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Sample records for antipyrine

  1. Antipyrine-Benzocaine Otic

    Science.gov (United States)

    Antipyrine and benzocaine otic is used to relieve ear pain and swelling caused by middle ear infections. It may be used ... of ear wax in the ear. Antipyrine and benzocaine are in a class of medications called analgesics. ...

  2. Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders.

    Directory of Open Access Journals (Sweden)

    Nayak V

    1991-01-01

    Full Text Available Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.

  3. Lung water measurements with iodo-antipyrine

    Energy Technology Data Exchange (ETDEWEB)

    Chu, R.Y.L.; Carlile, P.V. Jr.; Gray, B.A.; Allen, E.W.; Basmadjian, G.; Myers, J.

    1988-11-01

    /sup 131/I labeled iodo-antipyrine and /sup 99m/Tc labeled erythrocytes were used to measure water content in lungs. These radioactive tracers were injected into 10 rabbits with normal lungs and 11 rabbits with injured lungs. Blood samples were drawn and the subjects were killed. The lungs were removed, weighed and homogenized. Samples of blood and lung homogenate were assayed for /sup 131/I and /sup 99m/Tc. Samples were also weighed before and after drying to a constant weight at 70-75/sup 0/C. Extravascular lung water was determined by the dual isotope technique and again by gravimetric analysis. The average ratio of the results from the 2 different methods is 1.03+-0.15. The 2 methods were compared by regression analysis and the correlation coefficient was 0.92+-0.09. Our investigation suggests the possibility of measurement of lung water with equilibrium distribution of iodo-antipyrine.

  4. Antipyrine clearance during experimental and occupational exposure to toluene

    DEFF Research Database (Denmark)

    Døssing, M; Bælum, Jesper; Lundqvist, G R

    1983-01-01

    into four groups. Eighteen printers and 21 controls were exposed to 100 ppm of toluene during 6.5 hours in an exposure chamber. The remaining 18 printers and 18 controls were exposed to 0 ppm of toluene under similar conditions. The salivary clearance of antipyrine was measured immediately after the stay...... in the exposure chamber to investigate a possible acute change in liver function and was repeated two weeks later, shortly before the summer vacation. Antipyrine clearance was measured again at the end of the summer vacation-four weeks after exposure. To study a possible effect of chronic exposure on antipyrine...... clearance 12 printing trade workers with 17 years (median) of occupational exposure to toluene vapour at concentrations of about 100 ppm were investigated before and four weeks after cessation of exposure. No difference in antipyrine clearance was found either within the groups or between the groups at any...

  5. Simple spectrophotometric methods for the simultaneous determination of antipyrine and benzocaine

    Directory of Open Access Journals (Sweden)

    Hanan A. Merey

    2016-12-01

    Full Text Available Antipyrine and benzocaine are formulated together for the treatment of ear inflammation and to relieve pain. Four spectrophotometric methods were developed for the simultaneous determination of antipyrine (AN and benzocaine (BE in their combined dosage form. Method A depends on applying dual wavelength method where antipyrine was determined by measuring the absorbance at 254.1 and 309.1 nm (corresponding to zero difference of benzocaine, while the absorbance difference at 230.1 and 263.5 nm (corresponding to zero difference of antipyrine was selected for benzocaine determination in the laboratory prepared spectrum. Method B depends on measuring the peak amplitude of first derivative at 305 nm for calculating benzocaine concentration then the total concentration of both drugs was determined using isoabsorptive point at 257.4 nm (antipyrine concentration was then calculated by subtraction. Method C is based on measuring the peak difference of the ratio spectra at Δp (239.1–285 nm and Δp (301.4–250 nm for the determination of antipyrine and benzocaine, respectively. Method D depends on measuring peak to peak amplitude of the first derivative of ratio spectra at (234.5 + 244.2 nm and peak amplitude at 295.5 nm for the determination of antipyrine and benzocaine, respectively. The proposed methods were validated and applied for the analysis of antipyrine and benzocaine in their laboratory prepared mixtures and pharmaceutical formulation. Statistical comparison between the results of the proposed methods and those of the reported methods showed no significant difference.

