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  • 1
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Neuroleptics ; Pharmacokinetics ; Long-acting neuroleptics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors review the literature regarding the pharmacokinetics of long-acting injectable neuroleptic drugs (LINS). There are important differences between LINS and oral neurolepties that affect their pharmacokinetics. By avoiding first pass metabolism in gut and liver, LINS result in lower circulating concentrations of metabolites than are found after oral administration. In addition, LINS take more time to reach a stable steady state than their oral counterparts. The clinical significance of these pharmacokinetic properties is discussed. The authors recommend that when patients are being changed from oral neuroleptics to LINS, that this conversion be done gradually over several months.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Neuroleptic ; Fluphenazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma fluphenazine concentrations (FLU) were measured in 45 patients with schizophrenic disorders who participated in a double-blind comparison of 5 and 25 mg fluphenazine decanoate (FD). The rise in plasma level of FLU 24 h after a “test dose” was significantly correlated with steady state FLU concentration at 12 weeks (for 5 mg patients, r=0.45, P=0.04; for 25 mg, r=0.78, P=0.005). Patients who had low FLU at baseline required nearly 6 months to reach a steady state when they received 25 mg. Patients who received 5 mg and had low FLU at baseline continued to demonstrate relatively low plasma levels for the entire 1st year. Although the mean FLU at 6 months was lower for patients who relapsed during the subsequent 18 months (0.57 ng/ml for relapsers vs 1.01 ng/ml for nonrelapsers), this difference was not statistically significant. When plasma levels from both dosage groups were combined, FLU at 12 weeks correlated significantly with factor scores for akinesia (r=0.52, P=0.002) and BPRS cluster scores for retardation (r=0.52, P=0.002). These results indicate that the measurement of fluphenazine plasma levels may be useful in determining when patients treated with FD are receiving drug doses which are likely to cause discomforting side effects.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Fluphenazine decanoate ; Metabolic sulfoxidation ; Fluphenazine sulfoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Highly sensitive radioimmunoassays were applied to study the sulfoxidation of fluphenazine in 30 schizophrenic patients maintained on either 5 mg or 25 mg fluphenazine decanoate by intramuscular injection every 14 days over a period of 6 months. The presence of the sulfoxide metabolite was detected in all but one of the patients, such that 97% of the 340 plasma samples analysed contained the metabolite. Interpatient variations in plasma levels of fluphenazine, fluphenazine sulfoxide, and in drug to metabolite plasma level ratios were several fold higher than the corresponding intrapatient variations at both dosages. There were statistically significant tendencies for mean plasma fluphenazine levels to rise and mean plasma sulfoxide levels to fall over the 6-month period of study among patients on the high dose, consistent with our previously reported observation that it takes 3–6 months to establish a steady state of fluphenazine with this dosage regimen. By contrast, there were no statistically significant changes in mean plasma levels of either fluphenazine or its sulfoxide in patients on the low dose. Nevertheless, there was a significant rise in fluphenazine to fluphenazine sulfoxide mean plasma level ratios in both dosage groups. It is difficult to assess the significance of the changes in the drug to metabolite ratios with time, since there are no kinetic data on the phase II metabolism (conjugation) of fluphenazine or fluphenazine sulfoxide. This study shows that sulfoxidation is an important major pathway in the metabolism of intramuscularly-administered fluphenazine, and implies that metabolic sites other than gut wall are also involved in the process.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1617-4623
    Keywords: NAD metabolism ; Regulation ; nadR ; Salmonella typhimurium ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The nadR locus (99 min) controls the transcription of several genes involved with either the biosynthesis (nadAB) or recycling (pncB) of NAD in Salmonella typhimurium. Point mutations in this locus were found to cause defects either in the transport of nicotinamide mononucleotide (PnuA-), the regulation of nadAB (NadR-) or both transport and regulation (PnuA-NadR-). Deletions or insertions into nadR always resulted in the PnuA- NadR- phenotypes. Merodiploids constructed with various combiminations of PnuA-, NadR- or PnuA-NadR- strains indicate a single complementation group. The results suggest the NadR product is a bifunctional regulatory protein. Operon fusions to lacZ (nadR:: Mud1-8) were used to show that nadR is not autoregulated and is transcribed in a clockwise direction. The gene was also cloned and located within a 2 kb EcoR1-BglII fragment.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 205 (1986), S. 507-514 
    ISSN: 1617-4623
    Keywords: Pyridine nucleotide cycle ; NAD metabolism ; Salmonella typhimurium ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A series of Mud1 and Tn10 insertions were identified in the pncA chromosome region of Salmonella typhimurium which is responsible for the production of nicotinamide deamidase. Both pncA (resulting in no nicotinamide deamidase activity) and pncX (resulting in lowered nicotinamide deamidase activity) insertions were constructed. In addition, mutants which could utilize nicotinamide as a sole source of nitrogen were isolated. These mutants, designated pncH, hyperproduce nicotinamide deamidase. Genetic studies utilizing pncX-lacZ and pncA-lacZ operon fusions indicate that pncX::Tn10 insertions reduce transcription of pncA-lac while pncH mutations increase the expression of both pncA-lacZ and pncX-lacZ. The gene order was determined as purB-pncA-pncX-gdh with transcription of both pncA and pncX occurring in the counterclockwise direction. Merodiploid studies suggest a model whereby pncX and pncA form an operon with the major promoter occurring upstream from pncX. A second, weaker promoter for pncA must be situated between pncX and pncA. The pncH mutations appear to occur in the pncX promoter (pncXp) increasing promoter activity.