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Biomedical subjects

R Seidl

Publications and source records attributed to R Seidl.

At least 37 records · Page 2Linked to original sources

A taurine and caffeine-containing drink stimulates cognitive performance and well-being.

Caffeine- and taurine-containing drinks have been on the European market for about a decade, and research on the individual constituents of these drinks indicates an improvement in cognitive performance resulting from consumption of such drinks. In this double-blind, placebo-controlled study using 10 graduate students, we obtained the P300 components of event-related potential (ERP) waveforms following an auditory oddball paradigm, measured motor reaction time, and applied the d2 test for the assessment of attention. Status of mood was assessed by the "Basler-Befindlichkeitsbogen" questionnaire, a standard test for evaluation of feelings of well-being. Measurements were made at night, prior to and starting one hour after consumption of energy drink ingredients or placebo. At the end of the experiment (midnight), P300 latency and motor reaction time were significantly longer compared with baseline measurements in the placebo group, but were unchanged in the energy drink group. In the test system for evaluating feelings of well-being, total scores, vitality scores and social extrovertedness scores were significantly decreased in the placebo group but not in the energy drink group. The findings clearly indicate that the mixture of three key ingredients of Red Bull Energy Drink used in the study (caffeine, taurine, glucuronolactone) have positive effects upon human mental performance and mood. These effects may be mediated by the action of caffeine on purinergic (adenosinergic) receptors and taurine modulation of receptors. As half of the study cohort were non-caffeine users, the described effects cannot be explained in terms of the restoration of plasma caffeine levels to normal following caffeine withdrawal.

Adult↗

Long term neurological and behavioral effects of graded perinatal asphyxia in the rat.

Perinatal hypoxic-ischemic states can cause irreversible damage to the brain, ranging from minimal brain dysfunction to death. Only few studies have been reported describing neurological, cognitive and behavioral deficits following perinatal asphyxia. We therefore decided to study long term effects of perinatal asphyxia in a well-documented animal model resembling the clinical situation. Caeserean section in rats was performed and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 5-20 min; pups were then given to surrogate mothers and examined at three month of age. Examinations consisted of a battery of motor and reflex tests, Morris water maze, multiple T-maze, elevated plus maze and open field studies. No abnormalities were found in rats even with long periods of perinatal asphyxia by neurological examination, in the open field and in mazes. Interestingly, in the elevated plus maze rats with long lasting exposure to hypoxia (15 and 20 min of asphyxia) showed reduced anxiety-related behavior. This finding may be relevant for the explanation of anxiety related disorders in adulthood with a tentative history in the perinatal period.

Animals↗

Prolonged generalized epileptic seizures triggered by breath-holding spells.

We report a 3-year-old female with anoxic-epileptic seizures. Beginning at 11 months of age, she had repeated breath-holding spells with transition into generalized tonic-clonic seizures or status epilepticus. Interictal electroencephalography exhibited no abnormalities. A multidisciplinary diagnostic approach revealed a severely disturbed mother-daughter relationship that was the trigger of the breath-holding spells. Psychotherapy for the mother and daughter led to cessation of the breath-holding spells and, consequently, of the anoxic-epileptic seizures. Her further development was largely normal. We discuss the etiology and treatment of anoxic-epileptic seizures. This case is the first reported case of anoxic epileptic seizures that responded to psychologic rather than antiepileptic treatment. We advocate an initial psychologic assessment to help determine the appropriate treatment in children with recurrent anoxic-epileptic seizures.

Apnea↗

Familial idiopathic West syndrome.

Two families, each with occurrence of West syndrome in two siblings, are presented. Monozygotic twins in family 1 developed infantile spasms at the age of 4 months. Two female siblings in family 2 started to have seizures at the age of 6 months, but 2 years apart. The family history; development prior to West syndrome; clinical, electroencephalographic, and neuroradiologic findings; diagnostic work-up; and treatment are described. The outcome in family 1 (follow-up after 2 years) showed no conspicuous findings on physical and neurologic examination, and psychomotor development appropriate to cognitive, motor, and language developmental age in both twins. In family 2 (follow-up after 3 and 5 years), the older sister only was one standard deviation below mean in intellectual developmental age. Simultaneous occurrence of infantile spasms in both siblings from these two families but with variable clinical expression suggests there is a genetic susceptibility and variable phenotypic expression. Long-term follow-up will demonstrate whether these cases may be classified as "familial idiopathic West syndrome."

