Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
Add more filters










Publication year range
1.
Int J Legal Med ; 126(5): 765-71, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22752751

ABSTRACT

Accidents constitute one of the greatest risks to children, yet there are few medical reports that discuss the subject of accidental asphyxia. However, a systematic analysis of all documented cases in Germany over the years 2000-2008 has now been conducted, aiming at identifying patterns of accidental asphyxia, deducing findings, defining avoidance measures and recommending ways of increasing product safety and taking possible precautions. The analysis is based on a detailed retrospective analysis of all 91 relevant autopsy reports from 24 different German forensic institutes. A variety of demographic and morphological data was systematically collected and analysed. In 84 of the 91 cases, the sex of the victim was reported, resulting in a total of 57 boys (68 %) and 27 girls (32 %). The age spread ranged between 1 day and 14 years, with an average of 5.9 years. Most accidents occurred in the first year of life (20 %) or between the ages of 1 and 2 years (13 %). In 46 % of cases, the cause of death was strangulation, with the majority occurring in the home environment. In 31 % of all cases, the cause of death was positional asphyxia, the majority resulting from chest compression. In 23 % of cases, the cause of death was aspiration, mainly of foreign bodies. Today, accidental asphyxiation is a rare cause of death in children in Germany. Nevertheless, the majority of cases could have been avoided. Future incidence can be reduced by implementing two major precautions: increasing product safety and educating parents of potentially fatal risks. Specific recommendations relate to children's beds, toys and food.


Subject(s)
Accidents/legislation & jurisprudence , Asphyxia/pathology , Accidents/mortality , Accidents, Home/legislation & jurisprudence , Accidents, Home/mortality , Accidents, Home/prevention & control , Adolescent , Airway Obstruction/pathology , Airway Obstruction/prevention & control , Asphyxia/mortality , Asphyxia/prevention & control , Autopsy , Cause of Death , Child , Child Day Care Centers , Child, Preschool , Consumer Product Safety/legislation & jurisprudence , Female , Foreign Bodies/pathology , Foreign Bodies/prevention & control , Germany , Hemorrhage/pathology , Humans , Infant , Infant, Newborn , Male , Parents/education , Purpura/pathology , Retrospective Studies , Risk Factors
2.
J Neural Transm Suppl ; (71): 39-43, 2006.
Article in English | MEDLINE | ID: mdl-17447414

ABSTRACT

Oxidative stress has been associated with damage and progressive cell death that occurs in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). The aim of this study was to investigate the antioxidant capacity in postmortem motor cortex (MC), nucleus caudatus (NC), gyrus temporalis (GT) and substantia nigra (SN) from controls (C) and patients with PD and AD. The initial samples consisted of 68 subjects of PD, AD and C. Brains were matched for age, sex and postmortem time. Brain tissue was homogenized in a phosphate buffer pH 7.3 and separated with two-step centrifugation at 15,000rpm for 30 min and 15,000 rpm for 10 min at 4 degrees C. Antioxidant capacity in the supernatants was measured using the oxygen radical absorbance assay (ORAC). The results showed that in the SN of parkinsonian's brain the balance between production of free radicals and the neutralization by a complex antioxidant system is disturbed. No changes in the antioxidant capacity of postmortem MC and NC of parkinsonian's brain in comparison with C were found. In the SN of parkinsonian's brain, antioxidant capacity seems to be lower in comparison with C (p < 0.05). Antioxidant capacity against peroxyl radical showed that MC of AD patients was lower than in the MC of C (p < 0.005). In NC of AD patients the antioxidant capacity against hydroxyl radical was increased in comparison with C (p < 0.04). No changes in the antioxidant capacity were found in brain tissues of AD in comparison with C, when CuSO4 was used as a free radical generator.


