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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects (1997)
    Springer
    European journal of clinical pharmacology 51 (1997), S. 493-498 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Cardiovascular effects; pharma-cokinetics ; healthy volunteers ; obese subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of a single i.v. dose of the new racemic β-adrenoceptor-blocker nebivolol [0.073 mg base · kg–1 ideal body weight (IBW)] was studied in 9 obese (157% IBW) and 9 non-obese healthy volunteers (98% IBW). Each group contained 4 men and 5 women, aged 32 years, including one poor hydroxylator (dextrometorphan test). Methods: The cardiovascular effects of nebivolol are significant decreases in systolic and diastolic blood pressure, heart rate and cardiac output, which last up to 4–5 h. The plasma concentrations of the separate d- and l- enantiomers of nebivolol, with and without hydroxylated metabolite, were measured by radioimmunoassay and the unchanged racemate by high-pressure liquid chromatography (HPLC). The pharmacokinetic parameters for each form were calculated separately. Results: The main pharmacokinetic parameters of unchanged nebivolol in extensive metabolizers were (controls): distribution volume at steady state (Vss) 673 l; volume corrected by real body weight (Vss · kg–1) 11.2 l ·  kg–1; total clearance (CL) 51.6 h–1; and terminal half-life (t1/2) 10.3 h. The Vss (898 l) and CL (71.6 l · h–1) were significantly higher in obese patients. But Vss · kg–1 (9.4 l · kg–1) and t1/2 (10.0 h) were not significantly different from those in controls. The CL was clearly reduced (15–18 l · h–1) and the t1/2 prolonged (32–34 h) in poor hydroxylators, in both control and obese subjects. The pharmacokinetic parameters of the separate unchanged enantiomers were similar to those of the racemate in both groups. The pharmacokinetics of l-nebivolol were more influenced by the hydroxylation phenotype than those of d-nebivolol. The trend of the results for the sum of each enantiomer plus its metabolite, was similar to those for the unchanged form. Conclusion: The distribution of nebivolol in the adipose tissue in obese subjects is limited, despite its high lipophilicity. The differences between obese and non-obese subjects were not clinically relevant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050237
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  • 2
    Electronic Resource
    Electronic Resource
    Apolipoprotein E, Plaques, Tangles and Cholinergic Dysfunction in Alzheimer's Disease (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Apolipoprotein E is a plasma cholesterol and phospholipid transporter which plays a central role in lipoprotein metabolism in the brain. Apolipoprotein E is a polymorphic protein with three common alleles in the general population, designated ε2, ε3 and ε4 coding for proteins ApoE2, ApoE3 and ApoE4, respectively. Recent findings have demonstrated a significant relationship between the ε4 allele and late onset familial and sporadic Alzheimer's disease. We examined several classical neuropathological hallmarks of Alzheimer's disease to determine whether they might be related to apolipoprotein E genotype: the presence of intracellular neurofibrillary tangles, extracellular senile plaques, and the attenuation of choline acetyltransferase activity. Significant correlations were found between ε4 allele copy number and senile plaque density in the frontal, parietal and fusiform cortical areas. Similarly, significant correlations were also found with increased neurofibrillary tangle number in the frontal and fusiform cortex. Interestingly, there was an inverse correlation between the ε4 allele with temporal cortical choline acetyltransferase activity. To further define the specific function of ApoE4, cultured rat hippocampal neurons were used to investigate interactions involving β-amyloid protein. In this model, ApoE4 (but not ApoE2) was able to reverse the neuroprotective effects of β-amyloid. ApoE3 was demonstrated to increase the internalization of β-amyloid peptide into these neurons. Taken together, these results support the involvement of ApoE4 in the pathogenesis of Alzheimer's disease and also provide some explanations for the possible function of this protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb34415.x
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  • 3
    Electronic Resource
    Electronic Resource
    Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein (1997)
    [s.l.] : Nature Publishing Group
    Nature 387 (1997), S. 500-505 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Transgenic mice were produced by using a construct containing an APP complementary DNA fragment encoding amino acids 591 to 695, which spans the amyloid-forming portion and the carboxy terminus of the human amyloid precursor protein, cloned into the first exon of the human neurofilament NF-L gene ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/387500a0
