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  • 1
    ISSN: 1573-904X
    Keywords: dissolution ; tablet stability ; solid state reaction ; croscarmellose sodium ; disintegrant ; infrared spectroscopy ; CP/MAS NMR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the cause for decrease in delavirdine mesylate 200 mg tablet dissolution upon exposure to high humidity. Methods. Dissolution testing was performed using the USP 2 (paddle) apparatus. Water in tablets was measured by Karl Fischer titration. 13C CP/MAS NMR was used to identify and quantify delavirdine form changes in tablets. FT-IR spectroscopy was used to monitor delavirdine form change in tablets and component mixes, and to investigate a solid state reaction with the disintegrant. Results. Dissolution extent of delavirdine mesylate 200 mg tablets was substantially decreased after exposure to high humidity. This effect is related to the amount of water present in the tablet matrix. 13C CP/ MAS NMR detected about 30% conversion from the mesylate salt of delavirdine to its free base form in the tablet matrix. FT-IR spectroscopy demonstrated that a solid state reaction occurs between the freed methanesulfonic acid and the carboxyl sites on the croscarmellose sodium disintegrant. Conclusions. Water is thought to act as both a reaction medium and a plasticizer for croscarmellose sodium, facilitating protonation of the carboxyl sites on the disintegrant. This reaction has the potential to occur for any acid salt of a free base. The limiting solubility of delavirdine free base formed in the tablets accounts for much of the decrease in the extent of dissolution. A change in inter-particle bonding can explain the reduction in tablet deaggregation during dissolution.
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  • 2
    ISSN: 1573-4919
    Keywords: streptozotocin ; blood vessels ; glycolysis ; glucose oxidation ; palmitate oxidation ; insulin-deficient diabetes ; sodium-potassium ATPase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several investigators have reported that carbohydrate metabolism is suppressed in blood vessels from diabetic (Db) rats. However, it is not known if metabolites from the reciprocal increase in oxidation of long-chain fatty acids that accompanies insulin-deficiency exacerbates the suppression of this pathway in the Db blood vessels. Such inhibition may have particularly deleterious consequences in vascular smooth muscle since aerobic glycolysis is believed to preferentially fuel the sarcolemmal Na/K ATPase in this tissue. Therefore, this study evaluated the effect of physiological (0.4 mM) and elevated (1.2 mM) concentrations of the long-chain fatty acid palmitate on both carbohydrate utilization and Na/K-ATPase activity in aorta from insulin-deficient Db rat. Thoracic aorta were removed from 10 week Db (streptozotocin 60 mg/Kg , i.v.) or control (C) rats and intima-media aortic preparations were incubated in the absence or presence of palmitate. Glycolysis (μM/g dry wt/h) and glucose oxidation (μM/g dry wt/h) were quantified using 3H-glucose and 14C-glucose, respectively. Na/K-ATPase activity was estimated by the measurement of 86rubidium uptake in the absence and presence of 2 mM ouabain. In the absence of exogenous palmitate, glycolysis (p 〈 0.05), glucose oxidation (p 〈 0.01) and the estimated ATP production from exogenous glucose were decreased in aorta from Db rat. However, despite this diminished rate of glycolysis, Na/K ATPase activity was similar in Db and C aorta. Palmitate (0.4 mM) inhibited Na/K ATPase activity and glucose oxidation to a similar extent in both Db and C but had no effect on glycolysis in either group. Elevation of palmitate to 1.2 mM had no additional inhibitory effect on glucose oxidation, Na/K ATPase activity or glycolysis in either the Db or C aorta. The metabolism of exogenous palmitate restored the ATP production in Db to control values. These data demonstrate that, despite the diminished glycolysis and glucose oxidation demonstrated in the Db tissue, Na/K ATPase activity was comparable in the C and Db aorta, in the absence or presence of exogenous long-chain fatty acid. Therefore, the accelerated oxidation of palmitate in diabetic vascular smooth muscle had no additional inhibitory effect on glycolysis or Na/K ATPase activity. These data suggest that Na/K ATPase activity in vascular smooth muscle is not impaired by the altered pattern of substrate utilization that occurs in insulin-deficient Db rats.
