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1

Yin, Jiayi, Fengcheng Li, Ying Zhou, Minjie Mou, Yinjing Lu, Kangli Chen, Jia Xue, et al. "INTEDE: interactome of drug-metabolizing enzymes." Nucleic Acids Research 49, no. D1 (October 12, 2020): D1233—D1243. http://dx.doi.org/10.1093/nar/gkaa755.

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Abstract Drug-metabolizing enzymes (DMEs) are critical determinant of drug safety and efficacy, and the interactome of DMEs has attracted extensive attention. There are 3 major interaction types in an interactome: microbiome–DME interaction (MICBIO), xenobiotics–DME interaction (XEOTIC) and host protein–DME interaction (HOSPPI). The interaction data of each type are essential for drug metabolism, and the collective consideration of multiple types has implication for the future practice of precision medicine. However, no database was designed to systematically provide the data of all types of DME interactions. Here, a database of the Interactome of Drug-Metabolizing Enzymes (INTEDE) was therefore constructed to offer these interaction data. First, 1047 unique DMEs (448 host and 599 microbial) were confirmed, for the first time, using their metabolizing drugs. Second, for these newly confirmed DMEs, all types of their interactions (3359 MICBIOs between 225 microbial species and 185 DMEs; 47 778 XEOTICs between 4150 xenobiotics and 501 DMEs; 7849 HOSPPIs between 565 human proteins and 566 DMEs) were comprehensively collected and then provided, which enabled the crosstalk analysis among multiple types. Because of the huge amount of accumulated data, the INTEDE made it possible to generalize key features for revealing disease etiology and optimizing clinical treatment. INTEDE is freely accessible at: https://idrblab.org/intede/
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Feng, Siqi, Anqi Li, Yi-Chao Zheng, and Hong-Min Liu. "Role of Drug-metabolizing Enzymes in Cancer and Cancer Therapy." Current Drug Metabolism 21, no. 1 (May 14, 2020): 67–76. http://dx.doi.org/10.2174/1389200221666200103111053.

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Background: Cancer is one of the most serious diseases threatening human health with high morbidity and mortality in the world. For the treatment of cancer, chemotherapy is one of the most widely used strategies, for almost all kinds of tumors and diverse stages of tumor development. The efficacy of chemotherapy not only depends on the activity of the drug administrated but also on whether the compound could reach the effective therapeutic concentration in tumor cells. Therefore, expression and activity of drug-metabolizing enzymes (DMEs) in tumor tissues and metabolic organs of cancer patients are important for the dispositional behavior of anticancer drugs as well as the clinical response of chemotherapy. Methods: This review summarizes the recent advancement of the DMEs expression and activity in various cancers, as well as the potential regulatory mechanisms of major DMEs in cancer and cancer therapy. Results: Compared to normal tissues, expression and activity of major DMEs are significantly dysregulated in patients by various factors including epigenetic modification, ligand-activated transcriptional regulation and signaling pathways. Additionally, DMEs play an important role in anticancer drug efficacy, chemoresistance as well as the activation of prodrugs. Conclusion: This review reinforces a more comprehensive understanding of DMEs in cancer and cancer therapy, and provides more opportunities for cancer therapy.
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Leal, Giselle Mirtes Amaral, Mafra Raiele Torres Oliveira, Vivianne Camila de Souza Bastos, Maria De Fátima Alcântara Barros, Antônio Geraldo Cidrão De Carvalho, Shirley Lima Campos, Marcelo Renato Guerino, Kátia Karina Do Monte-Silva, Angélica Da Silva Tenório, and Maria Das Graças Rodrigues De Araújo. "Study of musculoskeletal disorders in physical therapists: correlation with routine work." Manual Therapy, Posturology & Rehabilitation Journal 12 (September 8, 2014): 191. http://dx.doi.org/10.17784/mtprehabjournal.2014.12.191.

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Introduction: Work-Related Musculoskeletal Disorders (MSDs) affect health professionals by frequent exposure to physical and mental overloads during the workday. Physiotherapy aims to promote functional health of the individual, however ergonomic conditions in their workplace are often precarious and that along with the activities and repetitive movements resisted overload the musculoskeletal system inducing damage to your physical condition. Objective: Identify the occurrence of Musculoskeletal Disorders (DMEs) in physical therapists working in public and private health services in Recife-Pernambuco, recording determinants and establishing relationship with clinical practice and the workload of the tests. Method: Observational study of physiotherapists of both genders. Peres administered questionnaire collected personal information, professional performance and DMEs Results: 41 physiotherapists; 85.4% reported DMEs, females (80.5%); 41.4% between 24-30 years; places of work, hospitals (70.7%) and clinical (63.4%); predominance of lesions in the spine and upper limbs; 65.7% changed work habits due to the occurrence of DMEs. Significant correlation between age and gender prevalence in females; since the occurrence of DMEs was not significantly correlated with time of practice, with workload, with the number of daily visits nor to rest at work. Conclusion: The volunteers showed high percentage of involvement by DMEs, especially in the spine, which seems to be related to the age and gender of the therapist. The study indicates that physical therapists are an exposed to risk for developing occupational musculoskeletal disorders profession, requiring awareness of students and professionals about proper use of the body itself, the risks of the profession in order to prevent future physical limitations.
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Liu, Chunxiao, Hui Li, Jing Lin, Ying Wang, Xiaoyang Xu, Zong-Ming (Max) Cheng, and Yonghong Chang. "Genome-Wide Characterization of DNA Demethylase Genes and Their Association with Salt Response in Pyrus." Genes 9, no. 8 (August 6, 2018): 398. http://dx.doi.org/10.3390/genes9080398.

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DNA methylation plays important roles in genome protection and the regulation of gene expression and it is associated with plants’ responses to environments. DNA demethylases are very important proteins in DNA methylation regulation. In this study, we performed genome-wide and deep analysis of putative demethylases (DMEs) in pear. Seven DME genes were found in the pear genome and were defined as PbDME1–7 based on their domain organization. Results were supported by the gene structural characteristics and phylogenetic analysis. The gene structure of the DME genes were relatively complex and the DME7 proteins didn’t contain the Perm_CXXC domain. The DME genes experienced a whole genome duplication event (WGD) that occurred in the ancestor genome of pear and apple before their divergence based on the Ks values. Expression results showed that high salinity stress could influence the expression level of DMEs and salt-responsive genes in Pyrus betulaefolia. Furthermore, the methylation levels of salt-responsive genes changed under salt stress treatment. Results suggested important roles of PbDME genes in response to salt stress and are useful for better understanding the complex functions of this DME genes, which will facilitate epigenetic studies in pear trees salt tolerance.
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Li, Xiaoyan, Yiyan Lu, Xiaojun Ou, Sijing Zeng, Ying Wang, Xiaoxiao Qi, Lijun Zhu, and Zhongqiu Liu. "Changes and sex- and age-related differences in the expression of drug metabolizing enzymes in a KRAS-mutant mouse model of lung cancer." PeerJ 8 (November 18, 2020): e10182. http://dx.doi.org/10.7717/peerj.10182.

