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Nkx2-5 activity is essential for cardiomyogenesis 总被引:14,自引:0,他引:14
Jamali M Rogerson PJ Wilton S Skerjanc IS 《The Journal of biological chemistry》2001,276(45):42252-42258
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Therapeutic relevance of altered cytokine expression 总被引:6,自引:0,他引:6
Cytokines and their receptors have numerous physiological functions. Altered concentrations of these mediators are associated with various afflictions. For example, over-expression of cytokines has been associated with altered drug concentrations and activity. Greater concentrations of cardiovascular drugs have been observed in humans and laboratory animals with various types of inflammatory disorders compared to healthy controls. Interestingly, the observed higher concentrations of drugs such as propranolol and verapamil have not been associated with increased effects. Indeed, reduced response to these cardiovascular drugs is observed, suggestive of cytokine-mediated downregulation of receptors. Increased cytokine concentrations have also been associated with decreased response to drugs used in treatment of other disorders such as AIDS, asthma and psychiatric diseases. This reduced response to drug in the presence of altered cytokine concentrations is especially relevant to the elderly population which has a greater incidence of multiple diseases and elevated concentrations of various cytokines compared to younger individuals. Furthermore, inflammatory conditions and their accompanied increased over-expression of cytokines are suggested to be the main determinants of therapeutic failure in myocardial infarction and angina. Therefore, altered cytokine concentrations may influence therapeutic outcomes of pharmacotherapy and result in treatment failure. 相似文献
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Jamali B Andersen SG Brødholt H Wendel L Bødstrup V 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,810(2):251-257
A simple and sensitive method has been developed and validated for purity determination of FF-MAS (also known as (3beta,20R)-4,4-dimethylcholesta-8,14,24-trien-3-ol an endogenous substance usually present in the pre-ovulatory follicular fluid) at very low concentrations (200 ng per unit) in pharmaceutical formulations containing RECOMBUMIN (recombinant human albumin) as the matrix. The paper focuses on development of the sample preparation for the product containing recombinant human albumin. After removal of recombinant human albumin by precipitation using a mixture of water and ethanol, the FF-MAS was concentrated by evaporation using a vacuum centrifuge and the prepared sample was analyzed. The purity method was based on a reversed-phase high performance liquid chromatography (RP-HPLC) with ultraviolet absorption detection at 250 nm. The method was validated according to ICH guidelines. The method indicated a significant degree of specificity with good selectivity and no significant effect from the matrix. The limit of detection was found to be 0.3-0.8% (depending on the impurity) corresponding to 1.9-5.1 ng. The limit of quantification was found to be 0.8-2.5% (depending on the impurity) corresponding to 5.2-16 ng. The recovery was found to be between 90 and 101% for the FF-MAS, and 100-129% for the six known impurities. The tested range for FF-MAS was from 320 to 960 ng corresponding to 50-150% of the nominal concentration (640 ng, injection volume is 100 microl). The linearity of each compound (FF-MAS and the six impurities) was investigated. The squared correlation coefficient (r(2)) was 0.999 for FF-MAS (50-150% level) and 0.977-0.998 for the six known impurities (at four levels: 0.20, 0.50, 1.00, 2.00%). The R.S.D. in the repeatability study was found to be 9.2% for the total amount of impurities, and 10.4% for single impurities. The R.S.D. in the intermediate precision study was found to be 10.9% for total impurities, and 12.0% for single impurities. The validation results showed that the method was suitable for the purity analysis. The validated method was then ready for use for samples analysis of phase II clinical studies and the stability investigations of the pharmaceutical product. 相似文献
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Jamali F Sharifi-Tehrani A Okhovvat M Zakeri Z Saberi-Riseh R 《Communications in agricultural and applied biological sciences》2004,69(4):649-651