  6. Albendazole metabolism in patients with neurocysticercosis: antipyrine as a multifunctional marker drug of cytochrome P450

    Directory of Open Access Journals (Sweden)

    M.P. Marques

    2002-02-01

    Full Text Available The present study investigates the isoform(s of cytochrome P450 (CYP involved in the metabolism of albendazole sulfoxide (ASOX to albendazole sulfone (ASON in patients with neurocysticercosis using antipyrine as a multifunctional marker drug. The study was conducted on 11 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h. On the 5th day of albendazole treatment, 500 mg antipyrine was administered po. Blood and urine samples were collected up to 72 h after antipyrine administration. Plasma concentrations of (+-ASOX, (--ASOX and ASON were determined by HPLC using a chiral phase column and detection by fluorescence. The apparent clearance (CL/f of ASON and of the (+ and (--ASOX enantiomers were calculated and compared to total antipyrine clearance (CL T and the clearance for the production of the three major antipyrine metabolites (CLm. A correlation (P<=0.05 was obtained only between the CL T of antipyrine and the CL/f of ASON (r = 0.67. The existence of a correlation suggests the involvement of CYP isoforms common to the metabolism of antipyrine and of ASOX to ASON. Since the CL T of antipyrine is a general measure of CYP enzymes but with a slight to moderate weight toward CYP1A2, we suggest the involvement of this enzyme in ASOX to ASON metabolism in man. The study supports the establishment of a specific marker drug of CYP1A2 in the study of the in vivo metabolism of ASOX to ASON.

  7. Liver volume, portal vein flow, and clearance of indocyanine green and antipyrine in hyperthyroidism before and after antithyroid treatment

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Sonne, J; Court-Payen, M

    1999-01-01

    The aim of the study was to examine liver volume, portal vein flow, and indocyanine green (ICG) and antipyrine clearance in hyperthyroidism before and after antithyroid drug treatment.......The aim of the study was to examine liver volume, portal vein flow, and indocyanine green (ICG) and antipyrine clearance in hyperthyroidism before and after antithyroid drug treatment....

  8. Antipyrine, oxazepam, and indocyanine green clearance in patients with chronic pancreatitis and healthy subjects

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Sonne, J; Larsen, S

    1999-01-01

    Hepatic drug metabolism was examined in patients with chronic pancreatitis and healthy controls by using a cocktail design with three different model compounds: antipyrine to express phase-I oxidation, oxazepam to express phase-II conjugation, and indocyanine green (ICG), a high-clearance compound....

  9. Antipyrine-gamma cyclodextrin inclusion complex: Molecular modeling, preparation, characterization and cytotoxicity studies

    Science.gov (United States)

    Gannimani, Ramesh; Perumal, Amanda; Ramesh, Muthusamy; Pillay, Karen; Soliman, Mahmoud E.; Govender, Patrick

    2015-06-01

    Molecular docking, semi-empirical and molecular dynamics studies were conducted for α, β and γ-cyclodextrin-associated inclusion complexes of antipyrine. The results of molecular modeling were systematically analyzed to determine the stability of inclusion complexes. In preliminary computational screening, β and γ-cyclodextrin inclusion complexes of antipyrine were found to be more stable as compared to α-cyclodextrin based on docking score and binding free energies. Further, inclusion complex of antipyrine with γ-cyclodextrin was prepared by freeze drying method. Formation of the inclusion complex was investigated by solid state characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. The changes observed in decomposition temperature, diffractogram, vibrational frequencies and morphological appearance confirmed the formation of inclusion complex. In addition, results from 1H NMR and 2D NOESY studies supported the inclusion phenomenon. The results obtained from computational studies were found to be in consistent with experimental data to ascertain the encapsulation of antipyrine into γ-cyclodextrin. The inclusion complex was found to be non-toxic toward MDCK-1 cell lines. Thus, this approach may be helpful in the formulation of drug molecules using cyclodextrins.

  10. Transplacental transfer of acrylamide and glycidamide are comparable to that of antipyrine in perfused human placenta.