Adult↗

Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome.

In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer-type. Upregulation of p53 and APO-1/Fas (CD95) precedes apoptosis in many cell types, and a potential role for these molecules has already been demonstrated in Alzheimer's disease (AD) and several other neurodegenerative diseases. We measured p53 and APO-1/Fas (CD95) protein in four different regions of cerebral cortex and cerebellum in nine adult DS patients with Alzheimer-like neuropathologic lesions compared to nine controls. Quantitative ELISA demonstrated higher frontal lobe (mean+/-SD: 0.10+0.035 vs. 0.041+/-0.016 ng/mg protein), temporal lobe (0.062+/-0.021 vs. 0.032+/-0.019 ng/mg protein) and cerebellar levels (0.078+/-0.030 vs. 0.039+/-0.032 ng/mg protein) of p53 protein, and higher temporal lobe (mean+/-SD: 12.3+/-4.3 vs. 5.3+/-2.0 U/mg protein) and cerebellar levels (5.9+/-1.4 vs. 2.9+/-1.1 U/mg protein) of APO-1/Fas (CD95) protein. The results suggest that p53- or APO-1/Fas (CD95)-associated apoptosis may be an important feature of neurodegeneration in DS.

Adult↗

[An adult patient with phenylketonuria before and one year after reinstitution of diet therapy].

BACKGROUND: In phenylketonuria (PKU) a phenylalanine restricted diet during the first years of life can prevent the development of severe cognitive damage. OBJECTIVE: Could neuropsychological or neurological changes occur in a 20-year-old patient with PKU (diagnosed early and treated until the age of 8 years) after 12 years of normal nutrition and if so, can these changes be counteracted by reinstitution of a low phenylalanine diet? METHODS: Psychological (intelligence, attention), neurophysiological (evoked potentials) and neuroradiological examination (magnetic resonance tomography [MRT] of the brain) were performed before and after one year of treatment with a diet low in phenylalanine. RESULTS: During the reinstitution of dietary therapy we observed significant improvements in attentiveness (percentage increase of 30), whereas intelligence subtests remained stable, a reduction in hyperreflexia, shortening of the latencies of the evoked potentials and a decrease in periventricular pathological signal alterations as evaluated by MRT. CONCLUSIONS: The reintroduction of a diet low in phenylalanine improved psychological and neurological symptoms in this PKU patient. We recommend a constant low-phenylalanine diet throughout life in patients with PKU.

Adult↗

Serotonin (5-HT) in brains of adult patients with Down syndrome.

Down syndrome (DS) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. Furthermore, non-cognitive symptoms may be a cardinal feature of functional decline in adults with DS. As the serotonergic system plays a well known role in integrating emotion, cognition and motor function, serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) were investigated in post-mortem tissue samples from temporal cortex, thalamus, caudate nucleus, occipital cortex and cerebellum of adult patients with DS, Alzheimer's disease (AD) and controls by use of high performance liquid chromatography (HPLC). In DS, 5-HT was found to be age-dependent significantly decreased in caudate nucleus by 60% (DS: mean +/- SD 58.6 +/- 28.2 vs. Co: 151.7 +/- 58.4 pmol/g wet tissue weight) and in temporal cortex by about 40% (196.8 +/- 108.5 vs. 352.5 +/- 183.0 pmol/g), insignificantly reduced in the thalamus, comparable to controls in cerebellum, whereas occipital cortex showed increased levels (204.5 +/- 138.0 vs. 82.1 +/- 39.1 pmol/g). In all regions of DS samples, alterations of 5-HT were paralleled by levels of 5-HIAA, reaching significance compared to controls in thalamus and caudate nucleus. In AD, 5-HT was insignificantly reduced in temporal cortex and thalamus, unchanged in cerebellum, but significantly elevated in caudate nucleus (414.3 +/- 273.7 vs. 151.7 +/- 58.4 pmol/g) and occipital cortex (146.5 +/- 76.1 vs. 82.1 +/- 39.1 pmol/g). The results of this study confirm and extend putatively specific 5-HT dysfunction in basal ganglia (caudate nucleus) of adult DS, which is not present in AD. These findings may be relevant to the pathogenesis and treatment of cognitive and non-cognitive (behavioral) features in DS.