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of MPTP and l-Deprenyl on Antioxidant Enzymes and Lipid Peroxidation Levels in Mouse Brain (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 65 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). However, it is unclear if altered antioxidant enzyme activity is sufficient to increase lipid peroxidation in PD. We therefore investigated if MPTP can alter the activity of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) and the level of lipid peroxidation. l-Deprenyl, prior to MPTP administration, is used to inhibit MPP+ formation and its subsequent effect on antioxidant enzymes. MPTP induced a threefold increase in SOD activity in the striatum of C57BL/6 mice. No parallel increase in GSH-PX or CAT activities was observed, while striatal lipid peroxidation decreased. At the level of the substantia nigra (SN), even though increases in CAT activity and reduction in SOD and GSH-PX activities were detected, lipid peroxidation was not altered. Interestingly, l-deprenyl induced similar changes in antioxidant enzymes and lipid peroxidation levels, as did MPTP. Taken together, these results suggest that an alteration in SOD activity, without compensatory increases in CAT or GSH-PX activities, is not sufficient to induce lipid peroxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.65062725.x
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  • 5
    Electronic Resource
    Electronic Resource
    Increased Levels of Apolipoprotein D in Cerebrospinal Fluid and Hippocampus of Alzheimer's Patients (1998)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 71 (1998), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Apolipoprotein D (apoD) is a member of the lipocalin family of proteins. Most members of this family are transporters of small hydrophobic ligands, although in the case of apoD, neither its physiological function(s) nor its putative ligand(s) have been unequivocally identified. In humans, apoD is expressed in several tissues, including the CNS, and its synthesis is greatly increased during regeneration of rat peripheral nerves. As apoD may have an important function in the nervous system and, particularly, in nerve regeneration, we measured immunoreactive apoD levels in the hippocampus and in CSF of patients with either Alzheimer's disease (AD) or other neuropathologies. In parallel, we determined the concentrations of apolipoprotein E (apoE), another apolipoprotein also implicated in nerve regeneration and in the etiology of AD. Levels of apoD but not apoE were increased in the hippocampus of AD patients compared with controls. ApoD concentrations, as determined by radioimmunoassay, were significantly increased in the CSF of AD patients (4.23 ± 1.58 µg/ml) and patients with other pathologies (3.29 ± 1.35 µg/ml) compared with those in the CSF of normal subjects (1.15 ± 0.71 µg/ml). Although the differences were smaller than for apoD, the mean apoE concentrations in the CSF of both groups of patients were also significantly higher than those of controls. In AD patients, apoD, but not apoE, levels in CSF and hippocampus increased as a function of inheritance of the ε4 apoE allele. This study therefore demonstrates that increased apoD levels in the hippocampus and in CSF are a marker of neuropathology, including that associated with AD, and are independent of apoE concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1998.71041643.x
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  • 6
    Electronic Resource
    Electronic Resource
    Contribution of technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy to the diagnosis of diabetic foot infection (1998)
    Springer
    European journal of nuclear medicine 25 (1998), S. 132-138 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Bone ; Diabetic foot ; Infection ; Leucocyte scintigraphy ; Technetium-99m
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We conducted a prospective study in order to evaluate the contribution of technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocyte scintigraphy to the diagnosis and follow-up of osteomyelitis in the diabetic foot. The study was conducted between October 1992 and November 1996 and included 42 patients (30 men and 12 women; mean age 63 years) with diabetes mellitus (type 1, n = 22, type 2, n = 20) who had a total of 56 diabetic foot ulcers. The initial exploration included standard radiography, three-phase bone scintigraphy and 99mTc-HMPAO labelled leucocyte scintigraphy (HMPAO-LS), performed within a 3-day interval. For the 56 ulceration sites, 26 cases of osteomyelitis were diagnosed: ten on the basis of radiographic and histological/bacteriological criteria after bone biopsy, 11 after radiographic follow-up and five on the basis of biopsy results alone. No osteomyelitis was present at 30 sites, there were seven cases of cellulitis. The sensitivity and specificity of 99mTc-HMPAO-LS were 88.4% and 96.6% respectively (23 true-positives, 29 true-negatives, one false-positive, three false-negatives). The accuracy of radiography, 99mTc-methylene diphosphonate and HMPAO-LS was 69.6%, 62.5%, and 92.9%, respectively. Follow-up scintigraphy (n = 14) 4 months after initial diagnosis and 1 month after antibiotic withdrawal confirmed cure of osteomyelitis despite the absence of complete clinical regression of the ulcers. In conclusion, 99mTc-HMPAO labelled leucocyte scintigraphy was found to be an excellent method for the diagnosis of osteomyelitis in the diabetic foot. It can contribute to follow-up, particularly when clinical regression of perforating ulcers is incomplete and cure of osteomyelitis must be confirmed in order that antibiotic treatment may be discontinued.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050205