    Science.gov (United States)

    Annola, Kirsi; Karttunen, Vesa; Keski-Rahkonen, Pekka; Myllynen, Päivi; Segerbäck, Dan; Heinonen, Seppo; Vähäkangas, Kirsi

    2008-11-10

    Most drugs can penetrate the placenta but there are only a few studies on placental transfer of environmental toxic compounds. In this study, we used dual recirculating human placental perfusion to determine the transfer rate through the placenta of a neurotoxic and carcinogenic compound found in food, acrylamide and its genotoxic metabolite glycidamide. Putative acrylamide metabolism into glycidamide during the 4-h perfusions and acrylamide-derived DNA adducts in placental DNA after perfusions were also analyzed. Placentas were collected immediately after delivery and kept physiologically functional as confirmed by antipyrine kinetics, glucose consumption and leak from fetal to maternal circulation. Acrylamide (5 or 10 microg/ml) or glycidamide (5 microg/ml), both with antipyrine (100 microg/ml), was added to maternal circulation. Acrylamide and glycidamide were analyzed in the perfusion medium by liquid chromatography/mass spectrometry. Acrylamide and glycidamide crossed the placenta from maternal to fetal circulation with similar kinetics to antipyrine, suggesting fetal exposure if the mother is exposed. The concentrations in maternal and fetal circulations equilibrated within 2h for both studied compounds and with both concentrations. Acrylamide metabolism into glycidamide was not detected during the 4-h perfusions. Moreover, DNA adducts were undetectable in the placentas after perfusions. However, fetuses may be exposed to glycidamide after maternal metabolism. Although not found in placental tissue after 4h of perfusion, it is possible that glycidamide adducts are formed in fetal DNA.

  11. Antipyrine removal by TiO2 photocatalysis based on spinning disc reactor technology.

    Science.gov (United States)

    Expósito, A J; Patterson, D A; Mansor, W S W; Monteagudo, J M; Emanuelsson, E; Sanmartín, I; Durán, A

    2017-02-01

    The photo-degradation of the emerging contaminant antipyrine (AP) was studied and optimized in a novel photocatalytic spinning disc reactor (SDR). A heterogeneous process (UV/H2O2/TiO2) was used. TiO2 was immobilized on the surface of a glass disc using a sol-gel method. A factorial design of experiments followed by a Neural Networks fitting allowed the optimal conditions to be determined for treating 50 mg/L of AP. Under these conditions (pH = 4; [H2O2]0 = 1500 mg/L; disc speed = 500 rpm; flowrate = 25 mL/s), AP was completely degraded in 120 min and regeneration of the disc allowed 10 cycles with no loss in efficiency. The value of the apparent volumetric rate constant was found to be 6.9·10(-4) s(-1) with no apparent mass transfer limitation. Based on the main intermediates identified, a mechanism is proposed for antipyrine photodegradation: Firstly, cleavage of the NN bond of penta-heterocycle leads to the formation of two aromatic acids and N-phenylpropanamide. An attack to the CN bond in the latter compound produces benzenamine. Finally, the phenyl ring of the aromatic intermediates are opened and molecular organic acids are formed.

  12. Degradation of antipyrine by UV, UV/H₂O₂ and UV/PS.

    Science.gov (United States)

    Tan, Chaoqun; Gao, Naiyun; Deng, Yang; Zhang, Yongji; Sui, Minghao; Deng, Jing; Zhou, Shiqing

    2013-09-15

    Degradation of antipyrine (AP) in water by three UV-based photolysis processes (i.e., direct UV, UV/H₂O₂, UV/persulfate (UV/PS)) was studied. For all the oxidation processes, the AP decomposition exhibited a pseudo-first-order kinetics pattern. Generally, UV/H₂O₂ and UV/PS significantly improved the degradation rate relevant to UV treatment alone. The pseudo-first-order degradation rate constants (kobs) were, to different degrees, affected by initial AP concentration, oxidant dose, pH, UV irradiation intensity, and co-existing chemicals such as humic acid, chloride, bicarbonate, carbonate and nitrate. The three oxidation processes followed the order in terms of treatment costs: UV/PS>UV>UV/H₂O₂ if the energy and chemical costs are considered. Finally, the AP degradation pathways in the UV/H₂O₂ and UV/PS processes are proposed. Results demonstrated that UV/H₂O₂ and UV/PS are potential alternatives to control water pollution caused by emerging contaminants such as AP.