Adult↗

Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome.

In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic early mental retardation and precocious neurodegeneration of Alzheimer-type. The human IAP (inhibitor of apoptosis proteins) genes (NAIP, c-IAP-2/HIAP-1, c-IAP-1/Hiap-2, XIAP, survivin) are an evolutionary conserved family of proteins which prevent cell death across species, implying that they act at a central, highly conserved point in the cell death cascade. Evidence for downregulation of NAIP-mRNA in fetal DS (23rd week of gestation), as found by subtractive hybridization technique challenged studies at the protein level in adult DS brain specimen. NAIP-like immunoreactivity was determined in four different regions of cerebral cortex and cerebellum in 9 adult DS patients with Alzheimer-like neuropathologic lesions, 9 Alzheimer disease (AD) patients as compared to 9 controls. For the first time, NAIP-IR could be demonstrated in different cortical regions of the human brain. Compared to control subjects, western blotting demonstrated significantly decreased levels in parietal and occipital cortex in DS and in frontal and occipital cortex in AD. While the mode of NAIP action is unknown, inhibition of certain caspases has already been demonstrated for other IAP-family members (c-IAP1, c-IAP2 and XIAP). Although decreased NAIP-IR of certain brain regions in DS and AD awaits further confirmation, the results suggest that alterations of apoptosis regulatory (inhibitory) proteins may be another feature of neurodegeneration in DS and AD.

Adult↗

Heat-shock protein 70 levels in brain of patients with Down syndrome and Alzheimer's disease.

Heat-shock proteins are proteins serving as molecular chaperones, involved in the protection of cells from various forms of stress. Since the expression of these proteins is closely related to that of amyloid precursor protein (APP), heat-shock protein has been studied in brain of patients with Alzheimer's disease (AD) and furthermore, brain Hsp70 mRNA levels were related to the agonal state. The aim of our study was to demonstrate the presence of Hsp70--immunoreactive protein in brain of controls, patients with AD and Down Syndrome (DS) in individual brain regions. The rationale for the study was to test the hypothesis that expression of Hsp70, a protein involved in apoptosis would be altered in brain of these patients with neurodegenerative disorders where (neuronal) apoptosis is a hallmark of the disease. Brain immunoreactive-Hsp70--protein (Hsp70) was determined by Western blotting using specific monoclonal antibody in five different brain regions (frontal, parietal, occipital, temporal cortex and cerebellum) from controls, DS and AD patients. Hsp70 expression was significantly increased in temporal cortex of patients with AD (arbitrary units: means +/- SD; 0.35 +/- 0.49 for controls, 0.97 +/- 0.70 for DS patients, 1.16 +/- 0.56 for AD patients). In frontal and parietal cortex from DS patients, there was a strong correlation between Hsp70 levels and the length of post-mortem interval (r = 0.95, P < 0.01 and r = 0.82, P < 0.021).

Alzheimer Disease↗

Latex sensitization in spina bifida appears disease-associated.

OBJECTIVE: The high prevalence of latex sensitization (up to 80%) in patients with spina bifida (SB) has been attributed to repeated exposure to latex products, whereas disease-associated factors have not been considered. METHODS: We compared children with SB (n = 21) and children with posthemorrhagic or congenital hydrocephalus (PH, n = 32), all of whom had a ventriculoperitoneal shunt since young age. Latex sensitization, number of operations, atopic history, and total IgE levels were evaluated. RESULTS: The following characteristics were recorded: age (SB: 52 months, range 1 to 264 months; PH: 71 months, range 1 to 192 months) and mean number of operations (SB: 2. 09; PH: 2.53). Of the SB group, 43% (9 of 21) showed elevated latex-specific IgE antibodies in contrast to 6% (2 of 32) in the PH group (P <.01). Latex-specific IgE antibodies were detected by 1 year of age, and one surgical operation was sufficient to induce latex-specific IgE-antibody production in patients with SB. CONCLUSIONS: The results suggest that the SB population bears a disease-associated propensity for latex sensitization. Sensitization to latex antigens may occur after the very first contact, arguing for latex avoidance measures from the very beginning of life.