Subject(s)
Alzheimer Disease/pathology , Antioxidants/metabolism , Brain/metabolism , Parkinson Disease/pathology , Postmortem Changes , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Analysis of Variance , Brain/pathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Parkinson Disease/metabolism , Spectrophotometry/methods
3.
J Neural Transm (Vienna) ; 111(9): 1191-201, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15338334

ABSTRACT

Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disorders served for control. Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged. Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.


Subject(s)
Brain/enzymology , Oxidative Stress/physiology , Schizophrenia/enzymology , Superoxide Dismutase/metabolism , Adult , Aged , Aged, 80 and over , Antioxidants/metabolism , Brain/physiopathology , Female , Frontal Lobe/enzymology , Frontal Lobe/physiopathology , Humans , Isoenzymes/chemistry , Isoenzymes/metabolism , Male , Middle Aged , Schizophrenia/physiopathology , Substantia Innominata/enzymology , Substantia Innominata/physiopathology , Superoxide Dismutase/chemistry , Up-Regulation/physiology
4.
J Neurovirol ; 10(3): 163-70, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15204921

ABSTRACT

The basal ganglia, structures rich in the neurotransmitter dopamine, are primarily affected during human immunodeficiency virus (HIV) infection. The authors measured levels of dopamine and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, in brains of uninfected and simian immunodeficiency virus (SIV)-infected rhesus monkeys during the asymptomatic stage of the infection. Moreover, the authors investigated changes in cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB), two factors involved in the signaling pathway of dopamine. The brain regions examined were the nucleus accumbens and the corpus amygdaloideum, which are limbic structures of the basal ganglia that are involved in the pathophysiology of psychiatric disorders and substance abuse. Dopamine content was reduced in both regions of SIV-infected monkeys compared to uninfected animals. Moreover, dopamine deficits were associated with a decrease in expression of total CREB. Intracellular concentrations of cAMP were decreased in nucleus accumbens and remained unchanged in corpus amygdaloideum of SIV-infected macaques. Changes in dopamine signaling were not related to pathology or viral load of the investigated animals. The results suggest that dopamine defects precede neurologic deficits and implicate dysfunction of the dopaminergic system in the etiopathogenesis of HIV dementia. Therefore, affective complications in HIV subjects should not be interpreted only as reactive psychological changes. The alterations in the mesolimbic dopaminergic system during asymptomatic stage of SIV infection implicate a biological background for psychiatric disorders in HIV infection.


Subject(s)
Brain/metabolism , Cyclic AMP/metabolism , Dopamine/metabolism , Signal Transduction/physiology , Simian Acquired Immunodeficiency Syndrome/physiopathology , 3,4-Dihydroxyphenylacetic Acid/analysis , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Brain/pathology , Brain/virology , Chromatography, High Pressure Liquid , Cyclic AMP Response Element-Binding Protein/metabolism , Dopamine/analysis , Electrophoresis, Polyacrylamide Gel , Homovanillic Acid/analysis , Homovanillic Acid/metabolism , Immunoblotting , Immunohistochemistry , Macaca mulatta , Simian Acquired Immunodeficiency Syndrome/pathology , Simian Immunodeficiency Virus/physiology
5.
J Neural Transm (Vienna) ; 110(10): 1119-27, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14523624

ABSTRACT

The aim of this study was to compare dopamine receptor binding affinities of all currently approved dopamine receptor agonist treatments for Parkinson's disease (PD) in human brain tissue. Alpha-dihydroergocryptine and lisuride displayed higher comparative affinities (Ki=35.4 and 56.7 nM, respectively) for D1 receptors, than the D1/D2 dopamine agonist pergolide (Ki=447 nM). The second generation non-ergot dopamine receptors agonists pramipexole and ropinirole demonstrated no affinity for D1 receptors at concentrations up to 10(-4) M. The ergoline dopamine agonists cabergoline and lisuride displayed the highest affinities for the D2 receptor (Ki=0.61 and 0.95 nM, respectively). Surprisingly, the second generation non-ergot dopamine receptors agonists pramipexole and ropinirole only weakly inhibited binding to D2 receptors (Ki=79.5 and 98.7 microM, respectively using [3H]spiperone). Interestingly we also found that the affinities of cabergoline (Ki=1.27 nM), lisuride (Ki=1.08 nM) and pergolide (Ki=0.86 nM) for the D3 receptor subtype were comparable to that of pramipexole (Ki=0.97 nM). The present results thus support the hypothesis that the antiparkinsonian effect of dopamine receptor agonists is mediated by a more complex interactions with dopamine receptor subtypes than currently believed.