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Background This study aimed to systematically profile the alterations and sex- and age-related differences in the drug metabolizing enzymes (DMEs) in a KRAS-mutant mouse model of lung cancer (KRAS mice). Methodology In this study, the LC-MS/MS approach and a probe substrate method were used to detect the alterations in 21 isoforms of DMEs, as well as the enzymatic activities of five isoforms, respectively. Western blotting was applied to study the protein expression of four related receptors. Results The proteins contents of CYP2C29 and CYP3A11, were significantly downregulated in the livers of male KRAS mice at 26 weeks (3.7- and 4.4-fold, respectively, p < 0.05). SULT1A1 and SULT1D1 were upregulated by 1.8- to 7.0- fold at 20 (p = 0.015 and 0.017, respectively) and 26 weeks (p = 0.055 and 0.031, respectively). There were positive correlations between protein expression and enzyme activity for CYP2E1, UGT1A9, SULT1A1 and SULT1D1 (r2 ≥ 0.5, p < 0.001). Western blotting analysis revealed the downregulation of AHR, FXR and PPARα protein expression in male KRAS mice at 26 weeks. For sex-related differences, CYP2E1 was male-predominant and UGT1A2 was female-predominant in the kidney. UGT1A1 and UGT1A5 expression was female-predominant, whereas UGT2B1 exhibited male-predominant expression in liver tissue. For the tissue distribution of DMEs, 21 subtypes of DMEs were all expressed in liver tissue. In the intestine, the expression levels of CYP2C29, CYP27A1, UGT1A2, 1A5, 1A6a, 1A9, 2B1, 2B5 and 2B36 were under the limitation of quantification. The subtypes of CYP7A1, 1B1, 2E1 and UGT1A1, 2A3, 2B34 were detected in kidney tissue. Conclusions This study, for the first time, unveils the variations and sex- and age-related differences in DMEs in C57 BL/6 (WT) mice and KRAS mice.
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Qi, Shixiong, Xiuli Wang, Xue Li, Tao Qian, and Qiwen Zhang. "Enhancing Integrated Energy Distribution System Resilience through a Hierarchical Management Strategy in District Multi-Energy Systems." Sustainability 11, no. 15 (July 26, 2019): 4048. http://dx.doi.org/10.3390/su11154048.

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The requirement for energy sustainability drives the development of integrated energy distribution systems (IEDSs). In this paper, considering the coordination of district multi-energy systems (DMESs), a hierarchical management strategy is proposed to enhance IEDS resilience. The proposed strategy is divided into three modes: the normal operation mode, the preventive operation mode and the resilient operation mode. In the normal operation mode, the objective of DEMSs is to minimize the operation costs. In the preventive operation mode, the objective of DEMSs is to maximize the stored energy for mitigating outage. The resilient operation mode consists of two stages. DMESs schedule their available resources and broadcast excess generation capacities or unserved loads to neighboring DMESs through the cyber communication network in the first stage. In the second stage, DMESs interchange electricity and natural gas with each other through the physical common bus for global optimization. A consensus algorithm was applied to determine the allocated proportions of exported or imported electricity and natural gas for each DMES in a distributed way. An IEDS including five DMESs was used as a test system. The results of the case studies demonstrate the effectiveness of the proposed hierarchical management strategy and algorithm.
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7

Šadibolová, Michaela, Tomáš Zárybnický, Tomáš Smutný, Petr Pávek, Zdeněk Šubrt, Petra Matoušková, Lenka Skálová, and Iva Boušová. "Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver." International Journal of Molecular Sciences 20, no. 18 (September 14, 2019): 4562. http://dx.doi.org/10.3390/ijms20184562.

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Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) on the expression of four phase I DMEs (cytochrome P450 3A4 and 2C, carbonyl reductase 1, and aldo-keto reductase 1C) at both the mRNA and protein levels. For this purpose, human precision-cut liver slices (PCLS) prepared from 10 patients and transfected HepG2 cells were used. Western blotting, quantitative real-time PCR and reporter gene assays were employed in the analyses. In the reporter gene assays, all sesquiterpenes significantly induced cytochrome P450 3A4 expression via pregnane X receptor interaction. However in PCLS, their effects on the expression of all the tested DMEs at the mRNA and protein levels were mild or none. High inter-individual variabilities in the basal levels as well as in modulatory efficacy of the tested sesquiterpenes were observed, indicating a high probability of marked differences in the effects of these compounds among the general population. Nevertheless, it seems unlikely that the studied sesquiterpenes would remarkably influence the bioavailability and efficacy of concomitantly administered drugs.
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8

Slámka, M. "Real Time Dispatch Training Simulator based on TRIS/DMES ELEKTROSYSTEM." IFAC-PapersOnLine 49, no. 27 (2016): 201–6. http://dx.doi.org/10.1016/j.ifacol.2016.10.683.

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9

Shao, Yun-yun, Jing Huang, Yan-rong Ma, Miao Han, Kang Ma, Hong-yan Qin, Zhi Rao, and Xin-an Wu. "Serum serotonin reduced the expression of hepatic transporter Mrp2 and P-gp via regulating nuclear receptor CAR in PI-IBS rats." Canadian Journal of Physiology and Pharmacology 93, no. 8 (August 2015): 633–39. http://dx.doi.org/10.1139/cjpp-2015-0039.

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Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated. To further clarify the underlying mechanism, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the 5-HT depleting agent parachlorophenylalanine (pCPA) were applied to adjust serum levels of 5-HT. Serum levels of 5-HT were measured using LC-MS/MS; the expression of hepatic transporters, DMEs, and nuclear receptors were examined by Western-blot technique. Our results showed that in PI-IBS rats the expression of multidrug resistance protein 2 (Mrp2) was significantly decreased, while colonic enterochromaffin cell density and serum levels of 5-HT were all significantly increased. Moreover, 5-HTP treatment significantly increased serum levels of 5-HT and decreased the expression of Mrp2 and glycoprotein P (P-gp), whereas treatment with pCPA markedly decreased serum levels of 5-HT and increased the expression of Mrp2 and P-gp. Our results indicated that serum 5-HT regulates the expression of Mrp2 and P-gp, and the underlying mechanism may be related to the altered expression of the nuclear receptor constitutive androstane receptor (CAR).
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10

Prasad, Bhagwat. "Quantitative analysis of hepatic transporters and DMEs during growth and development." Drug Metabolism and Pharmacokinetics 32, no. 1 (January 2017): S12. http://dx.doi.org/10.1016/j.dmpk.2016.10.060.

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11

Sarsaiya, Surendra, Archana Jain, Qi Jia, Xiaokuan Fan, Fuxing Shu, Zhongwen Chen, Qinian Zhou, Jingshan Shi, and Jishuang Chen. "Molecular Identification of Endophytic Fungi and Their Pathogenicity Evaluation Against Dendrobium nobile and Dendrobium officinale." International Journal of Molecular Sciences 21, no. 1 (January 2, 2020): 316. http://dx.doi.org/10.3390/ijms21010316.

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Dendrobium are tropical orchid plants that host diverse endophytic fungi. The role of these fungi is not currently well understood in Dendrobium plants. We morphologically and molecularly identified these fungal endophytes, and created an efficient system for evaluating the pathogenicity and symptoms of endophytic fungi on Dendrobium nobile and Dendrobium officinale though in vitro co-culturing. ReThe colony morphological traits of Dendrobium myco-endophytes (DMEs) were recorded for their identification. Molecular identification revealed the presence of Colletotrichum tropicicola, Fusarium keratoplasticum, Fusarium oxysporum, Fusarium solani, and Trichoderma longibrachiatum. The pathogenicity results revealed that T. longibrachiatum produced the least pathogenic effects against D. nobile protocorms. In seedlings, T. longibrachiatum showed the least pathogenic effects against D. officinale seedlings after seven days. C. tropicicola produced highly pathogenic effects against both Dendrobium seedlings. The results of histological examination of infected tissues revealed that F. keratoplasticum and T. longibrachiatum fulfill Koch’s postulates for the existence of endophytes inside the living tissues. The DMEs are cross-transmitted inside the host plant cells, playing an important role in plant host development, resistance, and alkaloids stimulation.
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Jeníček, V. "Developing countries – trends, differentiation." Agricultural Economics (Zemědělská ekonomika) 57, No. 4 (May 4, 2011): 175–84. http://dx.doi.org/10.17221/77/2010-agricecon.

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Socio-economic backwardness is usually defined by common characteristics or classification. The differences between the DMEs and DCs in the case of resources (prevalence of DCs) and in the case of outputs and performance (prevalence of DMEs) is evident. The difference in the economic level and the level of living between the DCs and DMEs had deepened during the last three decades, however, it has to be pointed out again, that this difference is increasing still more slowly what can be a presage of an approaching turn (in the sense of the possible beginning of a slow decrease of this gap). While the per capita GDP indicator is regarded as one of the most important indicators of the economic level, the HDI can be regarded as the most important indicator of the given country population level of living and as such, it is hitherto rather underestimated. Similarly, the CPM indicator (as the measure of poverty), which is a composed indicator, has a higher testifying ability than a simple income level per capita in USD defined as the poverty level. It is obvious, that economic development is impossible without social development, and vice versa. Generally, the gap between the more developed developing countries, measured through the world income distribution, is then still widening. As a positive phenomenon, there can be, however, regarded the fact that deepening of this gap occurs at a lower rate. Through a more detailed analysis by the individual indicators, the most valuable from which are the indicators composed from several partial indicators (for example HDI, CPM), a certain tendencies towards the gradual improvement of the socio-economic situation in developing countries as a whole &ndash; but with the relevant differences in the individual regions of the world &ndash; can be discerned. In general, close ties have been proven between the economic growth and the growth of the population level of living, their mutual influencing and the main elements from which they are composed.
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Roberts, N. J., H. R. Burton, and G. A. Pitson. "Volatile organic compounds from Organic Lake, an Antarctic, hypersaline, meromictic lake." Antarctic Science 5, no. 4 (December 1993): 361–66. http://dx.doi.org/10.1017/s0954102093000483.