  13. Electrical conductivity and dielectric relaxation of 2-(antipyrin-4-ylhydrazono)-2-(4-nitrophenyl)acetonitrile

    Energy Technology Data Exchange (ETDEWEB)

    El-Menyawy, E.M., E-mail: emad_elmenyawy@yahoo.com [Solid State Electronics Laboratory, Solid State Physics Department, Physics Division, National Research Center, Dokki, Cairo 12311 (Egypt); Zedan, I.T. [Basic Science Department, High Institute of Engineering and Technology, El-Arish, North Sinai (Egypt); Nawar, H.H. [Department of Chemistry, Faculty of Education, Al Jabal Al Gharbi University (Libya)

    2014-03-15

    The electrical and dielectric properties of the synthesized 2-(antipyrin-4-ylhydrazono)-2-(4-nitrophenyl)acetonitrile (AHNA) have been studied. The direct and alternating current (DC and AC) conductivities and complex dielectric constant were investigated in temperature range 303–403 K. The AC conductivity and dielectric properties of AHNA were investigated over frequency range 100 Hz–5 MHz. From DC and AC measurements, electrical conduction is found to be a thermally activated process. The frequency-dependent AC conductivity obeys Jonscher's universal power law in which the frequency exponent decreases with increasing temperature. The correlated barrier hopping (CBH) is the predominant model for describing the charge carrier transport in which the electrical parameters are evaluated. The activation energy is found to decrease with increasing frequency. The behaviors of dielectric and dielectric loss are discussed in terms of a polarization mechanism. The dielectric loss shows frequency power law from which the maximum barrier height is determined as 0.19 eV in terms of the Guintini model.

  14. Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    La Delfa, I.; Zhu, Q.M.; Mo, Z.; Blaschke, T.F.

    1989-01-01

    Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The (/sup 14/C)antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73% +/- 2%), demethylase (mean = -90% +/- 2%), and nondemethylase (mean = -60% +/- 4%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as /sup 14/CO/sub 2/ was decreased by 50-80% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.

  15. Influencing factors and degradation products of antipyrine chlorination in water with free chlorine

    Institute of Scientific and Technical Information of China (English)

    Meiquan Cai; Liqiu Zhang; Fei Qi; Li Feng

    2013-01-01

    Owing to its low cost,free chlorine is one of the most common disinfectants for wastewater and drinking water treatment.However,the formation of disinfection byproducts has been found to occur after free chlorine disinfection in recent decades.Antipyrine (ANT),an anti-inflammatory analgesic,has been frequently detected in the aquatic environment.In this work.the removal efficiency of ANT by free chlorine oxidation in ultrapure water was investigated with batch experiments.The influencing factors on the removal of ANT were explored at initial concentrations of ANT from 0.04 to 0.64 mg/L,free chlorine dosage from 0.30 to 1.31 mg/L,and pH from 1.5 to 9.0.The main degradation products were identified by solid phase extraction-gas chromatography-mass spectrometry.The results showed that ANT reacted rapidly with free chlorine in ultrapure water systems and up to 90.6% removal efficiency of ANT was achieved after 25 sec (initial free chlorine 1 mg/L,ANT 0.5 mg/L,pH 7.0).Higher oxidant dosage,lower ANT initial concentration and low pH favor the ANT removal.The main degradation product in ANT chlorination was a monochlorine substitution product (4-chloro-l,2-dihydro1,5-dimethyl-2-phenyl-3H-pyrazol-3-one),which can be further chlorinated by free chlorine.In addition,the total organic carbon result indicated that ANT is difficult to be mineralized using chlorine.

  16. Influencing factors and degradation products of antipyrine chlorination in water with free chlorine.

    Science.gov (United States)

    Cai, Meiquan; Zhang, Liqiu; Qi, Fei; Feng, Li

    2013-01-01

    Owing to its low cost, free chlorine is one of the most common disinfectants for wastewater and drinking water treatment. However, the formation of disinfection byproducts has been found to occur after free chlorine disinfection in recent decades. Antipyrine (ANT), an anti-inflammatory analgesic, has been frequently detected in the aquatic environment. In this work, the removal efficiency of ANT by free chlorine oxidation in ultrapure water was investigated with batch experiments. The influencing factors on the removal of ANT were explored at initial concentrations of ANT from 0.04 to 0.64 mg/L, free chlorine dosage from 0.30 to 1.31 mg/L, and pH from 1.5 to 9.0. The main degradation products were identified by solid phase extraction-gas chromatography-mass spectrometry. The results showed that ANT reacted rapidly with free chlorine in ultrapure water systems and up to 90.6% removal efficiency of ANT was achieved after 25 sec (initial free chlorine 1 mg/L, ANT 0.5 mg/L, pH 7.0). Higher oxidant dosage, lower ANT initial concentration and low pH favor the ANT removal. The main degradation product in ANT chlorination was a monochlorine substitution product (4-chloro-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one), which can be further chlorinated by free chlorine. In addition, the total organic carbon result indicated that ANT is difficult to be mineralized using chlorine.