Subject(s)
Corpus Striatum/metabolism , Dopamine Agonists/metabolism , Receptors, Dopamine/metabolism , Aged , Aged, 80 and over , Autopsy , Dopamine Agonists/therapeutic use , Female , Humans , Male , Middle Aged , Parkinson Disease/drug therapy , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3
6.
J Neural Transm (Vienna) ; 109(5-6): 939-46, 2002 May.
Article in English | MEDLINE | ID: mdl-12111480

ABSTRACT

Two polymorphic dinucleotide repeats separated by a short spacer are localized in the promoter region of the serotonin receptor 2C gene ( HTR2C). One of the repeats was found to be evolutionary conserved between humans and rhesus monkeys. Although promoter-associated microsatellites have previously been shown to regulate expression of different genes, we did not find any significant influence of distinct HTR2C promoter microsatellite alleles on transcriptional efficiency as measured by luciferase activity and receptor availability as assayed by [(3)H]-mesulergine binding. Furthermore, no association of specific alleles with bipolar disorder was found. These results indicate that the HTR2C promoter polymorphism does not contribute significantly to the etiopathogenesis of bipolar disorder in females.


Subject(s)
Biological Evolution , Bipolar Disorder/genetics , Microsatellite Repeats/genetics , Promoter Regions, Genetic/genetics , Receptors, Serotonin/genetics , Aged , Aged, 80 and over , Alleles , Animals , Base Sequence/genetics , Cell Line , Conserved Sequence/genetics , Dinucleotide Repeats , Female , Gene Frequency , Humans , Macaca mulatta , Male , Molecular Sequence Data , Rats , Receptor, Serotonin, 5-HT2C
7.
Neurosci Lett ; 324(1): 49-52, 2002 May 10.
Article in English | MEDLINE | ID: mdl-11983292

ABSTRACT

In recent years, an important role for the pathogenesis of Alzheimer's disease (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product of lipid peroxidation, forms stable adducts with a variety of nucleophilic substituents such as thiols or amino moieties. Here, we report the quantification of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp) using the specific and very sensitive method of 32P-postlabeling of deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the hippocampus, the parietal cortex, and the cerebellum of postmortem brains from patients with AD and age matched controls. Adduct levels were highest in the hippocampus, followed by the cerebellum and parietal cortex irrespective of the disease. Neither age, postmortem delay time, gender, nor the extent of neurofibrillary deposits affected tissue adduct levels in the brain areas examined. Although distinctively present in the human brain, the level of HNE-dGp adducts appears not to be useful as a biomarker for AD.


Subject(s)
Aldehydes/metabolism , Alzheimer Disease/metabolism , Brain Chemistry/physiology , Brain/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Lipid Peroxidation/physiology , Neurons/metabolism , Oxidative Stress/physiology , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Alzheimer Disease/physiopathology , Biomarkers , Brain/pathology , Brain/physiopathology , Cerebellum/metabolism , Cerebellum/pathology , Cerebellum/physiopathology , Female , Hippocampus/metabolism , Hippocampus/pathology , Hippocampus/physiopathology , Humans , Male , Neurofibrillary Tangles/metabolism , Neurofibrillary Tangles/pathology , Neurons/pathology , Parietal Lobe/metabolism , Parietal Lobe/pathology , Parietal Lobe/physiopathology , Plaque, Amyloid/metabolism , Plaque, Amyloid/pathology , Sex Factors
8.
J Neural Transm (Vienna) ; 108(3): 335-47, 2001.
Article in English | MEDLINE | ID: mdl-11341485