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Five volatile organic compounds were identified throughout 1991 in the hypolimnion of Organic Lake. These were dimethylsulphide (DMS), dimethyldisulphide (DM2S), dimethyltrisulphide (DM3S), dimethyltetrasulphide (DM4S) and phenol. The concentration of these compounds increased with lake depth. The concentration of DMS and DM2S was higher in the sediment than in the water column. Carbon disulphide occurred only in the sediment. DMS was the only volatile organic compound detected in the epilimnion of the lake, where its concentration increased from winter onwards. The source of DMS was not dimethylsulphoniopropionate (DMSP). This was determined by hydroxylation of the sample with NaOH. There was no change in the concentration of DMS but the concentration of DM2S increased dramatically while the concentrations of DM3S and DM4S decreased concomitantly. This has important implications in the estimation of DMS derived from DMSP by hydroxylation when organic polysulphides are also present. The stability of the hypolimnion of Organic Lake was reflected by the lack of change in temperature, density, redox potential and the relatively constant concentration of volatile organic compounds throughout the year. Potential sources of the volatile organic compounds are discussed in relation to the isolated nature of the lake.
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Abdullah, Nurul, and Sabariah Ismail. "Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents." Molecules 23, no. 10 (October 19, 2018): 2696. http://dx.doi.org/10.3390/molecules23102696.

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The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated. Zidovudine (ZDV) was used as the probe substrate to determine UGT2B7 activity. The intrinsic clearance (Vmax/Km) of ZDV in HLM is 1.65 µL/mg/min which is ten times greater than in RLM, which is 0.16 µL/mg/min. Andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone inhibited ZDV glucuronidation in HLM with IC50 values of 6.18 ± 1.27, 18.56 ± 8.62, 8.11 ± 4.48 and 4.57 ± 0.23 µM, respectively, hence, herb-drug interactions are possible if andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone are taken together with drugs that are highly metabolized by UGT2B7. Meanwhile, only mitragynine and zerumbone inhibited ZDV glucuronidation in RLM with IC50 values of 51.20 ± 5.95 μM and 8.14 ± 2.12 µM, respectively, indicating a difference between the human and rat microsomal model so caution must be exercised when extrapolating inhibitory metabolic data from rats to humans.
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Lim, Yun-Ping, Chia-Yun Ma, Cheng-Ling Liu, Yu-Hsien Lin, Miao-Lin Hu, Jih-Jung Chen, Dong-Zong Hung, Wen-Tsong Hsieh, and Jin-Ding Huang. "Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–15. http://dx.doi.org/10.1155/2012/242810.

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Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.
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Follman, Kristin, and Marilyn Morris. "Simulation-Based Analysis of the Impact of Renal Impairment on the Pharmacokinetics of Highly Metabolized Compounds." Pharmaceutics 11, no. 3 (March 2, 2019): 105. http://dx.doi.org/10.3390/pharmaceutics11030105.

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Renal impairment (RI) is a highly prevalent disease which can alter the pharmacokinetics (PK) of xenobiotics, including those that are predominately metabolized. The expression and activity of drug metabolizing enzymes (DMEs) and protein binding of compounds has been demonstrated to be affected in RI. A simulation based approach allows for the characterization of the impact of changes in these factors on the PK of compounds which are highly metabolized and allows for improved prediction of PK in RI. Simulations with physiologically based pharmacokinetic (PBPK) modeling was utilized to define the impact of these factors in PK in RI for a model substrate, nifedipine. Changes in fraction unbound and DME expression/activity had profound effects on PK in RI. Increasing fraction unbound and DME expression resulted in a reduction in exposure of nifedipine, while the reduction of DME activity resulted in an increase in exposure. In vitro and preclinical data were utilized to inform simulations for nifedipine, sildenafil and zidovudine. Increasing fraction unbound and changes in the expression/activity of DMEs led to improved predictions of PK. Further characterization of the impact of RI on these factors is warranted in order to better inform a priori predictions of PK in RI.
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Brenet, Fabienne, Michelle Moh, Patricia Funk, Daoqui You, Agnes J. Viale, Nicholas D. Socci, and Joseph M. Scandura. "Genome-Wide Analysis of DNA Methylation Patterns Reveals Dynamic Epigenetic Regulation of the AML Genome After Decitabine Treatment." Blood 114, no. 22 (November 20, 2009): 591. http://dx.doi.org/10.1182/blood.v114.22.591.591.

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Abstract Abstract 591 The human genome is adorned with methylated cytosine residues that function in the epigenetic guidance of cellular differentiation and development. Cellular interpretation of this epigenetic mark is incompletely understood and tissue specific patterns of DNA methylation vary with age, can be altered by environmental factors, and are often abnormal in human disease. Aberrant DNA methylation is a common means by which tumor suppressor genes (TSGs) are inactivated during carcinogenesis (Baylin, Herman, Graff, Vertino and Issa 1998; Laird and Jaenisch 1996; Singal and Ginder 1999). Unlike genetic mechanisms of gene inactivation, such as gene deletion and mutation, the epigenetic silencing of TSGs by promoter hypermethylation is potentially reversible. This has led to the broad interest of cancer biologists in the study of DNA methylation. Method: We developed a method for genome-wide analysis of DNA methylation by using a recombinant protein containing a methyl-CpG binding domain (MBD) to enrich methylated DNA fragments that are then identified by massively parallel sequencing using the SOLiD sequencer (ABI). We generated ∼15-million sequence tags per specimen and wrote custom R-language algorithms to develop an analytical platform with which to study DNA methylation. We used this technology to study the pharmacodynamics of DNA methylation in acute myelogenous leukemia (AML) cells following exposure to the hypomethylating agent, 5-aza-2'-deoxycytidine (decitabine). We compared DNA methylation patterns before and after decitabine treatment with transcriptional activity revealed by microarrays (Illumina) and quantitative PCR. We found that Sequence Tag Analysis of Methylation Profiles (STAMP) permits highly reproducible, genome-wide identification of DNA methylation density at near base-pair resolution. This method is cost effective and can be extended, without modification, to any mapped genome. Results: STAMP analysis revealed patterned DNA methylation at all scales across the genome: from whole chromosomes to individual genes. We found that densely methylated elements (DMEs) of the human genome are often highly conserved or closely associated with gene coding regions and promoters. We identified distinct patterns of DNA methylation surrounding the transcription start and termination sites of all genes. These methylation patterns are associated with transcriptional activity of neighboring genes. Interestingly, genes with a densely methylated transcription start site (TSS) have little methylation in the surrounding regions whereas genes with little or no methylation at the TSS have disproportionately higher methylation within their gene bodies. In untreated cells, we detected ∼75,000 DMEs (false discovery rate <0.01) with a median length ∼600 bp and with 75% being less than 960bp. The longest DMEs extend up to ∼24000 bp and are composed of microsatellite clusters. The majority of the DMEs are not classic CpG islands (CGI) but are GC-rich regions (median 57% GC) with a greater than expected incidence of CpG dinucleotides (median CpG observed/expected 0.49): results that suggest the definition of a CGI excludes the majority of the methylated human genome. Although the pattern of DNA methylation was qualitatively similar in cells treated with decitabine, we found that the density of methylation was generally lower and fewer DMEs (∼50,000) were identified. Decitabine treatment led to increased expression of ∼800 genes involved in cell cycle control, apoptosis and cellular differentiation whereas the ∼50 genes with downregulated expression were most commonly involved in RNA metabolism. Distinct pre-treatment DNA methylation patterns were associated with, and tended to predict, the transcriptional activity following treatment with decitabine. Summary: We developed and utilized a powerful new technology to uncover the genome-wide effects of decitabine on DNA methylation patterns in AML. We found that although decitabine induces genome-wide DNA hypomethylation, its effect on transcription depends upon the pattern of DNA methylation prior to treatment. The STAMP methodology leverages the power and flexibility of massively parallel sequencing with the high selectivity of the MBD for its natural ligand, methyl-CpG. This assay permits robust, unbiased and highly sensitive whole-genome identification of methylated DNA segments. Disclosures: No relevant conflicts of interest to declare.
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Raju, Baddipadige, Shalki Choudhary, Gera Narendra, Himanshu Verma, and Om Silakari. "Molecular modeling approaches to address drug-metabolizing enzymes (DMEs) mediated chemoresistance: a review." Drug Metabolism Reviews 53, no. 1 (January 2, 2021): 45–75. http://dx.doi.org/10.1080/03602532.2021.1874406.