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  • 3
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: The electronic spectrum of germylidene (H2C(Double Bond)Ge), the simplest unsaturated germylene, has been observed for the first time. Jet-cooled H2CGe and D2CGe were produced by an electric discharge through tetramethylgermane diluted in argon at the exit of a supersonic expansion. High-resolution spectra of H2C74Ge and D2C74Ge, obtained from (CH3)4〈sup ARRANGE="STAGGER"〉74Ge prepared from isotopically enriched 74Ge metal, have been rotationally analyzed to yield the following r0 structures: r0″(CGe)=1.7908(2) Å, r0″(CH)=1.1022(5) Å, θ0″(HCH)=115.05(5)°, r0′(CGe)=1.914(4) Å, r0′(CH)=1.082(9) Å, and θ0′(HCH)=139.3(11)°. The 367–354 nm B˜1B2–X˜ 1A1 band system consists of prominent perpendicular bands involving the CGe stretching (ν3) and CH2 scissors (ν2) vibrations and a weaker series of vibronically induced parallel bands involving the CH2 rocking mode (ν6). Vibronic bands involving Δv=2 changes in ν6(b2) and ν4(b1) have also been assigned. The fluorescence decays of single rotational levels of the 000 band of H2C74Ge exhibit molecular quantum beats for about 70% of the levels surveyed. Density of states arguments reveal that most of the beats originate from interactions with high rovibronic levels of the ground state. In one case, hyperfine splittings in the Fourier transform of the beat pattern indicate an accidental coincidence with an excited triplet state level. The less frequent occurrence of quantum beats in germylidene compared to silylidene, where they are almost universal, can be attributed to the smaller density of ground state levels at the zero-point energy of the S2 state in the former. © 1999 American Institute of Physics.
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  • 4
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
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  • 5
    ISSN: 1572-901X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of the replacement of dmso in FePc(dmso)2 by piperidine and 11 substituted pyridines, to form FePc(base)2 species, have been studied by stopped-flow techniques. For the first step a linear free energy relationship (LFER) exists between the rate constant for fission of base from FePc(base)(dmso) and the gas phase proton affinity of the base, from bases with low proton affinity (CO) to high proton affinity (CN−). The rate constant for dmso fission from FePc(dmso)2 was estimated to be ca. 420,000 s−1, and this fission process largely governs the rate of the first step for neutral bases. The slow first step for the reaction with cyanide ion as base can be explained when the energy needed to de-pair cyanide and potassium ions is taken into account. In the second step the formation rate constants of FePc(base)2 species cover one order of magnitude for neutral bases, and the base dissociation rate constants cover two orders of magnitude, with a good LFER between these constants and the pKBH of the leaving group. There is also a good LFER between the equilibrium constant for bis-base complex formation and these same dissociation rate constants.
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  • 6
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Sir A trial is under way in San Francisco, California, involving a patent dispute between Genentech, Inc. and the University of California at San Francisco (see page 289 of this issue and ref. 1). During this trial, Peter Seeburg of the Max Planck Institute ...
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 399.1999, Supplementary, A23-, (9 S.) 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Studies of the molecular basis of Alzheimer's disease exemplify the increasingly blurred distinction between basic and applied biomedical research.The four genes so far implicated in familial Alzheimer's disease have each been shown to elevate brain levels of the self-aggregating amyloid-β ...
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  • 8
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Accumulation of the amyloid-β protein (Aβ) in the cerebral cortex is an early and invariant event in the pathogenesis of Alzheimer's disease. The final step in the generation of Aβ from the β-amyloid precursor protein is an apparently intramembranous proteolysis by the ...
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  • 9
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
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  • 10
    ISSN: 1435-1528
    Keywords: Key words Liquid crystal ; Conoscopy ; Flow-aligning ; Tumbling ; Mixtures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Abstract  The results of an experimental study to measure the tumbling parameter, λ, for various small-molecule liquid crystals and their mixtures are presented. The methods used include textural observations (twist walls), a direct method, a rheological method, and the oscillatory method developed by Mather, Pearson, and Burghardt in 1995. The single-component results are compared with a molecular theory derived in 1995 by Archer and Larson as well as Kröger and Sellers, which predicts the temperature dependence of λ, while the results from the binary mixtures are compared to a continuum theory derived by Rey in 1996, giving the concentration dependence of λ. The results from the four experimental methods agree with each other for single-component liquid crystals, but not for mixtures. This suggests a failure of the single director Leslie-Ericksen theory to describe the rheology of liquid crystal mixtures.
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