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971.
Drug safety has become a very important subject, and more countries have joined in the fight against counterfeit drugs. This study demonstrated a non-invasive Raman spectroscopy method that could be utilized for screening liquid injectable drugs for spurious/falsely-labeled/falsified/counterfeit medical products (SFFCs). Two problems were solved to remove the blocks in identification and quantitation: one problem was the weak API signal extraction from the non-invasive Raman spectra and the other was the problem of Raman absolute measurement. Principal component analysis (PCA) and classical least square (CLS) algorithms were performed to establish the models. Water was chosen as the “internal standard” to normalize the spectra to solve the problem of Raman absolute measurement. The results showed that the 11 positive samples and 66 negative samples were all well identified with a threshold of 0.95. One of the positive samples contained the excipient propylene glycol, which was identified successfully at the same time. The accuracy of quantitative results was approximately 5% for doxofylline liquid injectables and about 10% for the low-concentration and big glass bottle-containers of Levofloxacin Lactate and Sodium Chloride Injections as compared to the results using an HPLC method, this is satisfactory for fast screening of SFFCs. In conclusion, with the development of a database of identification and quantitation models, this method may determine liquid injectable drugs in a fast and non-invasive way and become one of the most powerful weapons against SFFCs.
Graphical Abstract
Open in a separate windowᅟElectronic supplementary material
The online version of this article (doi:10.1208/s12249-015-0286-0) contains supplementary material, which is available to authorized users.KEY WORDS: CLS, liquid injectables, non-invasive Raman fast screening method, PCA, SFFCs (Spurious/falsely-labeled/falsified/counterfeit medical products) 相似文献972.
Lan Wu Yanli Qiao Lina Wang Jiahua Guo Guocheng Wang Wei He Lifang Yin Jinhua Zhao 《AAPS PharmSciTech》2015,16(5):1051-1058
AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was −2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the Cmax of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.KEY WORDS: bioavailability, HPLC-MS/MS, self-microemulsifying drug delivery system, solubilization, stability 相似文献
973.
974.
DNA lesions caused by UV radiation are highly recombinogenic. In wild-type cells, the recombinogenic effect of UV partially reflects the processing of UV-induced pyrimidine dimers into DNA gaps or breaks by the enzymes of the nucleotide excision repair (NER) pathway. In this study, we show that unprocessed pyrimidine dimers also potently induce recombination between homologs. In NER-deficient rad14 diploid strains, we demonstrate that unexcised pyrimidine dimers stimulate crossovers, noncrossovers, and break-induced replication events. The same dose of UV is about six-fold more recombinogenic in a repair-deficient strain than in a repair-proficient strain. We also examined the roles of several genes involved in the processing of UV-induced damage in NER-deficient cells. We found that the resolvase Mus81p is required for most of the UV-induced inter-homolog recombination events. This requirement likely reflects the Mus81p-associated cleavage of dimer-blocked replication forks. The error-free post-replication repair pathway mediated by Mms2p suppresses dimer-induced recombination between homologs, possibly by channeling replication-blocking lesions into recombination between sister chromatids. 相似文献
975.
Qiulian Zhou Lei Wei Chongjun Zhong Siyi Fu Yihua Bei Radu‐Ionuț Huică Fei Wang Junjie Xiao 《Journal of cellular and molecular medicine》2015,19(8):2036-2042
Telocytes (TCs) are a distinct type of interstitial cells, which are featured with a small cellular body and long and thin elongations called telopodes (Tps). TCs have been widely identified in lots of tissues and organs including heart. Double staining for CD34/PDGFR‐β (Platelet‐derived growth factor receptor β) or CD34/Vimentin is considered to be critical for TC phenotyping. It has recently been proposed that CD34/PDGFR‐α (Platelet‐derived growth factor receptor α) is actually a specific marker for TCs including cardiac TCs although the direct evidence is still lacking. Here, we showed that cardiac TCs were double positive for CD34/PDGFR‐α in primary culture. CD34/PDGFR‐α positive cells (putative cardiac TCs) also existed in mice ventricle and human cardiac valves including mitral valve, tricuspid valve and aortic valve. Over 87% of cells in a TC‐enriched culture of rat cardiac interstitial cells were positive for PDGFR‐α, while CD34/PDGFR‐α double positive cells accounted for 30.25% of the whole cell population. We show that cardiac TCs are double positive for CD34/PDGFR‐α. Better understanding of the immunocytochemical phenotypes of cardiac TCs might help using cardiac TCs as a novel source in cardiac repair. 相似文献
976.