Adolescent↗

Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride.

Nephrogenic diabetes insipidus (NDI) is characterised by the inability of the kidney to concentrate urine in response to arginine vasopressin. The consequences are severe polyuria and polydipsia, often associated with hypertonic dehydration. Intracerebral calcification, seizures, psychosomatic retardation, hydronephrosis, and hydroureters are its sequelae. In this study, four children with NDI were treated with 3 mg/kg/day hydrochlorothiazide and 0.3 mg/kg/day amiloride orally three times a day for up to five years. While undergoing treatment, none of the patients had signs of dehydration or electrolyte imbalance, all showed normal body growth, and there was no evidence of cerebral calcification or seizures. All but one had normal psychomotor development and normal sonography of the urinary tract. However, normal fluid balance was not attainable (fluid intake, 3.8-7.7 l/m2/day; urine output, 2.2-7.4 l/m2/day). The treatment was well tolerated and no side effects could be detected. Prolonged treatment with hydrochlorothiazide/amiloride appears to be more effective and better tolerated than just hydrochlorothiazide. Its efficacy appears to be similar to that of hydrochlorothiazide/indomethacin but without their severe side effects.

Amiloride↗

Development of solid-phase chemiluminescence immunoassays for digoxin comparing flow injection and sequential injection techniques.

The development of a competitive solid-phase immunoassay for digoxin making use of the acridinium chemiluminescence system is described. Two different instrumental approaches are compared. One is based on a continuous flow system using a peristaltic flow injection analysis pump; the other uses a new sequential injection technique. In both systems a flow cell, consisting of transparent PTFE tubing packed with immobilized antibodies, acts as an immunoreactor. The entire assay, including both the immunoreaction and the chemiluminescence reaction, takes place in this immunoreactor cell. Compared with the flow injection technique, the sequential injection mode showed higher precision, ranging from 2.16 to 5.5% RSD depending on concentration. The total assay time, including regeneration, is less than 8 min with the sequential injection technique. The detection limit for both techniques is in the low femtomole range.

Cardiotonic Agents↗

Evidence against increased oxidative DNA-damage in Down syndrome.

In Down syndrome (DS), oxidative DNA-damage may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer type. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (8-OHdG), in nuclear DNA (nDNA) isolated from four different regions of cerebral cortex and cerebellum in 10 adult DS and 10 Alzheimer's disease (AD) patients compared to normal controls. Levels of 8-OHdG in post-mortem brain tissue were investigated by means of high-performance liquid chromatography with electrochemical detection. There was no significant increase in DS and AD compared to controls in any of the brain regions. Highest amounts of 8-OHdG were in temporal cortex in DS (180.0 +/- 9.6 nmol/g wet weight tissue), AD (172.4 +/- 14.6 nmol/g wet weight tissue) and controls (183.4 +/- 12.7 nmol/g). We conclude that the results provide evidence against an increased reactive oxygen species (ROS) induced damage to nDNA in DS and AD.

8-Hydroxy-2'-Deoxyguanosine↗

Evidence against increased glycoxidation in patients with Alzheimer's disease.

