/traitement médicamenteux , Régulation positiveRÉSUMÉ
BACKGROUND: Patients with Parkinson disease characteristically exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography, a new neuroimaging technique. The same echo feature of the SN can be identified in 9% of healthy adults. OBJECTIVE: To evaluate the relevance of the echogenic SN in healthy adults. DESIGN: In the first part of the study, 10 healthy subjects younger than 40 years with a distinct SN hyperechogenicity underwent extensive neurological, motor, neuropsychological, and fluorine 18-dopa positron emission tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10 subjects with a low echogenic SN. In the second part of the study, the postmortem brains of 20 patients without extrapyramidal disorders during their lifetime were sonographically examined with a particular focus on SN echogenicity. Subsequently, one half of the brain was prepared for heavy metal analysis, the other for a histological examination. RESULTS: Healthy subjects with SN hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake, especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right side, P =.009), whereas their neuropsychological and motor performance were normal. Postmortem studies showed that the echogenicity of the SN correlated with its iron content. CONCLUSIONS: Increased echogenicity of the SN, characteristically seen in Parkinson disease, is related to a functional impairment of the nigrostriatal system (even in young healthy adults) that can be revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related to a higher tissue iron level, which is known to enhance the cells' generation of reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography may identify a susceptibility marker for the development of nigral injury that can be detected early in life, prior to the onset of Parkinson disease.