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A sensitive and stereoselective high-performance liquid chromatographic assay for the quantitative determination of the analgesic tramadol and O-demethyltramadol, an active metabolite, is described in this work. Ketamine was used as internal standard. The assay involved a single tert-butymethylether extraction and liquid chromatography analysis with fluorescence detection. Chromatography was performed at 20 degrees C on a Chiracel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate) as stationary phase, preceded by an achiral end-capped C18 column. The mobile phase was a mixture of phosphate buffer (containing sodium perchlorate (0.2 M) and triethylamine (0.09 M) adjusted to pH 6) and acetonitrile (80:20). The method developed was validated. The limit of quantitation of each enantiomer of tramadol and its active metabolite by this method was 0.5 ng/mL; only 0.5 mL of the plasma sample was required for the determination. The calibration curve was linear from 0.5 to 750 ng/mL for tramadol enantiomers, and from 0.5 to 500 ng/mL for O-demethyltramadol enantiomers. Intra and interday precision [coefficient of variation (CV)] did not exceed 10%. Mean recoveries of 95.95 and 97.87% for (+)R,R- and (-)S,S-tramadol and 97.70 and 98.79% for (+)R,R- and (-)S,S-O-demethyltramadol with CVs < 2.15% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 100 mg of tramadol by the intravenous route. 相似文献
2.
Seventy-six Brahman cows and first-calf heifers were assigned to one of two groups: 1) normal suckling (34 cows) or 2) twice-daily suckling (45 minutes of suckling each time; 42 cows). Twice-daily suckling was carried out from 30 days postcalving until weaning (seven months). All animals were maintained under artificial insemination for a four-month breeding period. Mean pregnancy rate was 63.06 +/- 0.06% and was influenced by suckling group (P<0.01) and number of parturitions (P<0.05). The pregnancy rates were 33% higher in twice-daily suckled cows. Forty-four percent of the first calf heifers in the twice-daily suckling group became pregnant compared to 9% in the normal suckling group (P<0.01). Twice-daily suckling improved pregnancy rate without depressing preweaning calf performance. 相似文献
3.
Randi T Garmo Steinar Waage Ståle Sviland Britt IF Henriksen Olav Østerås Olav Reksen 《Acta veterinaria Scandinavica》2010,52(1):11
Background
The objectives of this study were to investigate whether there were differences between Norwegian Red cows in conventional and organic farming with respect to reproductive performance, udder health, and antibiotic resistance in udder pathogens. 相似文献4.
ZP Parra-Guillen J Fioravanti J Medina-Echeverz C Gomar N Ardaiz IF Troconiz P Berraondo 《PloS one》2012,7(7):e42100
Interferon alpha linked to apolipoprotein A-I has been recently proposed as an improved interferon-based therapy. In the present study, we aimed to develop a computational model to gain further insight into the in vivo behaviour of this new fusion protein. In order to facilitate in vivo evaluation of interferon and the fusion protein without altering their biological properties, green fluorescent protein was incorporated into their structures. Kinetic and dynamic behaviour of both compounds was successfully described after plasmid hydrodynamic administration and in situ synthesis of the studied proteins. Results from the modelling exercise showed that apolipoprotein A-I conferred a modified kinetic behaviour, varying molecule distribution and prolonging half-life without altering liver dynamic performance. However, differences in the gene expression activity were observed at brain level between both compounds. Those differences could be explained by modifications in the dynamic, but also in the biodistribution properties, which would be worth evaluating in future experiments. Therefore, the modelling approach provided a global comprehension of a complex system and allowed us to compare the in vivo behaviour of both compounds and to identify critical aspects that might be important to understand the system better and suggests a need for new model-based experiments. 相似文献
5.
Pramod Kumar Yadav Gurmit Singh Satendra Singh Budhayash Gautam Esmaiel IF Saad 《Bioinformation》2012,8(14):664-672
The emergence of multidrug-resistant strain of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strain
has highlighted the urgent need for the alternative and effective therapeutic approach to combat the menace of this nosocomial
pathogen. In the present work novel potential therapeutic drug targets have been identified through the metabolic pathways
analysis. All the gene products involved in different metabolic pathways of CA-MRSA in KEGG database were searched against
the proteome of Homo sapiens using the BLASTp program and the threshold of E-value was set to as 0.001. After database
searching, 152 putative targets were identified. Among all 152 putative targets, 39 genes encoding for putative targets were
identified as the essential genes from the DEG database which are indispensable for the survival of CA-MRSA. After extensive
literature review, 7 targets were identified as potential therapeutic drug target. These targets are Fructose-bisphosphate aldolase,
Phosphoglyceromutase, Purine nucleoside phosphorylase, Uridylate kinase, Tryptophan synthase subunit beta, Acetate kinase and
UDP-N-acetylglucosamine 1-carboxyvinyltransferase. Except Uridylate kinase all the identified targets were involved in more than
one metabolic pathways of CA-MRSA which underlines the importance of drug targets. These potential therapeutic drug targets
can be exploited for the discovery of novel inhibitors for CA-MRSA using the structure based drug design (SBDD) strategy. 相似文献
6.
In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the
most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub
family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in
better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to
understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to
BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly
showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to
different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server
which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new
ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics. 相似文献
7.
Background
Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks.Methods
We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls.Results
Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients.Conclusions
These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy. 相似文献8.
9.
Semiparametric models for antagonistic drug interactions 总被引:1,自引:0,他引:1
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