  17. Circulatory transport and capillary-tissue exchange as determinants of the distribution kinetics of inulin and antipyrine in dog.

    Science.gov (United States)

    Weiss, Michael; Krejcie, Tom C; Avram, Michael J

    2007-04-01

    A pharmacokinetic model was developed to estimate physiologically meaningful parameters of distribution kinetics from plasma concentration-time data. The model is based on simultaneously measured disposition curves of drug and vascular marker. Employing residence time distribution theory, a recirculatory model with two subsystems, the pulmonary and systemic circulation, was constructed. In addition to intravascular mixing, the axially distributed model of the systemic circulation accounts for transcapillary transport of solutes, quantified by permeability-surface area product (PS) and diffusional equilibration time. Parameters of ICG, inulin, and antipyrine were estimated from disposition data obtained in awake dogs under control conditions and during an isoproterenol infusion or moderate hypovolemia. Results suggest that distribution kinetics is (1) governed by extravascular diffusion and (2) its dependency on cardiac output decreases with increasing diffusional resistance. Hemorrhage decreased the effective PS of inulin. In conclusion, this novel mechanistic model effectively described both the permeability-limited distribution of inulin into interstitial fluid and the flow-limited distribution of antipyrine into total body water and might be useful for other drugs.

  18. Synthesis, Characterization and Activity of Rare Earth Complexes with Schiff Base From 2,6-Diformylpyridine N-Oxide and 4-Amino-antipyrine

    Institute of Scientific and Technical Information of China (English)

    于青; 唐瑜; 谭民裕

    2002-01-01

    Six new rare earth complexes with Schiff base from 2,6-diformylpyridine N-oxide and 4-amino-antipyrine were synthesized. These complexes with general formula REL(NO3)3 (RE=La, Pr, Eu, Tb, Er, Y) were characterized by elemental analysis, IR, UV, molar conductance measurements and antimicrobial activity.

  19. Simultaneous determination of acrylamide, its metabolite glycidamide and antipyrine in human placental perfusion fluid and placental tissue by liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Annola, Kirsi; Keski-Rahkonen, Pekka; Vähäkangas, Kirsi; Lehtonen, Marko

    2008-12-15

    A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous determination of acrylamide (AA) and its genotoxic metabolite glycidamide (GA) with a test marker antipyrine (AP) in placental tissue and perfusion medium used in human placental perfusion studies. An internal standard ((13)C-acrylamide) was added to the samples which were then deproteinized with acetonitrile. Chromatographic separation was performed on a reversed phase column with a gradient elution of acetonitrile and 0.01% formic acid at a flow rate of 0.3 mL/min. Detection and quantification of the analytes were carried out with a triple quadrupole mass spectrometer using positive electrospray ionization (ESI) and multiple reaction monitoring (MRM). The method was validated and linear over a concentration range of 0.5-20 microg/mL for acrylamide and glycidamide and 5-200 microg/mL for antipyrine. The lower limit of quantification for acrylamide and glycidamide was 0.5 microg/mL and for antipyrine 5 microg/mL. The method was selective, and good accuracy, precision, recovery, and stability were obtained for concentrations within the standard curve. The method was successfully used to analyze the placental perfusion medium and tissue samples in a toxicokinetic study for transplacental transfer of acrylamide and glycidamide. This is the first time that acrylamide, glycidamide and antipyrine are measured simultaneously.

  20. Determination of the tissue-to-blood partition coefficient for 131iodo-antipyrine in human subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Jelnes, R; Astrup, A

    1985-01-01

    131Iodo-antipyrine (131I-AP) is commonly used for blood flow measurements in adipose tissue. These estimations have been based on the assumption of the tissue-to-blood partition coefficient being 1 ml g-1. No exact determination of the tissue-to-blood partition coefficient for 131I-AP in adipose...... tissue has been carried out. In the present study a partition coefficient of 1.12 +/- 0.06 (mean +/- S.D.) for 131I-AP in adipose tissue has been determined based on the partition coefficient for 131I-AP between lipid-saline (1.24 ml g-1), red blood cells-plasma (0.64 ml g-1), protein-saline (0.19 ml g-1...

