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1.
《Drug testing and analysis》2017,9(5):778-787
This article reports on the analytical properties of five pyrrolidinyl substituted cathinones: α ‐pyrrolidinononaphenone (α ‐PNP, 1 ), 4‐chloro‐α ‐pyrrolidinopropiophenone (4‐Cl‐α ‐PPP, 2 ), 4‐chloro‐α ‐pyrrolidinovalerophenone (4‐Cl‐α ‐PVP, 3 ), 5‐dihydrobenzofuranpyrovalerone (5‐DBFPV, 4 ), and 2‐(pyrrolidin‐1‐yl)‐1‐(5,6,7,8‐tetrahydronaphthalen‐2‐yl)hexan‐1‐one (β ‐THNPH, 5 ). These identifications were based on liquid chromatography–quadrupole time‐of‐flight‐mass spectrometry (LC–QTOF–MS), gas chromatography–mass spectrometry (GC–MS) and nuclear magnetic resonance spectroscopy (NMR). To our knowledge, no analytical data about α ‐PNP, 4‐Cl‐α ‐PPP, 4‐Cl‐α ‐PVP, and β ‐THNPH have appeared until now, making this the first report on these compounds. Moreover, in order to study the collision‐induced dissociation (CID) characteristic fragmentation routes of pyrrolidinyl substituted cathinones, a total number of 13 pyrrolidinyl substituted cathinones were selected and discussed. The major fragmentation pathways under CID mode are produced, leading to the formation of characteristic ions. Product ions of [M‐C4H9N]+ and CnH2nN+ indicate the presence of pyrrolidinyl substitution. Characteristic fragments are also produced via the cleavages of the CH–N(CH2)4 bond and the CO‐CHN bond. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
2.
Franca Franchi Eugenia Biguzzi Ida Martinelli Paolo Bucciarelli Claudia Palmucci Simona D’Agostino Flora Peyvandi 《Thrombosis research》2013
Introduction
Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, age, menopause and hormone therapy on natural anticoagulant plasma levels in a large group of healthy individuals, and to evaluate the need of separate reference ranges.Materials and Methods
AT and PC were measured with a chromogenic assay, antigenic free PS with an ELISA test. To evaluate the effect of sex, age, oral contraception, hormonal status (and their interaction) on AT, PC and PS levels, linear regression models were used. Biological relevance and the value of the normal deviate z were chosen as rules to decide for separate reference ranges.Results
The study population consisted of 1837 healthy adult individuals (741 men, 1096 women), aged 18-85 years (median age: 44 years). In men AT levels decreased after the age of 50 years. Men had higher levels of PS than women, particularly at young ages. In women, after correction for menopause, only PC levels increased with age. Menopause affected AT and PS, but not PC levels. Oral contraceptive intake was associated with a decrease of AT and PS, and an increase of PC levels.Conclusions
For AT, PC and PS, sex- and age-specific normal reference ranges can be useful, in order to better discriminate true carriers of a natural anticoagulant deficiency. 相似文献3.
Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH. 相似文献
4.
Olga Kotsovolou Magnus Ingelman-Sundberg Matti A. Lang Marios Marselos David H. Overstreet Zoi Papadopoulou-Daifoti Inger Johanson Andrew Fotopoulos Maria Konstandi 《Progress in neuro-psychopharmacology & biological psychiatry》2010
The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague–Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16α-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(α)pyrene (B(α)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(α)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity. 相似文献
5.
Selective impairment of drug-metabolizing enzymes in pig liver during subchronic dietary exposure to aflatoxin B1. 总被引:1,自引:0,他引:1
Guylaine M Meissonnier Joelle Laffitte Nicolas Loiseau Etienne Benoit Isabelle Raymond Philippe Pinton Anne-Marie Cossalter Gérard Bertin Isabelle P Oswald Pierre Galtier 《Food and chemical toxicology》2007,45(11):2145-2154
Consequences of subchronic exposure to aflatoxin B1 (AFB1) on liver monooxygenase and transferase enzymes were compared in control pigs and pigs given 385, 867 or 1,807 microg AFB1/kg of feed for 4 weeks. Animals exposed to the highest dose of toxin developed clinical signs of aflatoxicosis, like liver fibrosis, hepatic dysfunction and decreased weight gain. This group had significantly lower levels of liver cytochrome P450, ethoxyresorufin O-deethylase (EROD) activity, testosterone metabolism, P450 1A and P450 3A protein expression. By comparison, mild degenerative hepatic changes, no hepatic dysfunction but a similar pattern of liver P450 enzymes activity without changes in P450 3A expression were observed in pigs exposed to 867 microg AFB1/kg of feed. Benzphetamine and aminopyrine N-demethylase activities were increased in pigs exposed to 867 or 1,807microg AFB1/kg of feed. Pigs exposed to 385 microg AFB1/kg of feed had low levels of EROD activity and all other biotransformation and clinical parameters remained at control levels. Aniline hydroxylase activity, P450 2C protein expression, UDP-glucuronosyl and glutathione S-transferase activities were unaffected at all doses of AFB1. In conclusion, P450 1A and P450 3A appear to be specific targets of AFB1 even if pig did not display clinical sign of liver toxicosis. 相似文献
6.