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19

Wang, Xiao, and Haja N. Kadarmideen. "Characterization of Global DNA Methylation in Different Gene Regions Reveals Candidate Biomarkers in Pigs with High and Low Levels of Boar Taint." Veterinary Sciences 7, no. 2 (June 13, 2020): 77. http://dx.doi.org/10.3390/vetsci7020077.

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DNA methylation of different gene components, including different exons and introns, or different lengths of exons and introns is associated with differences in gene expression. To investigate the methylation of porcine gene components associated with the boar taint (BT) trait, this study used reduced representation bisulfite sequencing (RRBS) data from nine porcine testis samples in three BT groups (low, medium and high BT). The results showed that the methylation levels of the first exons and first introns were lower than those of the other exons and introns. The first exons/introns of CpG island regions had even lower levels of methylation. A total of 123 differentially methylated promoters (DMPs), 194 differentially methylated exons (DMEs) and 402 differentially methylated introns (DMIs) were identified, of which 80 DMPs (DMP-CpGis), 112 DMEs (DME-CpGis) and 166 DMIs (DMI-CpGis) were discovered in CpG islands. Importantly, GPX1 contained one each of DMP, DME, DMI, DMP-CpGi, DME-CpGi and DMI-CpGi. Gene-GO term relationships and pathways analysis showed DMP-CpGi-related genes are mainly involved in methylation-related biological functions. In addition, gene–gene interaction networks consisted of nodes that were hypo-methylated GPX1, hypo-methylated APP, hypo-methylated ATOX1, hyper-methylated ADRB2, hyper-methylated RPS6KA1 and hyper-methylated PNMT. They could be used as candidate biomarkers for reducing boar taint in pigs, after further validation in large cohorts.
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Kim, Euiho. "Analysis of DME/DME Navigation Performance and Ground Network Using Stretched-Front-Leg Pulse-Based DME." Sensors 18, no. 10 (September 29, 2018): 3275. http://dx.doi.org/10.3390/s18103275.

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Global navigation satellite systems (GNSS) have become a primary navigation means for aircraft. However, the signal power of GNSS is very weak, and its service can be disrupted at any time when there is interference or jamming. For this reason, the Federal Aviation Administration (FAA) in the United States has recently chosen a distance measuring equipment (DME)-based aircraft navigation technique, called DME/DME, as an alternative aircraft navigation means for use by around 2030. The reason that the FAA plans to use DME/DME in such a short duration, by around 2030, is presumed to be because the ranging accuracy of DMEs is between 70 to 300 m, which is about 7 to 30 times worse than that of GNSS. Thus, a significant loss of positioning performance is unavoidable with current DMEs. To make DME/DME a more competent alternative positioning source, this paper proposes an advanced DME that could provide a ranging accuracy of around 30 m by employing a recently developed Stretched-Front-Leg (SFOL) pulse. The paper introduces optimal ground station augmentation algorithms that help to efficiently transform the current DME ground network to enable a DME/DME positioning accuracy of up to 0.3 nm or 92.6 m with a minimal number of new ground DME sites. The positioning performance and augmented ground network using the proposed SFOL pulse-based DME are evaluated in two regions which have distinct terrain conditions.
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Jeong, Hyesoo, Soolin Kim, Mi-yeon Kim, Jimin Lee, Byoung An, Hee-Doo Kim, Hyunyoung Jeong, Yun Song, and Minsun Chang. "Inhibitory and Inductive Effects of Opuntia ficus indica Extract and Its Flavonoid Constituents on Cytochrome P450s and UDP-Glucuronosyltransferases." International Journal of Molecular Sciences 19, no. 11 (October 30, 2018): 3400. http://dx.doi.org/10.3390/ijms19113400.

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Opuntia ficus indica (OFI) is grown abundantly in arid areas and its fruits are regarded as an important food and nutrient source owing to the presence of flavonoids, minerals, and proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements to be used as alternative estrogen replacement therapy. In the case of polypharmacy with the consumption of OFI-containing botanicals in post- or peri-menopausal women, it is critical to determine the potential drug-OFI interaction due to the modulation of drug metabolism. In the present study, the modulating effects on the hepatic drug metabolizing enzymes (DMEs) by OFI and its flavonoid constituents (kaempferol, quercetin, isorhamnetin, and their glycosidic forms) were investigated using the liver microsomal fractions prepared from ovariectomized (OVX) rats, human liver microsomes, and human hepatocarcinoma cell line (HepG2). As a result, the oral administration of extracts of OFI (OFIE) in OVX rats induced hepatic CYP2B1, CYP3A1, and UGT2B1. OFIE, hydrolyzed (hdl) OFIE, and several flavonols induced the transcriptional activities of both CYP2B6 and CYP3A4 genes in HepG2 cells. Finally, OFIE did not inhibit activities of cytochrome P450 (CYPs) or uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), whereas hdl OFIE or flavonol treatment inhibited CYP1A2 and CYP3A1/3A4 in rat and human liver microsomes. Our data demonstrate that OFIE may induce or inhibit certain types of DMEs and indicate that drug-OFI interaction may occur when the substrate or inhibitor drugs of specific CYPs or UGTs are taken concomitantly with OFI-containing products.
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He, Xi Jun, Hirofumi Yamauchi, Kazuhiko Suzuki, Masaki Ueno, Hiroyuki Nakayama, and Kunio Doi. "Gene expression profiles of drug-metabolizing enzymes (DMEs) in rat liver during pregnancy and lactation." Experimental and Molecular Pathology 83, no. 3 (December 2007): 428–34. http://dx.doi.org/10.1016/j.yexmp.2006.05.002.

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Eeckhoutte, C., A. Giuliano Albo, M. Carletti, A. Rossetto Giaccherino, P. Galtier, C. Nebbia, and M. Dacasto. "Time-dependent variations of drug-metabolising enzyme activities (DMEs) in primary cultures of rabbit hepatocytes." Toxicology in Vitro 16, no. 4 (August 2002): 375–82. http://dx.doi.org/10.1016/s0887-2333(02)00018-8.

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Kymionis, George D., Dimitrios A. Liakopoulos, Michael A. Grentzelos, Irini Naoumidi, Georgios A. Kontadakis, Konstantinos I. Tsoulnaras, and Myrsini K. Petrelli. "Mini descemet membrane stripping (m-DMES) in patients with Fuchs’ endothelial dystrophy: A new method." Saudi Journal of Ophthalmology 31, no. 4 (October 2017): 275–79. http://dx.doi.org/10.1016/j.sjopt.2017.05.010.

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Louvain, Nicolas, Nicolas Mercier, and Florent Boucher. "α- to β-(dmes)BiI5(dmes = Dimethyl(2-ethylammonium)sulfonium Dication): Umbrella Reversal of Sulfonium in the Solid State and Short I···I Interchain ContactsCrystal Structures, Optical Properties, and Theoretical Investigations of 1D Iodobismuthates." Inorganic Chemistry 48, no. 3 (February 2, 2009): 879–88. http://dx.doi.org/10.1021/ic801900r.