ABSTRACT

Immunoreactivities of adenylyl cyclase (AC) type I (AC-I), and basal, forskolin- and Mn2+-stimulated AC activities with or without calcium and calmodulin (Ca2+/CaM) were estimated in temporal cortex (TC)-and nucleus accumbens (NAc) membranes from brains of heroin addicts and controls. Immunoreactivity of AC-I was significantly decreased in TC from brains of heroin addicts, but that did not change in NAc. Ca2+/CaM-sensitive AC activity was significantly lower in TC from brains of heroin addicts, but that activity in NAc did not show significant difference compared with the control. Some previous reports demonstrated that Ca2+/CaM-sensitive AC activity in membranes from postmortem human brain reflected the function of AC-I. Therefore, the downregulation of AC-I in TC plays an important role in the molecular mechanism of chronic opiate addiction in human brain.


Subject(s)
Brain Chemistry/drug effects , Brain/drug effects , Cyclic AMP/metabolism , Heroin Dependence/metabolism , Heroin/adverse effects , Narcotics/adverse effects , Signal Transduction/drug effects , Adenylyl Cyclases/metabolism , Adult , Age Factors , Brain/metabolism , Brain/physiopathology , Brain Chemistry/physiology , Calcium/metabolism , Calcium/pharmacology , Calmodulin/metabolism , Calmodulin/pharmacology , Cell Membrane/drug effects , Cell Membrane/metabolism , Colforsin/metabolism , Colforsin/pharmacology , Female , Freezing , Heroin Dependence/physiopathology , Humans , Immunohistochemistry , Male , Manganese/metabolism , Manganese/pharmacology , Neurons/drug effects , Neurons/metabolism , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Nucleus Accumbens/physiopathology , Signal Transduction/physiology , Subcellular Fractions/drug effects , Subcellular Fractions/metabolism , Temporal Lobe/drug effects , Temporal Lobe/metabolism , Temporal Lobe/physiopathology
9.
Alcohol Clin Exp Res ; 25(5): 717-25, 2001 May.
Article in English | MEDLINE | ID: mdl-11371721

ABSTRACT

BACKGROUND: It is still difficult to define the biochemical mechanisms that cause alterations in neuronal function and plasticity and neuronal cell loss in the brains of alcohol-dependent patients. METHODS: To evaluate the extent of cerebral alcohol-induced oxidative stress ex vivo, we investigated the levels of glutathione (GSH), its oxidation product glutathione disulfide (GSSG, produced by GSH-peroxidases), and the activities of catalase and superoxide dismutases (SOD). In addition, selected brain regions from up to 22 subjects (versus controls) were studied post mortem to compare the amount of oxidized DNA-base 8-hydroxy-2'-deoxyguanosine (8-OHdG) with levels of deoxyguanosine (dG) in mitochondrial and nuclear DNA. RESULTS: The most prominent findings showed significantly decreased GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in the corpus mamillare and cerebellum, which appeared due to an increase in GSSG caused by chronic alcohol intake. Catalase activity was increased in only the frontal cortex, whereas decreased catalase activity was found in the corpus callosum. In contrast, neither copper-zinc-superoxide dismutase (CuZnSOD) and manganese-superoxide dismutase (MnSOD) activities nor 8-OHdG/dG molar ratios were altered, although a tendency toward higher OHdG/dG ratios in temporal and parietal cortex from alcohol-dependent patients could be detected when mitochondrial DNA was analyzed selectively. CONCLUSIONS: We propose that decreased brain GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in alcohol-dependent patients may reflect neural impairment due to increased peroxide production after chronic alcohol consumption. However, future experiments, investigating the activities of enzymes and cofactors involved in GSH synthesis and metabolism in the human brain, will have to validate the specificity of these results for oxidative stress.