  1. Degradation of antipyrine by UV, UV/H{sub 2}O{sub 2} and UV/PS

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Chaoqun [State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai City 200092 (China); Gao, Naiyun, E-mail: gaonaiyun@126.com [State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai City 200092 (China); Deng, Yang [Department of Earth and Environmental Studies, Montclair State University, Montclair, NJ 07043 (United States); Zhang, Yongji; Sui, Minghao; Deng, Jing; Zhou, Shiqing [State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai City 200092 (China)

    2013-09-15

    Highlights: • The antipyrine decomposition exhibited a pseudo-first-order kinetics pattern well. • The k{sub obs} with irradiance or oxidant dosage presented a linear relationship well. • The k{sub obs} exhibit an exponential trend as a function of [AP]{sub 0} for three systems. • UV/H{sub 2}O{sub 2} behaved best at pH 2.5–10, while UV/PS behaved best at pH 10.0–11.5. • Cost for chemicals was firstly taken into account in calculation of the EE/O values. -- Abstract: Degradation of antipyrine (AP) in water by three UV-based photolysis processes (i.e., direct UV, UV/H{sub 2}O{sub 2}, UV/persulfate (UV/PS)) was studied. For all the oxidation processes, the AP decomposition exhibited a pseudo-first-order kinetics pattern. Generally, UV/H{sub 2}O{sub 2} and UV/PS significantly improved the degradation rate relevant to UV treatment alone. The pseudo-first-order degradation rate constants (k{sub obs}) were, to different degrees, affected by initial AP concentration, oxidant dose, pH, UV irradiation intensity, and co-existing chemicals such as humic acid, chloride, bicarbonate, carbonate and nitrate. The three oxidation processes followed the order in terms of treatment costs: UV/PS > UV > UV/H{sub 2}O{sub 2} if the energy and chemical costs are considered. Finally, the AP degradation pathways in the UV/H{sub 2}O{sub 2} and UV/PS processes are proposed. Results demonstrated that UV/H{sub 2}O{sub 2} and UV/PS are potential alternatives to control water pollution caused by emerging contaminants such as AP.

  2. The activity of mixed function oxidases, estimated by in vivo antipyrine clearance, is similar in horses and camels.

    Science.gov (United States)

    Wasfi, I A; Zorob, O M; Boni, N S; Hadi, A A; Agha, B A; Elghazali, M

    1998-02-01

    The activity of hepatic mixed function oxidases was compared in horses and camels (Camelus dromedarius) by studying the pharmacokinetics of antipyrine in seven camels and five horses following intravenous administration of a single dose of antipyrine (25 mg/kg). The data obtained (mean +/- SEM and median in brackets) in camels and horses, respectively, were as follows: the elimination half-lives were 3.25 +/- 0.23 (3.19) and 3.09 +/- 0.25 (2.90) hr; the apparent volumes of distribution (area method) were 0.691 +/- 0.045 (0.648) and 0.642 +/- 0.034 (0.676) l/kg; the volumes of distribution at steady state were 0.659 +/- 0.040 (0.607) and 0.620 +/- 0.030 (0.653) l/kg; the volume of the central compartment of the two-compartment pharmacokinetic model were 0.386 +/- 0.0523 (0.349) and 0.298 +/- 0.05 (0.308) l/kg; total body clearances were 0.148 +/- 0.008 (0.158) and 0.145 +/- 0.007 (0.147) l/kg/hr; the areas under the curves to infinity were 171.0 +/- 9 (165) and 175 +/- 8.0 (170) micrograms.ml.hr. There was no statistical significance in any parameter between camels and horses which suggests that the activity of hepatic mixed function oxidases is similar in horses and camels.

  3. [Quantification of the drug-metabolizing enzyme system in liver diseases: a comparison between antipyrine saliva clearance and the aminopyrine breath test].

    Science.gov (United States)