Chen G 《Biochemical pharmacology》2004,67(7):1355-1361
Sulfotransferases are phase II drug-metabolizing enzymes that catalyze the sulfation of hydroxyl-containing compounds, leading to detoxification of xenobiotic toxicants. The universal sulfuryl donor is adenosine 3'-phosphate-5'-phosphosulfate. Human simple phenol sulfotransferase (P-PST) is one of the major human sulfotransferases that catalyze the sulfation of most phenols. Human monoamine phenol sulfotransferase (M-PST) has high affinity for monoamines and also catalyzes the sulfation of simple phenols at high substrate concentrations. In this report, the amino acid modification method was used for studies of His residues in the active site of P-PST and M-PST. The His specific modification reagent diethylpyrocarbonate was used for the modification of His residues in P-PST and M-PST. Diethylpyrocarbonate inactivation kinetic data suggest that there is one His residue in the active site that is critical for catalytic activity of both P-PST and M-PST. The modification has no effect on phenol or monoamine substrate binding for M-PST, but it does have an effect on adenosine 3'-phosphate-5'-phosphosulfate binding with M-PST. The experimental results agree with amino acid sequence alignment, mutation, and the crystal structures of P-PST and M-PST and suggest that His108 is the only critical His residue in both P-PST and M-PST. The differing roles His108 plays in P-PST and M-PST may explain the substrate specificity of the two isoforms. 相似文献
7.
B. B. Anderson J. E. Clements G. M. Perry C. Studds C. Vullo G. Salsini 《European journal of haematology》1987,38(1):12-20
Per cent stimulation of GR activity by FAD in vitro and PNP oxidase activity were measured in G6PD deficiency, heterozygous β-thalassaemia and controls. It is confirmed that, in contrast to the high stimulation of GR by FAD commonly found in thalassaemia indicating red-cell deficiency of FAD, and shown here to be greater in the Italian subjects, GR is usually saturated with FAD in G6PD deficiency, leading to high in vitro activity. Unexpectedly, on the other hand, low FMN-dependent PNP oxidase activity due to red-cell deficiency of FMN, confirmed by response to oral riboflavin, was found in the majority of subjects with G6PD deficiency, similar to that found in heterozygous β-thalassaemia. Whereas this is explained in thalassaemia by an inherited slow red-cell metabolism of riboflavin to FMN, it is suggested that in G6PD deficiency an increased rate of red-cell metabolism of FMN to FAD leads to the low FMN and high FAD. When G6PD deficiency occurs with heterozygous β-thalassaemia, GR is usually saturated with FAD as in G6PD deficiency alone, unless there is an inherited, very slow red-cell metabolism of riboflavin to FMN. The part played by GR in haemolytic crises in G6PD deficiency is discussed. 相似文献
8.
Anupam Mathur Madhava B. Mallia Haladhar D. Sarma Sharmila Banerjee Meera Venkatesh 《Journal of labelled compounds & radiopharmaceuticals》2011,54(3):150-156
123I‐labeled fatty acids and 18F‐FDG are used as metabolic markers for detecting myocardial abnormalities. However, a 99mTc‐based molecule may find wider application. In the present work, a new 99mTc‐labeled, uni‐positively charged, 16‐carbon fatty acid has been prepared and evaluated in normal Swiss mice. The results are then compared with the neutral analogue reported earlier. A 16‐cysteinyl hexadecanoic acid conjugate was synthesized in a six‐step synthetic procedure starting with 16‐bromohexadecanoic acid. The ligand upon incubation with [99mTcN(PNP6)]2+ core formed the required positively charged complex in ~85% yield. The complex, which was obtained as a mixture of syn‐anti isomers, was purified by HPLC and the major fraction was used for in vivo studies in Swiss mice. The biodistribution studies in Swiss mice showed initial uptake similar to 125I‐IPPA followed by rapid clearance from the myocardium till 10 min p.i. Thereafter, the rate of clearance was significantly decreased, an observation reported earlier for positively charged fatty acid complexes. In terms of absolute uptake, the positively charged complex performed better than the neutral analogue reported earlier. The positively charged fatty acid complexes, prepared using [99mTcN(PNP)]2+ core, seems to be better candidates for the development of myocardial metabolic tracers than their neutral counterparts. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
9.
目的分析PNP—TK融合自杀基因系统及PNP单自杀基因系统对肝癌细胞的杀伤作用及二者对肝癌细胞潜在的杀伤机制。方法构建融合基因表达我体pcDNA3.0/PNP—TK。经酶切、PCR及测序鉴定重组体。G418筛选获得稳定转染了pcDNA3.0/PNP-TK的HepG2细胞克隆。RT—PCR和Western Blotting检测融合基因在HepG2细胞中的表达。台盼兰排斥法检测细胞的生长曲线,MTT法检测细胞对相应前药的敏感性及分别在一种和两种前药作用下所导致的旁观者效应。结果融合基因片段PNP—TK正确插入了pcDNA3.0载体中,pcDNA3.0,PNP-TK在肝癌细胞株HepG2中实现了表达。抗性细胞克隆对相应的前药十分敏感。在两种前药的联合作用下。pcDNA3.0/PNP-TK所导致的旁观者效应明显强于只给予MeP-dR一种前药以及pcDNA3.0/PNP单基因系统所致的旁观者效应。结论具有双自杀基因功能的表达载体pcDNA3.0/PNP-TK对肝癌细胞的杀伤效果优于PNP单自杀基因系统。 相似文献
10.
Yang X Jin T Press R Quezada HC Fredrikson S Zhu J 《Journal of neuroimmunology》2008,200(1-2):129-132
The proportion of peripheral blood mononuclear cells (PBMCs) expressing TNF-alpha and its receptors (TNFR1, TNFR2) and the serum concentrations of its soluble forms were analyzed by FACS and ELISA in the patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and in controls. Elevated levels of TNFR2 were observed on blood T cells in CIDP and idiopathic polyneuropathy. Low levels of TNFR1 were detected on monocytes in the subgroup of patients with CIDP examined after treatment with intravenous immunoglobulin. However, the proliferative activity of PBMCs in CIDP was not influenced by soluble recombinant TNFR1. Our limited data suggested the exact role of TNF-alpha and its receptors need to study further in CIDP, as well as in idiopathic neuropathies. 相似文献