Neuropathological findings of Alzheimer's disease (AD) are intracellular (neurofibrillary tangles) and extracellular (senile plaques) filamentous protein aggregates. Non-enzymatic glycation has been proposed as a primary factor in this pathogenesis, leading to increased insolubility of tau protein and beta-amyloid. The aim of our study was to test the hypothesis that increased glycoxidation, i.e. increased levels of oxidized products from non-enzymatic glycation could be found in brains of patients with AD and of aged Down syndrome (DS) subjects with abundant AD-like neuropathological lesions. Frontal cortex specimens were assayed for pentosidine (Pent) and N-epsilon-carboxymethyl-lysine (CML) by reversed phase high performance liquid chromatographical methods. Pent and CML levels in AD (n = 10; Pent, 35.5 +/- 4.84 mumol/g wet-weight tissue; CML, 135.2 +/- 5.0 mumol/g wet-weight tissue) were comparable to DS (n = 9; Pent, 36.4 +/- 3.21; CML, 133.5 +/- 4.7) and controls (n = 10; Pent, 35.2 +/- 3.55; CML, 136.9 +/- 3.3). We conclude that the results are not compatible with the concept of increased glycoxidation in AD compared to normal aging.

Aged↗

Auditory evoked potentials in young patients with Down syndrome. Event-related potentials (P3) and histaminergic system.

Subjects with Down syndrome exhibit various types of cognitive impairment. Besides abnormalities in a number of neurotransmitter systems (e.g. cholinergic), histaminergic deficits have recently been identified. Brainstem auditory evoked potentials (BAEPs) and auditory event-related potentials (ERPs), were recorded from 10 children (aged 11-20 years) with Down syndrome and from 10 age- and sex-matched healthy control subjects. In Down subjects, BAEPs revealed shortened latencies for peaks III and V with shortened interpeak latencies I-III and I-V. ERPs showed a delay of components N1, P2, N2 and P3. In addition, subjects with Down syndrome failed to show P3 amplitude reduction during repeated stimulation. To evaluate the cognitive effects of histaminergic dysfunction, ERPs were recorded from 12 healthy adults (aged 20-28 years) before and after antihistaminergic intervention (pheniramine) compared to placebo. Whereas components N1, P2, N2 remained unchanged after H1-receptor antagonism, P3 latency increased and P3 amplitude showed no habituation in response to repeated stimulation. The results suggest that the characteristic neurofunctional abnormalities present in children with Down syndrome must be the consequence of a combination of structural and neurochemical aberrations. The second finding was that antihistaminergic treatment affects information processing tested by ERPs similar to that seen with anticholinergic treatment.

Adolescent↗

The effect of behavioural states on cerebral oxygenation during endotracheal suctioning of preterm babies.

Near infrared spectroscopy (NIRS) was used to investigate the effect of behavioural states on changes of oxygenated (O2Hb), deoxygenated haemoglobin (HHb) and total haemoglobin (tHb), during endotracheal suctioning. In an open prospective design, NIRS measurements have been done during 20 suctioning episodes in 13 preterm neonates. Heart rate, arterial oxygen saturation, and carbon dioxide tension were monitored continuously. Behavioural state (BS) observations were made and documented as well. The statistical analysis showed that in patients who were active, with crying periods during suctioning (behavioural states 4-5), changes of oxygenated (p < 0.005) and deoxygenated haemoglobin (p < 0.05), as well as of arterial oxygen saturation (p < 0.05) and heart rate (p < 0.05) were significantly greater than in patients who were quiet with predominant behavioural state 1, 2 and 3. These results underline the influence of behavioural states on the physiological answers to endotracheal suctioning. NIRS proved to be a valuable tool to evaluate possible harmful effects of different suctioning techniques.

Cerebrovascular Circulation↗

Polyamines in frontal cortex of patients with Down syndrome and Alzheimer disease.

Polyamines may play an important role in brain development, mature brain function and also in neurodegenerative conditions. We investigated polyamine levels in frontal cortex of human post-mortem brain samples of elderly patients with Down syndrome (DS), Alzheimer disease (AD) and normal controls by means of chromatographic separation after dansylation. Spermidine and spermine concentrations were markedly decreased in DS and AD. Polyamine levels were neither related to age and post-mortem interval nor to choline acetyltransferase activity, as indicator of neuronal loss. Our results support the idea that besides other neurotransmitter systems, endogenous polyamine levels are altered in dementing illnesses such as Alzheimer disease and Down syndrome.

Aged↗