    von Mandach, U; Jost, G; Preisig, R

    1985-05-11

    The metabolic activity of the hepatic cytochrome P450 system was studied in 53 ambulatory subjects. 18 of these were cirrhotics and 23 had non-cirrhotic liver disease, documented by biopsy, serologic, ultrasound or computerized tomography findings, and characterized by quantitative liver function tests, such as galactose elimination capacity and indocyanine green fractional clearance. For comparison, 12 normal control subjects were also included. All subjects were given 10 mg/kg body weight antipyrine and saliva concentrations determined with an HPLC-method at 24 and 48 hours after dosing. Antipyrine saliva clearance (ASC) was calculated according to a two-point method (Cl1), and compared with a one-point method (Cl2) using the 24 h sample only. These subjects also underwent an aminopyrine breath test (ABT), breath samples being collected at regular intervals during 60 minutes following injection of a tracer dose of 1.5 muCi (14C-dimethylamino)antipyrine. Cl1 and Cl2 correlated strongly (r = 0.93). On the basis of smaller variations (particularly in control subjects), better definition of disease severity and convenience and time saving, Cl2 is to be preferred. Comparison of Cl2 with ABT showed that both procedures apparently quantify overlapping enzymatic activities. However, the relationship between Cl2 and ABT values, albeit highly significant (r = 0.72), suggests that only about half of the variables are subject to the same determinant. In addition, a positive intercept of the regression line extrapolated to the Cl2 axis points to quantitatively important extrahepatic breakdown of antipyrine. The results suggest that, in view of the wide variation in normal values (presumably in part influenced by exogenous pollutants), ASC only provides an approximation of hepatic metabolic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. A fully automated effervescence assisted dispersive liquid-liquid microextraction based on a stepwise injection system. Determination of antipyrine in saliva samples.

    Science.gov (United States)

    Medinskaia, Kseniia; Vakh, Christina; Aseeva, Darina; Andruch, Vasil; Moskvin, Leonid; Bulatov, Andrey

    2016-01-01

    A first attempt to automate the effervescence assisted dispersive liquid-liquid microextraction (EA-DLLME) has been reported. The method is based on the aspiration of a sample and all required aqueous reagents into the stepwise injection analysis (SWIA) manifold, followed by simultaneous counterflow injection of the extraction solvent (dichloromethane), the mixture of the effervescence agent (0.5 mol L(-1) Na2CO3) and the proton donor solution (1 mol L(-1) CH3COOH). Formation of carbon dioxide microbubbles generated in situ leads to the dispersion of the extraction solvent in the whole aqueous sample and extraction of the analyte into organic phase. Unlike the conventional DLLME, in the case of EA-DLLME, the addition of dispersive solvent, as well as, time consuming centrifugation step for disruption of the cloudy state is avoided. The phase separation was achieved by gentle bubbling of nitrogen stream (2 mL min(-1) during 2 min). The performance of the suggested approach is demonstrated by determination of antipyrine in saliva samples. The procedure is based on the derivatization of antipyrine by nitrite-ion followed by EA-DLLME of 4-nitrosoantipyrine and subsequent UV-Vis detection using SWIA manifold. The absorbance of the yellow-colored extract at the wavelength of 345 nm obeys Beer's law in the range of 1.5-100 µmol L(-1) of antipyrine in saliva. The LOD, calculated from a blank test based on 3σ, was 0.5 µmol L(-1).

  5. A fully automated effervescence assisted dispersive liquid–liquid microextraction based on a stepwise injection system. Determination of antipyrine in saliva samples

    Energy Technology Data Exchange (ETDEWEB)

    Medinskaia, Kseniia; Vakh, Christina; Aseeva, Darina [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation); Andruch, Vasil, E-mail: vasil.andruch@upjs.sk [Department of Analytical Chemistry, University of P.J. Šafárik, SK-04154 Košice (Slovakia); Moskvin, Leonid [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation); Bulatov, Andrey, E-mail: bulatov_andrey@mail.ru [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation)

    2016-01-01

    A first attempt to automate the effervescence assisted dispersive liquid–liquid microextraction (EA-DLLME) has been reported. The method is based on the aspiration of a sample and all required aqueous reagents into the stepwise injection analysis (SWIA) manifold, followed by simultaneous counterflow injection of the extraction solvent (dichloromethane), the mixture of the effervescence agent (0.5 mol L{sup −1} Na{sub 2}CO{sub 3}) and the proton donor solution (1 mol L{sup −1} CH{sub 3}COOH). Formation of carbon dioxide microbubbles generated in situ leads to the dispersion of the extraction solvent in the whole aqueous sample and extraction of the analyte into organic phase. Unlike the conventional DLLME, in the case of EA-DLLME, the addition of dispersive solvent, as well as, time consuming centrifugation step for disruption of the cloudy state is avoided. The phase separation was achieved by gentle bubbling of nitrogen stream (2 mL min{sup −1} during 2 min). The performance of the suggested approach is demonstrated by determination of antipyrine in saliva samples. The procedure is based on the derivatization of antipyrine by nitrite-ion followed by EA-DLLME of 4-nitrosoantipyrine and subsequent UV–Vis detection using SWIA manifold. The absorbance of the yellow-colored extract at the wavelength of 345 nm obeys Beer's law in the range of 1.5–100 µmol L{sup −1} of antipyrine in saliva. The LOD, calculated from a blank test based on 3σ, was 0.5 µmol L{sup −1}. - Highlights: • First attempt to automate the effervescence assisted dispersive liquid–liquid microextraction. • Automation based on Stepwise injection analysis manifold in flow batch system. • Counterflow injection of extraction solvent and the effervescence agent. • Phase separation performed by gentle bubbling of nitrogen. • Application for the determination of antipyrine in saliva samples.

