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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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: HER-2/neu ; c-erbB-2 ; chemotherapy ; tamoxifen ; drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amplification of the HER-2/neu (c-erbB-2) gene resulting in overexpression of the p185HER-2 growth factor receptor occurs in ~25% of early stage breast cancers. HER- 2/neu has been established as an important independent prognostic factor in early stage breast cancer in large cohorts of patients and in cohorts with very long (30 year) follow-up duration. New data are emerging to suggest that HER-2/neu may be useful not only as a prognostic factor but also as a predictive marker for projecting response to chemotherapeutics, antiestrogens, and therapeutic anti-HER- 2/neu monoclonal antibodies. In this review we highlight recent data on HER-2/neu as a predictive marker of response to breast cancer therapy and discuss the clinical implications of this information. The difficulty in comparing results from different data sets due to the wide variety of reagents and technologies used to detect HER-2/neu amplification/overexpression in clinical specimens is also discussed. Finally, we report results from experimental models of HER-2/neu overexpression which have been used in an effort to understand the relationship between HER- 2/neu and response to chemotherapeutics and antiestrogens in breast cancer.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Annals of software engineering 6 (1998), S. 131-144 
    ISSN: 1573-7489
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Software engineering is entering the educational mainstream at a time when budgets are tight, growth opportunities are limited, and existing disciplines are fighting to retain their share of a shrinking educational pie. This paper discusses some of the fundamental reasons why this situation is not likely to improve, and addresses ways software engineering can utilize modern computing and communication technology to overcome these limitations and, indeed, to lead the way in innovative education.
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  • 4
    ISSN: 1573-904X
    Keywords: drug delivery ; diabetes mellitus ; excipient ; insulin ; eye ; nose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Although DNA typing is an accurate, precise, and robust procedure, quality assurance is enhanced by availability of a suitable reference material. The National Institute of Standards and Technology (NIST) recently released a Standard Reference Material (SRM) that meets the calibration and quality assurance needs of laboratories that perform DNA typing. Each step of the analytical process of DNA typing may be verified by one or more of twenty different components of the SRM. As newer, more sensitive methods for DNA typing have been introduced into the human identification laboratory repertoire, new SRMs will be required for quality assurance. A second SRM for PCR-based tests is under development and soon to be available, is also described.
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  • 6
    ISSN: 1615-5947
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The utility of transserosal photoplethysmographic pulse oximetry (PO) to assess intestinal viability intraoperatively was evaluated using an experimental canine model. Comparisons of PO were made with continuous-wave Doppler ultrasound (CWDU) and fluorescein (FL) using histopathologic examination for control. Clinical examination estimates were included for reference. Four 20 cm portions of small bowel from each of four dogs were made ischemic by mesenteric ligation. Thus 320 individual 1 cm bowel segments were studied by means of PO, CWDU, FL, and control histologic grading for ischemia. Statistical analysis revealed no significant differences, with PO matching CWDU and FL in intraoperative assessment of small bowel viability. PO, which is readily available in most operating rooms, is a simpler method than CWDU or FL for assessing intestinal viability. This technique is operator independent, easy to interpret and repeat, and is well tolerated. PO is the preferred alternative for objective intraoperative assessment of intestinal viability.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 180 (1998), S. 33-41 
    ISSN: 1573-4919
    Keywords: mitochondrial metabolism ; long chain fatty acids ; acyl carnitine derivitives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The results of clinical and animal studies suggest that a short term period of moderate secondary carnitine deficiency, in and of itself, does not have a major effect on the cardiac contractile function, although substrate oxidation may be altered. However, with longer durations of carnitine deficiency, alterations occur within the heart that may result in impaired contractile performance, particularly at high workloads. At this point, the mechanisms responsible for the cardiac depression are uncertain. We hypothesize that the alterations in substrate metabolism produced by the carnitine deficient state results in inadequate ATP production under high workload conditions which result in impaired cardiac contractile performance. Carnitine deficiency may also induce a number of changes in gene expression of key enzymes required for normal cardiac contractile function and metabolism.
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  • 8
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Citrullinaemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthase. The deficiency of this enzyme results in an interruption in the urea cycle and the inability to dispose of excess ammonia derived from the metabolism of protein. The only treatment for this disorder has been dietary restriction of protein and supplementation with medications allowing for alternative excretion of excess nitrogen. Gene therapy offers the possibility of a long-term cure for disorders like citrullinaemia by expressing the deficient gene in the target organ. We have explored the use of adenoviral vectors as a treatment modality for citrullinaemia in two animal models, a naturally occurring bovine model and a murine model created by molecular mutagenesis. Mice treated with adenoviral vectors expressing argininosuccinate synthase lived significantly longer than untreated animals (11 days vs 1 day); however, the animals did not exhibit normal weight gain during the experiment, indicating that the therapeutic effectiveness of the transducing virus was suboptimal. It is speculated that part of the failure to observe better clinical outcome might be due to the deficiency of arginine. In the bovine model, the use of adenoviral vectors did not result in any change in the clinical condition of the animals or in the level of plasma ammonia. However, the use of 15N isotopic ammonia allowed us to assess the flux of nitrogen through the urea cycle during the experiment. These studies revealed a significant increase in the flux through the urea cycle following administration of adenoviral vectors expressing argininosuccinate synthase. We conclude that the use of adenoviral vectors in the treatment of citrullinaemia is a viable approach to therapy but that it will be necessary to increase the level of transduction and to increase the level of enzyme produced from the recombinant viral vector. Future experiments will be designed to address these issues.
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  • 9
    ISSN: 1573-2592
    Keywords: HIV-1 Immunogen ; antivirals ; viral load ; CD4 ; delayed-type hypersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.
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  • 10
    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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