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  • 7
    Electronic Resource
    Electronic Resource
    On power-law kinetics of transport phenomena in minerals (1997)
    Springer
    Physics and chemistry of minerals 24 (1997), S. 495-499 
    Details
    ISSN: 1432-2021
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract  Power laws can be written which describe many physical phenomena in materials and can be of great utility. However, they can sometimes provide a false picture of a relationship between two variables when dependence on a third parameter is not taken into account. (For example, electrical conductivity, diffusion, and creep can be shown to have a spurious power-law dependence on oxygen fugacity if the dependence of activation energy on oxygen fugacity is not considered). Extrapolations of data with such spurious power-law dependences can provide a false picture of material behavior under in-situ conditions in the Earth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002690050064
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  • 8
    Electronic Resource
    Electronic Resource
    Dislocations in CaTiO3 perovskite deformed at high-temperature: a transmission electron microscopy study (1996)
    Springer
    Physics and chemistry of minerals 23 (1996), S. 337-344 
    Details
    ISSN: 1432-2021
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract Dislocation configurations in natural single crystals of CaTiO3 perovskite deformed in high-temperature creep were examined and characterized by transmission electron microscopy. Screw dislocations with Burgers vector [100]pc and [011]pc, dissociated on the $$(01\bar 1)_{{\text{pc}}} $$ plane, form rectangular networks with extended four-fold nodes in the shape of octagons, a configuration never observed in any of the previously investigated perovskites, except CaGeO3. Screw dislocations with Burgers vector [101]pc and $$(\bar 101)_{{\text{pc}}} $$ , on the (010)pc plane, react to form a twist wall; the dislocations with Burgers vector [002] produced by the reaction decompose into two perfect dislocations [001]pc. This results in a new configuration, never observed before, with three-fold nodes at the corners of rectangles. Both the octagonal extended nodes and the junctions decomposed into perfect dislocations are seen in samples deformed indifferently by slip on {100}pc or {110}pc planes, but they seem to appear only above 1520 K, in the cubic phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199499
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  • 9
    Electronic Resource
    Electronic Resource
    Distinguishing lacunar infarcts from dilatations of the perivascular space (1998)
    Springer
    Journal of neurology 245 (1998), S. 813-814 
    Details
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050293
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  • 10
    Electronic Resource
    Electronic Resource
    Dependence on pressure of conduction by hopping of small polarons in minerals of the Earth's lower mantle (1999)
    Springer
    Physics and chemistry of minerals 27 (1999), S. 81-87 
    Details
    ISSN: 1432-2021
    Keywords: Key words Electrical conductivity ; Polarons ; Hopping ; Pressure ; Lower mantle ; Perovskite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract Electrical conductivity of the lower mantle-like assemblage (Mg,Fe)SiO3 perovskite-(Mg,Fe)O magnesiowüstite is usually analyzed using the quasi-chemical Arrhenian approach of diffusion. The conductivity of this assemblage has often been attributed to hopping of small polarons, because of the low value of the activation energy and the small negative activation volume. However, the solid-state physics approach can provide more arguments, for or against conduction by polarons. We have tried to bridge the gap between the two approaches and identify the physical quantities entering the phenomenological activation parameters. In particular, we have investigated the pressure dependence of the activation energy, and the physical meaning of the activation volume. Hopping is controlled by the binding energy of the polaron and by the value of the exchange integral, which increases with pressure causing the observed decrease of the activation energy. From the physical theory and the results of experiments at pressures up to 40 GPa and temperatures up to 400 ∘C, we have estimated the values of parameters characteristic of polarons: radius, mobility, time between jumps and adiabaticity. These values are compatible with conduction by small adiabatic polarons. The consequences for extrapolations to lower mantle conditions of the presence of a temperature dependent preexponential term in the expression for conductivity have been examined. It was found that the extrapolations are not significantly different from those using the Arrhenius equation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002690050243
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