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Buchshtav, Tamir, Alon Amrani, Ward Said-Ahmad, and Alexey Kamyshny Jr. "Kinetics and mechanism of the abiotic decomposition of dimethyl polysulfides with three, four and five sulfur atoms under dark, oxic conditions." Environmental Chemistry 16, no. 7 (2019): 495. http://dx.doi.org/10.1071/en19076.

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Environmental contextDimethyl polysulfides are malodorous compounds formed from decomposing algal matter. The decomposition of dimethylpolysulfides with 3–5 sulfur atoms was studied in aqueous solution under dark, oxygenated conditions and compared with observations of natural systems. The half-lives of dimethyl tri- and tetrasulfides are very long (176–100000 years), while the half-life of dimethyl pentasulfide (&lt;2 years) is similar to the observed time of its removal from natural aquatic systems. AbstractThe presence of malodorous dimethyl polysulfides (DMPSs) has been documented in various aquatic systems. In this work, we studied the kinetics and mechanisms of the chemical decomposition of DMPSs with 3–5 sulfur atoms in aqueous solutions in the presence of oxygen and absence of light. DMPSs are shown to undergo reaction with hydroxyl ions, which results in their decomposition. The orders of the decomposition reactions with respect to dimethyl trisulfide (DMTS), dimethyl tetrasulfide (DM4S) and dimethyl pentasulfide (DM5S) are 2.0±0.3, 1.7±0.3 and 2.0±0.2, respectively. The reaction orders with respect to OH− are 0.59±0.06, 0.56±0.08 and 0.58±0.11, respectively. The activation energies of these reactions are 170kJmol−1K−1, 114kJmol−1K−1 and 75kJmol−1K−1, respectively. The initial products of the decomposition are Me2Sn−1 and Me2Sn+1 and the apparent final products are elemental sulfur and dimethyl disulfide (DMDS). DMDS, which is formed during the decomposition of DMTS, is depleted in 34S (ϵ=−13.2 ‰), while the DM4S is enriched 34S (ϵ=4.7 ‰). A mechanism for the decomposition of DMPSs is proposed based on the results. Under these conditions, half-lives for the decomposition of DMPSs in Lake Kinneret vary from 2 months for DM5S to 100000 years for DMTS. The relatively short time scale of the reported odour episodes indicates that other chemical, photochemical or biological processes are responsible for the decomposition of DMTS and DM4S.
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Li, Zhefei, Xiuyong Song, Juanjuan Wang, Xiaoli Bai, Engting Gao, and Gehong Wei. "Nickel and cobalt resistance properties of Sinorhizobium meliloti isolated from Medicago lupulina growing in gold mine tailing." PeerJ 6 (July 10, 2018): e5202. http://dx.doi.org/10.7717/peerj.5202.

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Sinorhizobium meliloti CCNWSX0020, isolated from root nodules of Medicago lupulina growing in gold mine tailings in the northwest of China, displayed multiple heavy metal resistance and growth promotion of M. lupulina. In our previous work, the expression level of dmeR and dmeF genes were induced by Cu2+ through comparative transcriptome approach. Based on protein analysis, the dmeF encoded for a protein which showed a 37% similarity to the cation transporter DmeF of Cupriavidus metallidurans, whereas dmeR encoded transcriptional regulator which was highly homologous with DmeR belonging to RcnR/CsoR family metal-responsive transcriptional regulator. In addition to copper, quantitative real-time PCR analysis showed that dmeR and dmeF were also induced by nickel and cobalt. To investigate the functions of dmeR and dmeF in S. meliloti CCNWSX0020, the dmeR and dmeF deletion mutants were constructed. The dmeF mutant was more sensitive to Co2 + and Ni2 + than the wild type strain. Pot experiments were carried out to determine whether the growth of M. lupulina was affected when the dmeF gene was knocked out in the presence of nickel or cobalt. Results indicated that the nodule number of the host plant inoculated with the dmeF deletion mutant was significantly less than the S. meliloti CCNWSX0020 wild-type in the presence of Co2 + or Ni2 +. However, when standardized by nodule fresh weight, the nitrogenase activities of nodules infected by the dmeF deletion mutant was similar to nitrogenase activity of the wild type nodule.
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Kıran, Jiyan. "Expanding the framework of the varieties of capitalism: Turkey as a hierarchical market economy." Journal of Eurasian Studies 9, no. 1 (January 2018): 42–51. http://dx.doi.org/10.1016/j.euras.2017.12.004.

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This article both extends the debate on the varieties of capitalism theory beyond the existing literature to solve the ambiguous position of the variety of capitalism that is found in Turkey and brings a novel approach to the studies of the political economy of Turkey by adopting a firm-centred position using the varieties of capitalism framework. Based on a qualitative comparison with the dependent market economies (DMEs), mixed market economies (MMEs) and hierarchical market economies (HMEs), this article claims that Turkey is a hierarchical market economy with four characteristic features that are also found in Latin American economies. These core features are the dominance of the family-owned diversified business groups, state-regimented and weak industrial relations, low skills and the influence of MNCs.
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Eugene, Andy R. "Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors." PeerJ 7 (October 9, 2019): e7860. http://dx.doi.org/10.7717/peerj.7860.

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Background Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed class of drugs in the practice of psychiatry. Cytochrome P450 (CYP) 2C19 and CYP2D6 are established as clinically relevant drug metabolizing enzymes (DMEs) that influence the pharmacokinetics of SSRIs and may either be grouped as being primarily metabolized by CYP2C19 or CYP2D6. The aim of this study is to test the hypothesis that the primary drug metabolizing pathway for SSRI antidepressants are associated with adverse drug reactions (ADRs) related to physiological modulation of organs with the highest gene tissue expression. Methods Post-marketing ADR cases were obtained from the United States Food and Drug Administration’s Adverse Events Reporting System from each of the four quarters for the years 2016 and 2017. Cases were grouped based on one of two primary pharmacokinetic pharmacogenomic pathway biomarkers CYP2C19 and CYP2D6. Citalopram, escitalopram, and sertraline were grouped as CYP2C19 substrates and fluvoxamine, fluoxetine, and paroxetine as CYP2D6 substrates. Logistic regression was computed for the reported SSRI ADRs associated with one of two aforementioned DMEs. All data homogenization and computations were performed in R for statistical programming. Results The most commonly reported ADR among the SSRIs was anxiety (n = 3,332). The top two ADRs associated with SSRIs metabolized by CYP2D6 are: nightmare (n = 983) reporting odds-ratio (OR) = 4.37 (95% confidence interval (CI) [3.67–5.20]) and panic attack (n = 1,243) OR = 2.43 (95% CI [2.11–2.79]). Contrastingly, the top two ADRs for CYP2C19 metabolized SSRIs are: electrocardiogram QT prolonged (n = 351) OR = 0.18 (95% CI [0.13–0.24]) and small for dates baby (n = 306) OR = 0.19 (95% CI [0.14–0.26]). The study tested and produced 40 statistically significant CYP2C19- and CYP2D6-biased ADRs. In overall context, the results suggest that CYPC19 SSRI substrates are associated with ADRs related to modulation of the autonomic nervous system, seizure, pain, erectile-dysfunction, and absorption. Contrastingly, CYP2D6 SSRI substrates are associated with ADRs related to nightmares, withdrawal syndrome, and de-realization of cognitive processes. The results of this study may aid as guidance to optimize drug selection in psychopharmacology.
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Li, Jian, Man Wu, Keru Wang, Bo Ming, Xiao Chang, Xiaobo Wang, Zhaosheng Yang, Ruizhi Xie, and Shaokun Li. "Identifying Ways to Narrow Maize Yield Gaps Based on Plant Density Experiments." Agronomy 10, no. 2 (February 16, 2020): 281. http://dx.doi.org/10.3390/agronomy10020281.

