Fatal visit to the general practitioner.

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.

Neuron-specific alterations in signal transduction pathways associated with Alzheimer's disease.

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.

Fatal visit to the dentist.

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.

Neuron-specific mitochondrial DNA deletion levels in sporadic Alzheimer's disease.

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.

Can enzyme kinetics of prooxidants teach us a lesson about the treatment of Alzheimer's disease: a pilot post-mortem study.

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.

Increased xanthine oxidase in the thalamus and putamen in depression.

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.

Increased activity of mitochondrial aldehyde dehydrogenase (ALDH) in the putamen of individuals with Alzheimer's disease: a human postmortem study.

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).

Identification of L-ferritin in neuromelanin granules of the human substantia nigra: a targeted proteomics approach.

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.

Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder: a comparative post-mortem study.

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).

The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI-A binding site in human hippocampus.

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).

Digital imaging of the dissection and sexual abuse of a corpse - an exceptional case of necrophilia.

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.

Increased brain levels of 4-hydroxy-2-nonenal glutathione conjugates in severe Alzheimer's disease.

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).

Early impairment in dopaminergic neurotransmission in brains of SIV-infected rhesus monkeys due to microglia activation.

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.

"Subcellular proteomics" of neuromelanin granules isolated from the human brain.

"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.

Cuts to the offender's own hand--unintentional self-infliction in the course of knife attacks.

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.

Up-regulation of striatal adenosine A(2A) receptors in schizophrenia.

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.

Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury.

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.