Subject(s)
Alcoholism/metabolism , Brain/metabolism , Deoxyguanosine/metabolism , Glutathione Disulfide/metabolism , Glutathione/metabolism , Oxidative Stress/physiology , 8-Hydroxy-2'-Deoxyguanosine , Aged , Aged, 80 and over , Alcoholism/pathology , Brain/pathology , Catalase/metabolism , DNA, Mitochondrial/metabolism , Deoxyguanosine/analogs & derivatives , Female , Humans , Male , Middle Aged , Statistics, Nonparametric , Superoxide Dismutase/metabolism
10.
Neuroreport ; 11(11): 2391-3, 2000 Aug 03.
Article in English | MEDLINE | ID: mdl-10943691

ABSTRACT

HIV infection at late stages is associated with neurological complications including impaired motor and cognitive functions. We used simian immunodeficiency (SIV)-infected rhesus monkeys, an animal model of HIV infection, to investigate changes in choline acetyltransferase (ChAT) activity, a biochemical marker of cognitive function, in post-mortem brains during early, asymptomatic SIV infection and AIDS. ChAT activity was dramatically reduced in putamen and hippocampus already during asymptomatic infection. In animals with AIDS, ChAT activity was further decreased. The reduction of ChAT was not related to brain viral load or CNS pathological lesions. Our results demonstrate deficits in ChAT activity already during the first months of SIV infection and imply that cognitive dysfunction may occur early in immunodeficiency viral infections.


Subject(s)
AIDS Dementia Complex/metabolism , Brain/metabolism , Choline O-Acetyltransferase/metabolism , Neurons/metabolism , Simian Acquired Immunodeficiency Syndrome/metabolism , Simian Immunodeficiency Virus/metabolism , AIDS Dementia Complex/pathology , AIDS Dementia Complex/physiopathology , Animals , Biomarkers/analysis , Brain/pathology , Brain/physiopathology , Brain/virology , Disease Models, Animal , Hippocampus/metabolism , Hippocampus/pathology , Hippocampus/physiopathology , Hippocampus/virology , Macaca mulatta/anatomy & histology , Macaca mulatta/metabolism , Neurons/pathology , Neurons/virology , Prognosis , Putamen/metabolism , Putamen/pathology , Putamen/physiopathology , Putamen/virology , Simian Acquired Immunodeficiency Syndrome/pathology , Simian Acquired Immunodeficiency Syndrome/physiopathology , Time Factors , Viral Load/statistics & numerical data
11.
Neurosci Lett ; 287(2): 109-12, 2000 Jun 23.
Article in English | MEDLINE | ID: mdl-10854724

ABSTRACT

The density of nicotinic alpha4beta2 receptors, which are believed to largely mediate nicotine's effects, has been reported to be decreased in post-mortem hippocampus of patients with schizophrenia. In the present study, using [(3)H]cytisine as a radioligand, we observed a significant 30% decrease in post-mortem striatum of patients with schizophrenia (n=12) as compared to controls (n=12). A 25% decrease of striatal alpha4beta2 receptor density in patients with Parkinson's syndrome (n=12) was not significant. As an upregulation of alpha4beta2 receptors has been observed due to nicotine consumption, the beneficial effects of nicotine described in patients with schizophrenia may be partly due to a compensation for a decrease in alpha4beta2 nicotinic acetylcholine receptors.


Subject(s)
Corpus Striatum/metabolism , Parkinson Disease/metabolism , Receptors, Nicotinic/metabolism , Schizophrenia/metabolism , Aged , Aged, 80 and over , Alkaloids , Azocines , Corpus Striatum/chemistry , Female , Humans , Male , Middle Aged , Parkinson Disease/pathology , Quinolizines , Radioligand Assay , Receptors, Nicotinic/analysis , Schizophrenia/pathology , Tritium
SELECTION OF CITATIONS
SEARCH DETAIL
...