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Exploring the maximum grain yields (GYs) and GY gaps in maize (Zea mays L.) can be beneficial for farmer to identify the GY-limiting factors and take adaptive management practices for a higher GY. The objective of this work was to identify the optimum maize plant density range and the ways to narrow maize GY gaps based on the variation of the GYs, dry matter (DM) accumulation and remobilization with changes in plant density. Field experiments were performed at the 71 Group and Qitai Farm in Xinjiang, China. Two modern cultivars, ZhengDan958 and ZhongDan909, were planted at 12 densities, ranging from 1.5 to 18 plants m−2. With increased plant density, single plant DM decreased exponentially, whereas population-level DM at the pre- (DMBS) and post- (DMAS) silking stages increased, and the amount of DM remobilization (ARDM) increased exponentially. Further analysis showed that plants were divided four density ranges: range I (<6.97 plants m−2), in which no DM remobilization occurred, DMBS and DMAS correlated significantly with GY; range II (6.97–9.54 plants m−2), in which the correlations of DMBS, DMAS, and ARDM with GY were significant; range III (9.54–10.67 plants m−2), in which GY and DMAS were not affected by density, DMBS increased significantly, and only the correlation of DMAS with GY was significant; and range IV (>10.67 plants m−2), in which the correlations of DMBS and ARDM with GY decreased significantly, while that of DMAS increased significantly. Therefore, ranges I and II were considered to be DM-dependent ranges, and a higher GY could be obtained by increasing the population-level DMAS, DMAS, and ARDM. Range III was considered the GY-stable range, increasing population-level DMBS, as well as preventing the loss of harvest index were the best way to enhance maize production. Range IV was interpreted as the GY-loss range, and a higher GY could be obtained by preventing the loss of HI and population-level DMAS.
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Baumal, Caroline. "EFFECT OF RUBOXISTAURIN IN PATIENTS WITH DIABETIC MACULAR EDEMA: THIRTY-MONTH RESULTS OF THE RANDOMIZED PKC-DMES CLINICAL TRIAL." Evidence-Based Ophthalmology 8, no. 4 (October 2007): 208–9. http://dx.doi.org/10.1097/ieb.0b013e318156a7f3.

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Buchshtav, Tamir, and Alexey Kamyshny. "Decomposition of dimethyl polysulfides under solar irradiation in oxic aqueous solutions." Environmental Chemistry 17, no. 5 (2020): 377. http://dx.doi.org/10.1071/en19252.

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Environmental contextThe quality of drinking water can be greatly compromised by the presence of dimethyl polysulfides. We studied the rate and mechanism of decomposition of dimethyl polysulfides in aqueous solution under solar irradiation, and found that they decompose photochemically in seconds to minutes, i.e. much faster than under dark conditions. These results suggest that photochemical pathways of dimethyl polysulfide decomposition may prevail in euphotic zones of natural aquatic systems. AbstractThe presence of malodorous dimethyl polysulfides (DMPSs) has been documented in marine and limnic systems as well as in tap water distribution systems. These compounds compromise the quality of drinking water. Under oxic conditions and in the absence of radiation, DMPSs with n ≥ 3 sulfur atoms disproportionate into DMPSs with n+1 and n−1 sulfur atoms, and, finally, to dimethyl disulfide (DMDS) and S8. DMDS, in turn, decomposes to methyl mercaptan (MT) and methanesulfinic acid. Under these conditions, the half-lives of DMPSs vary from months for dimethyl pentasulfide (DM5S) to hundreds of thousands of years for DMDS. In this work, we studied the kinetics and mechanisms of the decomposition reactions of DMPSs with 2–5 sulfur atoms in aqueous solutions in the presence of oxygen and under exposure to solar radiation. The quantum yields of decomposition of DMPSs with 2, 3, 4 and 5 sulfur atoms do not depend on either the concentration of DMPSs or pH, and are 40±10, 2.0±0.2, 35±10 and 10±4 respectively. The quantum yields, which are higher than unity, suggest that under exposure to solar radiation the photochemical decomposition of DMPSs proceeds by a radical chain reaction mechanism. Half-lives of DMPSs in oxic aquatic solutions exposed to solar radiation under a very clear atmosphere and a solar elevation angle of 90° were calculated from the quantum yields and were found to be as low as 43±13s for DMDS, 40±4s for dimethyl trisulfide (DMTS), 2.1±0.6s for dimethyl tetrasulfide (DM4S) and 4.2±1.7s for DM5S.
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Nölke, Andreas, and Arjan Vliegenthart. "Enlarging the Varieties of Capitalism: The Emergence of Dependent Market Economies in East Central Europe." World Politics 61, no. 4 (August 26, 2009): 670–702. http://dx.doi.org/10.1017/s0043887109990098.

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This article enlarges the existing literature on the varieties of capitalism by identifying a third basic variety that does not resemble the liberal market economy or coordinated market economy types. The dependent market economy (DME) type, as it is named by the authors, is characterized by the importance of foreign capital for the socioeconomic setup and is located in postsocialist Central Europe. Since the collapse of state socialism in the late 1980s, the Czech Republic, Hungary, Poland, and the Slovak Republic have introduced a rather successful model of capitalism when compared with other postsocialist states. This article identifies the key elements of the DME model and discusses their interplay. DMEs have comparative advantages in the assembly and production of relatively complex and durable consumer goods. These comparative advantages are based on institutional complementarities between skilled, but cheap, labor; the transfer of technological innovations within transnational enterprises; and the provision of capital via foreign direct investment.
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Shelepova, T., A. N. Nafziger, J. Victory, A. D. Kashuba, E. Rowland, Y. Zhang, E. Sellers, et al. "Effect of oral contraceptives (OCS) on drug metabolizing enzymes (DMES) as measured by the validated cooperstown 5+1 cocktail (5+1)." Clinical Pharmacology & Therapeutics 73, no. 2 (February 2003): P14. http://dx.doi.org/10.1016/s0009-9236(03)90408-5.

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35

Oganesyan, Oganes G., A. A. Grdikanyan, S. S. Yakovleva, and V. R. Getadaryan. "THE PARTIAL DESCEMET'S STRIPPING WITH TRANSPLANTATION OF DESCEMET'S TRANSPLANT UNDER ENDOTHELIAL DYSTROPHY OF CORNEA." Medical Journal of the Russian Federation 23, no. 5 (October 15, 2017): 248–53. http://dx.doi.org/10.18821/0869-2106-2017-23-5-248-253.

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The DMEK technique is applied five times more rarely than DS(A)EK despite that DMEK provides higher functional result. The main causes are technical "convolution" of implementation, long period of training, accompanied by prolonged operations, higher reject control of donor's tissue, increased rate of dependency of endothelium and mismatch of transplant. Therefore, an efficient technique is needed similar to DMEK though simpler than DMEK.The purpose of study. To analyze the results of implantation of Descemet's transplant (DMET) in patients with endothelium dystrophy of cornea (Fuchs) on the basis of limited clinical observations.Material of study. In two years, DMET was implemented to 12 patients. The study included 6 patients with average age of 60±18 years (from 29 to 80 years). All female patients had primary endothelial dystrophy and one male patient had secondary endothelial dystrophy. The visual acuity prior to DMET in average made up to 0,2±0,2 (from 0,01 to 0,5). The average CTR according optical coherent eye tomography made up to 685±53 µm (from 622 to 749 µm). Results. Within available periods of observation, resorption of edema of cornea takes place in 4 patients (67%) and visual acuity increased from average 0,2±0,1 to 0,45±0,3. In various periods density of endothelium cells varied from 549 to 689 kl per mm2. The indices of optical coherent eye tomography decreased from pre-operational 685±53 µm to 553±15 µm. Conclusion. The results testify efficiency of DMET. The period of restoration of transparency of cornea can vary from 1 to 6 months. The indices of density of endothelium cells are inferior to indices after DMEK. Also, DMET is ineffective in case of secondary dystrophy and at most efficient on previously non-operated eyes.
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Nestorovska, Kapedanovska A., K. Jakovski, Z. Naumovska, Hiljadnikova M. Bajro, Z. Sterjev, A. Eftimov, Matevska N. Geskovska, et al. "Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia." Balkan Journal of Medical Genetics 17, no. 2 (December 1, 2014): 5–14. http://dx.doi.org/10.2478/bjmg-2014-0069.