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 25 (1986), S. 1875-1893 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The heat denaturation of pepsinized bovine nonfibrillar and fibrillar collagen was studied by differential scanning calorimetry. For fibrillar preparations that had been rapidly precipitated with stirring at low ionic strength, then resuspended at physiological ionic strength, multiple denaturational transitions were observed. At heating rates of 10°C/min, melting endotherms occurred at about 44, 50, 53, and 57°C. Fibrillar collagen that was slowly gelled without stirring at physiological ionic strength exhibited a similar series of endotherms, but the lower melting transitions were less conspicuous. In contrast, nonfibrillar bovine collagen in acidic solution showed only a single denaturational transition at 40°C. Nonfibrillar solutions at pH 7, to which inhibitors of fibrillogenesis were added, showed a major endotherm as high as 46°C. These results suggest that reconstituted fibrillar collagen contains a heterogeneous fibril population, possibly including molecules in a nonfibrillar state. It was proposed that the multiple melting endotherms of such preparations were due to sequential melting of molecular and fibril classes, each with a distinct melting temperature. The fibrillar classes may represent three or more types of banded and nonbanded species that differ from each other in packing order, collagen concentration, and possibly also in fibril width and level of cross-linking.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 27 (1988), S. 1143-1157 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The effects of pH and temperature on the 300-MHz 1H-nmr spectra of three cardioactive polypeptides from sea anemones, anthopleurin-A from Anthopleura xanthogrammica (AP-A) and Anemonia sulcata toxins I and II (ATX I and II), are described. AP-A and ATX II exhibit major spectral heterogeneity. Evidence from the pH and temperature studies and from high performance liquid chromatography indicates that this heterogeneity is conformational rather than chemical in origin. By contrast, purified isotoxins of ATX I show no evidence of conformational heterogeneity. The pKa values of most of the ionizable groups in these polypeptides are not strongly perturbed by interactions in the tertiary structure, with the exception of one of the Asp carboxylates, which has a pKa of ≲ 2 in AP-A and ATX II and 3.0 in ATX I. Protonation of this carboxylate, suggested to be Asp-9, leads to a conformational change in all three molecules. All three polypeptides are thermally stable, showing some conformational changes but not major unfolding at elevated temperatures.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 121 (1988), S. 417-420 
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Synthese und Struktur von Cp3U=CHPMe3: Eine Verbindung mit U=C-MehrfachbindungGrünes, kristallines Cp3U=CHPMe3 wurde durch Umsetzung von Cp3UCl mit Li[CH2]2PMe2 oder H2C=PMe3 dargestellt. Seine Kristallstruktur wurde durch Röntgenbeugungsanalyse an Einkristallen bestimmt. Der kurze U=CH-Abstand von 2.274(8) Å und der große Winkel U—C—P von 143.5(5)° deuten Uran-Kohlenstoff-Mehrfachbindungscharakter an. Die 1J (13C1H)-Kopplungskonstanten in den CH-Gruppen zwischen Uran und Phosphor von Cp3U=CHPMe3 (95 Hz), Cp3U=CHPMe2Ph (100 Hz) und Cp3U=CHPPh2Me (113 Hz) sind auffallend klein. Den Strukturdaten kann aber keine agostische UCHP-Wechselwirkung entnommen werden.
    Notes: Green, crystalline Cp3U=CHPMe3 has been synthesized by the reaction of Cp3UCl with Li[CH2]2PMe2 or CH2=PMe3. Its crystal structure has been determined by single crystal X-ray diffraction. The short U=CH bond distance, 2.274(8) Å, and large U—C—P angle, 143.5(5)°, indicate uranium-carbon multiple bond character. The 1J(13C1H) coupling constants within the CH group between uranium and phosphorus in Cp3U=CHPPh2Me (95 Hz), Cp3U=CHPMe2Ph (100 Hz), and Cp3U=CHPPh2Me (113 Hz) are surprisingly small, but no agostic interaction UCHP can be derived from the structural data.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 29 (1989), S. 339-346 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The parallel-plate test fixture on a Rheometrics viscometer was electrically isolated so that the rheological and dielectric properties of a thermoset polymer system could be simultaneously measured. This enabled the relationship between the dielectric properties and the rheological properties to be directly examined. A close relationship was established between the dielectric properties (dipole relaxation time and specific conductivity) and the pre-gelation bulk viscosity. This relationship suggested that models similar in form to those used to describe the change in viscosity might be used to describe the changing dielectric properties. The limitations and advantages of two such models, which attempt to describe the time-temperature behavior of the dielectric properties, were then tested for use with a typical aerospace epoxy resin system.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 29 (1989), S. 1722-1729 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: A transient two-dimensional thermal model for resistance welding of thermoplastic composites is presented. A parametric study is conducted that yields insight into the welding process enabling some critical process and material parameters to be identified. Time to melt is predicted by the model and is successfully compared to experimental observations. Local heating and meltthrough can also be explained by the transient thermal model in agreement with experimental observations. Mode I fracture toughness of unidirectional graphite reinforced poly(etheretherketone) resistance welded double cantilever beam specimens are conducted under various process conditions. Experimental results indicate that under optimum process conditions, the interlaminar fracture toughness of the bulk compression-molded thermoplastic composite material can be achieved using resistance heating as a joining technique.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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