In this survey, Fusarium oxysporum was isolated from roots infected plants and was shown to be pathogenic. Experiment were carried out with seven antagonistic bacteria. Based on biochemical, Physiological and morphological tests, isolates B-120, B-32, B-28 and B-22 were identified as Bacillus subtilis and isolates Pf-100, Pf-10 and CHAO as Pseudomonas fluorescens. In greenhouse studies, only isolate B-120 (Less than benomyl) reduced Fusarium wilt of chickpea in both seed and soil treatments. The application of antagonistic bacteria had no different effects on plant growth factors. Soil treatment of bacteria had a better effects on plant growth than that of bacterial seed treatment. The use of antagonists (B-120, B-28, B-120 and CHAO) in combination had no significant effect on plant growth factors and reduction wilt disease than that each isolate was applied individually. 相似文献
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Silvia Alessi-Severini Ronald T. Coutts Fakhreddin Jamali Franco M. Pasutto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1992,582(1-2)
Methocarbamol enantiomers in rat and human plasma were quantified using a stereospecific high-performance liquid chromatographic method. Racemic methocarbamol and internal standard, (R)-(−)-flecainide, were isolated from plasma by a single-step extraction with ethyl acetate. After derivatization with the enantiomerically pure reagent (S)-(+)-1-(1-naphthyl)ethyl isocyanate, methocarbamol diastereomers and the (R)-flecainide derivative were separated on a normal-phase silica column with a mobile phase consisting of hexane—isopropanol (95:5, v/v) at a flow-rate of 1.6 ml/min. Ultraviolet detection was carried out at a wavelength of 280 nm. The resolution factor between the diastereomers was 2.1 (α = 1.24). An excellent linearity was observed between the methocarbamol diastereomers/internal standard derivative peak-area ratios and plasma concentrations, and the intra- and inter-day coefficients of variation were always <9.8%. The lowest quantifiable concentration was 0.5 μg/ml for each enantiomer (coefficients of variation of 9.8 and 8.8% for (S)- and (R)-methocarbamol, respectively), while the limit of detection (signal-to-noise ratio 3:1) was approximately 10 ng/ml. The assay was used to study the pharmacokinetics of methocarbamol enantiomers in a rat following intravenous administration of a 120 mg/kg dose of racemic methocarbamol and to evaluate plasma and urine concentrations in a human volunteer after oral administration of a 1000-mg dose of the racemate. The method is suitable for stereoselective pharmacokinetic studies in humans as well as in animal models. 相似文献
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Nasir Ullah Zhangjian Huang Forough Sanaee Alexandra Rodriguez-Dimitrescu Fahad Aldawsari Fakhreddin Jamali 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1018-1028
The carboxylic acid group (–COOH) present in classical NSAIDs is partly responsible for the gastric toxicity associated with the administration of these drugs. This concept has been extensively proven using NSAID prodrugs. However, the screening of NSAIDs with no carboxylic acid at all has been neglected. The goal of this work was to determine if new NSAID derivatives devoid of acidic moieties would retain the anti-inflammatory activity of the parent compound, without causing gastric toxicity. To test this concept, we replaced the carboxylic acid group in ibuprofen, flurbiprofen, and naproxen with three ammonium moieties. We tested the resulting water-soluble NSAID derivatives for anti-inflammatory and ulcerogenic activity in vitro and in vivo. In this regard, we observed that all non-acidic NSAIDs exerted a potent anti-inflammatory activity, suggesting that the acid group in commercial 2-phenylpropionic acid NSAIDs not be an essential requirement for anti-inflammatory activity. These data provide complementary evidence supporting the discontinuation of ulcerogenic acidic NSAIDs. 相似文献
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Asghar Abdoli Hoorieh Soleimanjahi Abbas Jamali Parvaneh Mehrbod Shima Gholami Zahra Kianmehr Neda Feizi Maryam Saleh Fariborz Bahrami Talat Mokhtari-Azad Mohsen Abdoli Masoumeh Tavassoti Kheiri 《Biotechnology letters》2016,38(6):941-948