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Abstract Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response. This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations. Our findings define the population of the Republic of Macedonia as an ethnic group with a highly polymorphic genetic profile. These results add to the evidence regarding the distribution of clinically important variant alleles in DME and drug target genes in populations of European ancestry.
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Eldem, Bora, Sengul Ozdek, Ali Osman Saatci, Emin Ozmert, Esat Ulay, and Gulsah Nomak. "Clinical Characteristics of Patients with Newly Diagnosed Diabetic Macular Edema in Turkey: A Real-Life Registry Study—TURK-DEM." Journal of Ophthalmology 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/3596817.

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Purpose. To evaluate the clinical and diagnostic characteristics of patients with newly diagnosed diabetic macular edema (DME) in Turkey in a real-life setting. Methods. A total of 945 consecutive patients (mean (SD) age: 61.3 (9.9) years, 55.2% male) with newly diagnosed DME were included. Data on patient demographics, comorbidities, ocular history, ophthalmic examination findings including type of DME, central macular thickness (CMT) via time domain (TD) and spectral domain (SD) optical coherence tomography (OCT), and planned treatments were recorded. Results. OCT (98.8%) and fundoscopy (92.9%) were the two most common diagnostic methods. Diffuse and focal DMEs were detected in 39.2% and 36.9% of cases, respectively. Laser photocoagulation (32.1%) and antivascular endothelial growth factors (anti-VEGF; 31.8%) were the most commonly planned treatments. The median CMT in the right eye was significantly greater in untreated than in treated patients [376.5 μm (range: 160–840) versus 342 μm (range: 146–999) (p=0.002)] and in the left eye [370 μm (range: 201–780) versus 329 μm (range: 148–999) (p<0.001)]. Conclusions. This study is the first large-scale real-life registry of DME patients in Turkey. SD-OCT and fundoscopy were the most common diagnostic methods. Laser photocoagulation and anti-VEGF therapy were the most common treatments.
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Dmitriev, Alexander V., Alexey A. Lagunin, Dmitry А. Karasev, Anastasia V. Rudik, Pavel V. Pogodin, Dmitry A. Filimonov, and Vladimir V. Poroikov. "Prediction of Drug-Drug Interactions Related to Inhibition or Induction of Drug-Metabolizing Enzymes." Current Topics in Medicinal Chemistry 19, no. 5 (April 18, 2019): 319–36. http://dx.doi.org/10.2174/1568026619666190123160406.

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Drug-drug interaction (DDI) is the phenomenon of alteration of the pharmacological activity of a drug(s) when another drug(s) is co-administered in cases of so-called polypharmacy. There are three types of DDIs: pharmacokinetic (PK), pharmacodynamic, and pharmaceutical. PK is the most frequent type of DDI, which often appears as a result of the inhibition or induction of drug-metabolising enzymes (DME). In this review, we summarise in silico methods that may be applied for the prediction of the inhibition or induction of DMEs and describe appropriate computational methods for DDI prediction, showing the current situation and perspectives of these approaches in medicinal and pharmaceutical chemistry. We review sources of information on DDI, which can be used in pharmaceutical investigations and medicinal practice and/or for the creation of computational models. The problem of the inaccuracy and redundancy of these data are discussed. We provide information on the state-of-the-art physiologically- based pharmacokinetic modelling (PBPK) approaches and DME-based in silico methods. In the section on ligand-based methods, we describe pharmacophore models, molecular field analysis, quantitative structure-activity relationships (QSAR), and similarity analysis applied to the prediction of DDI related to the inhibition or induction of DME. In conclusion, we discuss the problems of DDI severity assessment, mention factors that influence severity, and highlight the issues, perspectives and practical using of in silico methods.
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Li, Jiapeng, and Hao-Jie Zhu. "Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters." Molecules 25, no. 11 (June 11, 2020): 2718. http://dx.doi.org/10.3390/molecules25112718.

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant to drug metabolism and disposition. Previous studies have consistently demonstrated marked interindividual variability in DMET protein expression, suggesting that varied DMET function is an important contributing factor for interindividual variability in pharmacokinetics (PK) and pharmacodynamics (PD) of medications. Moreover, differential DMET expression profiles were observed across different species and in vitro models. Therefore, caution must be exercised when extrapolating animal and in vitro DMET proteomics findings to humans. In recent years, DMET proteomics has been increasingly utilized for the development of physiologically based pharmacokinetic models, and DMET proteins have also been proposed as biomarkers for prediction of the PK and PD of the corresponding substrate drugs. In sum, despite the existence of many challenges in the analytical technology and data analysis methods of LC-MS/MS-based proteomics, DMET proteomics holds great potential to advance our understanding of PK behavior at the individual level and to optimize treatment regimens via the DMET protein biomarker-guided precision pharmacotherapy.
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Panozzo, Giacomo A., Elena Gusson, Giorgio Panozzo, and Giulia Dalla Mura. "Dexamethasone Intravitreal Implant at the Time of Cataract Surgery in Eyes with Diabetic Macular Edema." European Journal of Ophthalmology 27, no. 4 (December 16, 2016): 433–37. http://dx.doi.org/10.5301/ejo.5000920.

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Purpose To determine the potential role of intraoperative dexamethasone intravitreal implant (DEX-I) in reducing diabetic macular edema (DME) worsening after phacoemulsification. Methods This was a prospective study on 19 eyes of 19 patients with type 2 diabetes mellitus with DME and cataract. Mean preoperative Early Treatment Diabetic Retinopathy Study visual acuity (VA) was 16.7 letters. Mean foveal thickness (FT) was 451 μm. The DME was naive in 11 eyes and refractory in 8 eyes. All eyes underwent a standard phacoemulsification and intraocular lens implantation; DEX-I was injected at the end of surgery. Follow-up was performed at 1 week and then monthly until DME recurrence (up to 8 months). Results At 1 week, mean VA improved by 15 letters (range 0-29 letters) and mean FT decreased by 147 μm (range 69-236 μm). Improvement consolidated at month 1, with a mean VA improvement of 18 letters (range 3-32 letters) and a mean improvement in FT of 193 μm (range 76-304 μm), remaining stable at month 2 after surgery in all eyes. The DME recurred in 1 eye at month 3, in 14 eyes (73.8%) between months 4 and 5, and after month 6 in 4 eyes (21%). Refractory DMEs demonstrated the same benefit but recurred earlier than naive ones (4 months versus 5.8 months, p<0.01). Conclusions Intraoperative DEX-I prevents DME worsening after phacoemulsification. Its positive effects last for at least 3 months.
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Aggarwal, Himani, Hima Gupta, and Jhumur Sengupta. "Conditions of Unorganized Manufacturing Industries with Special Reference to MSMEs: A Field Study in Uttar Pradesh." Global Business Review 18, no. 6 (August 8, 2017): 1597–612. http://dx.doi.org/10.1177/0972150917713048.

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The study sets out to compare the three types of unorganized manufacturing units in India. These three enterprises are: own account manufacturing enterprises (OAMEs), it is the one which runs without any hired worker employed on a fairly regular basis and is engaged in manufacturing and/or repairing activities (with family labour only); non-directory manufacturing establishments (NDMEs), it is an establishment employing less than six workers (household and hired workers taken together) and is engaged in manufacturing activities; and directory manufacturing establishments (DMEs), it is the one which has employed six or more workers (household and hired workers taken together) and is engaged in manufacturing activities. The parameters for comparison are number of units, number of workers, wages, input, output and gross value added (GVA). The field survey of 500 unorganized manufacturing units has been conducted based on seven major manufacturing industries. Target respondents are the owners of the unorganized manufacturing units in Ghaziabad and Noida. An attempt is also made to measure the effect of labour market in unorganized manufacturing sector on its performance. Most of the studies on unorganized sector are based on the secondary data collected from National Sample Survey Organization. But this study is based on primary data collected with a help of structured questionnaire. The findings of the study help in determining the condition of these enterprises and lay down the idea which enterprise is relatively ahead and which is back with regard to various parameters. Independent sample t-test and multiple regression have also been conducted.
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42

Hynninen, Paavo H. "Protonation-deprotonation equilibria in tetrapyrroles Part 4: Mono- and diprotonations of deutero-, hemato-, meso-, and protoporphyrin IX dimethyl esters in methanolic hydrochloric acid." Journal of Porphyrins and Phthalocyanines 18, no. 05 (May 2014): 385–95. http://dx.doi.org/10.1142/s1088424614500126.