Fei Liu Yingju Liu Rui‐Gang Xu Guifu Dai Liu‐Xi Zhao Yafeng Wang Hong‐Min Liu Feng‐Wu Liu Christophe Pannecouque Piet Herdewijn 《化学与生物多样性》2015,12(5):813-822
The synthesis of [(2′,5′‐dihydrofuran‐2‐yl)oxy]methyl‐phosphonate nucleosides with a 2‐substituted adenine base moiety starting from 2‐deoxy‐3,5‐bis‐O‐(4‐methylbenzoyl)‐α‐L ‐ribofuranosyl chloride and 2,6‐dichloropurine is described. The key step is the regiospecific and stereoselective introduction of a phosphonate synthon at C(2) of the furan ring. None of the synthesized compounds showed significant in vitro activity against HIV, BVDV, and HBV. 相似文献
977.
978.
Li Fei SiSi Tian Ruth Moysey Mihaela Misca John J. Barker Myron A. Smith Paul A. McEwan Ewa S. Pilka Lauren Crawley Tom Evans Dapeng Sun 《PloS one》2015,10(2)
A novel exonuclease, designated as MszExo I, was cloned from Methylocaldum szegediense, a moderately thermophilic methanotroph. It specifically digests single-stranded DNA in the 3ʹ to 5ʹ direction. The protein is composed of 479 amino acids, and it shares 47% sequence identity with E. coli Exo I. The crystal structure of MszExo I was determined to a resolution of 2.2 Å and it aligns well with that of E. coli Exo I. Comparative studies revealed that MszExo I and E. coli Exo I have similar metal ion binding affinity and similar activity at mesophilic temperatures (25–47°C). However, the optimum working temperature of MszExo I is 10°C higher, and the melting temperature is more than 4°C higher as evaluated by both thermal inactivation assays and DSC measurements. More importantly, two thermal transitions during unfolding of MszExo I were monitored by DSC while only one transition was found in E. coli Exo I. Further analyses showed that magnesium ions not only confer structural stability, but also affect the unfolding of MszExo I. MszExo I is the first reported enzyme in the DNA repair systems of moderately thermophilic bacteria, which are predicted to have more efficient DNA repair systems than mesophilic ones. 相似文献
979.
Zhiyong Yang Yushun Zhang Liming Dong Chong Yang Shanmiao Gou Tao Yin Heshui Wu Chunyou Wang 《PloS one》2015,10(5)
ObjectiveFew data are available on the potential role of inflammatory mediators and T lymphocytes in persistent organ failure (POF) in acute pancreatitis (AP). We conducted a retrospective study to characterize their role in the progression of POF in AP.MethodsA total of 69 AP patients presented within 24 hours from symptom onset developing organ failure (OF) on admission were included in our study. There were 39 patients suffering from POF and 30 from transient OF (TOF). On the 1st, 3rd and 7th days after admission, blood samples were collected for biochemical concentration monitoring including serum IL-1β, IL-6, TNF-α and high-sensitivity C-reactive protein (hs-CRP). The proportions of peripheral CD4+ and CD8+ T lymphocytes were assessed based on flow cytometry simultaneously.ResultsPatients with POF showed a significantly higher value of IL-1β and hs-CRP on day 7 compared with the group of TOF (P < 0.05). Proportions of CD4+ T cells on days 1, 3, 7 and CD4+ / CD8+ ratio on day 1 were statistically lower in the group of POF patients (P < 0.05). A CD4+ T cell proportion of 30.34% on day 1 predicted POF with an area under the curve (AUC) of 0.798, a sensitivity with 61.54% and specificity with 90.00%, respectively.ConclusionsThe reduction of peripheral blood CD4+ T lymphocytes is associated with POF in AP, and may act as a potential predictor. 相似文献
980.
Fei Wang Shu Li Xin-Wen Bai Xiao-Peng Ren Li-Lin Rao Jin-Zhen Li Huan Liu Hong-Zhi Liu Bin Wu Rui Zheng 《PloS one》2015,10(5)
Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the “town dislocation effect.” When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention. 相似文献