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The N-protonations in the deutero, hemato, meso and protoporphyrin IX dimethyl esters (DME) were investigated by spectrophotometric titrations using HCl as the acid and methanol as the solvent. Two spectroscopically different protonated species were observed for each porphyrin DME in addition to the neutral form. These were assigned to the N-protonated monocation and dication. There were no difficulties encountered in observing the monocation formation in the HCl – MeOH system. Very sharp isosbestic points were characteristic of each protonation stage. The p K3 values for the porphyrins in the above order were 3.23, 4.70, 2.93 and 3.37; the p K4 values were 2.48, 2.62, 2.41 and 2.64, respectively. For all porphyrins studied, no further spectral changes were observed after the dication was completely formed. This was interpreted as indicating that the formation of more highly protonated species is not possible in fullydelocalized porphyrins possessing the 18 π-electron [18]diazaannulene delocalization pathway. When the titration was performed on the free dicarboxylic acid porphyrins, aggregation obscured the first protonation step and no clear monocation spectrum could be distinguished. However, also in that case the titration ended up to a UVvis spectrum typical of the dication and the effect of aggregation on the p K4 values was negligible. The UVvis spectrometric parameters are given for the neutral forms and for the protonated species of the porphyrin DMEs. The results are discussed in terms of the NH tautomerization connected to the π-electron delocalization pathway (aromaticity), which tends to hinder outofplane distortions in the porphyrin plane, and in terms of solvation and counterion stabilization of the protonated forms.
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43

Kun, Sheila, Gregory Placencia, Sally Davidson Ward, and Thomas Keens. "A System Analysis of Delay in Outpatient Respiratory Equipment Delivery." Care Management Journals 17, no. 4 (December 2016): 161–69. http://dx.doi.org/10.1891/1521-0987.17.4.161.

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Objectives: To systematically assess barriers delaying home respiratory equipment requisition and to evaluate for temporal correlation between delays and emergency room or hospitalization episodes.Background: Initiation of home respiratory treatments is delayed because of delays in delivery of durable medical equipment (DME). This study assesses root causes of such delays from a system perspective. We also describe clinical consequences by measuring emergency room visits and hospitalization days for temporal correlations.Methods: We conducted a retrospective review of DME ordering records from April 2011 to March of 2012.Settings: Outpatient DME records in Pediatric Pulmonary Division.Results: Of 164 available orders studied, deliveries were made as followed: 31 (19%) within 24 hr: 18 (59%) oxygen orders and 10 (32%) nebulizer orders 50 (30%) within 1 week: 25 (50%) nebulizer orders and 10 (20%) oxygen orders Delays: 45 (27%) delivered > 1 month: Bilevel positive airway pressure (BPAP) = 16 (36%) Oxygen = 12 (26%) Cough assist device = 7 (16%) Nebulizer = 5 (11%) Miscellaneous devices = 5 (11%) Analysis of barriers includes (a) type of insurance, (b) human error, (c) communication barrier, (d) deficit in training or knowledge, (e) no clear policy, (f) differences in clinical policy/ standard, (g) no DME benefit, (h) no clinical justification, and (i) error in communication/record keeping. Six patients with 7 emergency department (ED) visits and 4 inpatient admissions, totaling 24 hospital days, were temporally associated with delays in delivery of equipment over 30 days.Conclusion: One half of commonly used DMEs were delivered within the first week. One quarter of more expensive required more steps for approval. Twenty-nine ED/hospital days with respiratory morbidities were temporally associated with delays.
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Al-shomrani, Saleh, and Paul Wang. "DMAS." ACM Communications in Computer Algebra 42, no. 1-2 (July 25, 2008): 67–68. http://dx.doi.org/10.1145/1394042.1394076.

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45

Giebel, Arthur W. "DMEK." International Ophthalmology Clinics 53, no. 1 (2013): 1–14. http://dx.doi.org/10.1097/iio.0b013e31827744c4.

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46

Arnalich-Montiel, Francisco, Ane Pérez-Sarriegui, and Alfonso Casado. "Impact of Introducing 2 Simple Technique Modifications on the Descemet Membrane Endothelial Keratoplasty Learning Curve." European Journal of Ophthalmology 27, no. 1 (May 13, 2016): 16–20. http://dx.doi.org/10.5301/ejo.5000808.

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Purpose To analyze the impact of performing premarking of the Descemet roll and using SF6 20% on a surgeon's Descemet membrane endothelial keratoplasty (DMEK) learning process. Methods A total of 30 consecutive eyes with endothelial dysfunction undergoing DMEK during the learning curve of a surgeon were retrospectively analyzed. Prior to the study, the surgeon had already performed 10 DMEKs. The first 15 consecutive patients were included in group 1 (no premarking and air tamponade) and the other 15 consecutive patients were included in group 2 (premarking and SF6 tamponade). Main outcome parameters were best-corrected visual acuity (BCVA), endothelial cell density (ECD) loss at 6 months, and intraoperative and postoperative complications. Results Among the 2 groups, BCVA and ECD loss at 6 months were similar. However, there was a statistically significant reduction in primary graft failure (40% vs 0%) and need of rebubbling due to complete or partial graft detachment (40% vs 6%) when comparing group 1 versus group 2. In group 1, half of the patients needing rebubbling had primary graft failure. Conclusions Based on our personal experience, premarking the graft to assess orientation and using a SF6 gas tamponade dramatically reduces the risk of primary graft failure and the need for rebubbling even during the first stages of the learning curve. These findings should encourage surgeons to safely change from Descemet stripping automated endothelial keratoplasty to DMEK.
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Kikuchi, Koichi, Keizo Murata, Yoshiaki Honda, Takahisa Namiki, Kazuya Saito, Hiroyuki Anzai, Keiji Kobayashi, Takehiko Ishiguro, and Isao Ikemoto. "Superconductivity in (DMET)2AuCl2and (DMET)2AuI2." Journal of the Physical Society of Japan 56, no. 12 (December 15, 1987): 4241–44. http://dx.doi.org/10.1143/jpsj.56.4241.

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48

Adeli, Fahimeh, Ebrahim Zabihi, Zeinab Abedian, Samane Gharekhani, Mahdi Pouramir, Soraya Khafri, and Maryam Ghasempour. "Comparative in vitro study of the effectiveness of Green tea extract and common storage media on periodontal ligament fibroblast viability." European Journal of Dentistry 10, no. 03 (July 2016): 408–12. http://dx.doi.org/10.4103/1305-7456.184158.

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ABSTRACT Objective: Green tea extract (GTE) was shown to be effective in preserving periodontal ligament fibroblasts (PDLFs) of avulsed teeth. This study aimed at determining the potential of GTE in preserving the viability of PDLFs comparing with different storage media. Materials and Methods: Periodontal ligament cells were obtained from freshly extracted healthy impacted third molars and cultured in Dulbecco's Modified Eagle Medium (DMEM). Cell viability was determined by storing the cells in seven media; DMEM, tap water, Hank's balanced salt solution (HBSS), whole milk, hypotonic sucrose solution, GTE, and GTE + sucrose for 1, 2, 4, and 24 h at 37°C using tetrazolium salt-based colorimetric (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. Statistical analysis was performed by one-way analysis of variance and post hoc tests. Results: GTE showed significantly higher protective effect than HBSS at 2, 4, and 24 h (P = 0.009, P = 0.02, P = 0.016), DMED at 2 h (P = 0.003), and milk at 4 h (P = 0.039). Conclusion: Although with undesirable osmolality and pH, GTE had a good ability in preserving the PDLFs comparing with other studied media.
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Perez, AlfonsoVasquez, Mehran Zarei-Ghanavati, and Christopher Liu. "DMEK calling." Journal of Ophthalmic and Vision Research 11, no. 4 (2016): 343. http://dx.doi.org/10.4103/2008-322x.194067.

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50

Gorovoy, Mark S. "DMEK Complications." Cornea 33, no. 1 (January 2014): 101–4. http://dx.doi.org/10.1097/ico.0000000000000023.

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