  6. Characterization of 60 Co y-radiation induced radical products of antipyrine by means of high performance liquid chromatography, mass spectrometry, capillary zone electrophoresis, micellar electrokinetic capillary chromatography and nuclear magnetic resonance spectrometry

    NARCIS (Netherlands)

    Coolen, S.A.J.; Everaerts, F.M.; Huf, F.A.

    1997-01-01

    Monitoring the amount of oxidative damage, caused by free radicals, is a major problem in free radical and aging research. Antipyrine is proposed as an exogenous marker for the biomolecular monitoring of oxidative stress. In this paper the characterization of the 60Co γ-radiation products of antipyr

  7. Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vinagre, A.M. [Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Collares, E.F. [Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2013-09-27

    Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg{sup −1}·day{sup −1}, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

  8. Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats.

    Science.gov (United States)

    Vinagre, A M; Collares, E F

    2013-09-01

    Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg-1·day-1, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean ± SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7 ± 1.6 vs 47.1 ± 2.3%) and of At (33.2 ± 2.3 vs 54.7 ± 3.6%) on GE and significantly reduced the effect of AA (48.1 ± 3.2 vs 67.2 ± 3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean ± SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1 ± 1.7 vs 46.9 ± 2.7%) and At (30.5 ± 1.7 vs 49 ± 3.2%) and significantly reduced the effect of AA (48.4 ± 2.6 vs 59.5 ± 3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

  9. Determination of Antipyrine and Caffeine Contents of Antipyriineand Caffeine Citrate Tablets by HPLC%HPLC法测定米格来宁片中安替比林与咖啡因的含量

    Institute of Scientific and Technical Information of China (English)

    刘震凌; 王佳楠

    2016-01-01

    目的:用HPLC法同时测定米格来宁片中安替比林与咖啡因的含量。方法采用 Waters C18色谱柱;以乙腈-水(20:80)为流动相;检测波长为273 nm。结果安替比林进样量在0.01412~0.70620μg、咖啡因进样量在0.00279~0.13960μg,均与峰面积呈良好的线性关系,安替比林、咖啡因的平均回收率与RSD分别为99.7%、0.6%,100.0%、0.5%(n=9)。结论该方法简便、准确,专属性强,重现性好,可用于该制剂的质量控制。%Objective We measured antipyrine and caffeine content in the Antipyriineand Caffeine Citrate Tablets by HPLC.Methods We used Waters C18 column, and used acetonitrile-water(20:80)as the mobile phase,and the detection wavelength was 273 nm.ResultsThe injection volume of antipyrine was 0.014 12 to 0.706 20 μg, and the injection volume of caffeine was 0.002 79 to 0.139 60 μg. They were associated with the peak area showed a good linear relationship. The antipyrine’s and caffeine’s average recovery and RSD respectively 99.7%,0.6%,100.0%,0.5%(n=9). ConclusionThe method is simple,accurate,specific,reproducible,and can be used for quality control of the preparation.

  10. 鲎试剂检测复方柳安咖注射液中细菌内毒素的可行性研究%Feasibility study on bacterial endotoxin of compound sodium salicylate antipyrine and caffeine injection with the TAL

    Institute of Scientific and Technical Information of China (English)

    赵祎; 张红宇; 王莉; 李海山

    2015-01-01

    Objective To establish a method for the bacterial endotoxin test of compound sodium salicylate antipyrine and caffeine injection.Method The bacterial endotoxin test was carried out according to the appendix XI E of Chinese Pharmacopoeia (Vol.Ⅱ, edition 2010).Result The compound sodium salicylate antipyrine and caffeine injection by diluting to a concentration of more than eighty times was noninterference for bacterial endotoxin test of gel -clot.Conclusion The bacterial endotoxins test is suitable for the detection of endotoxin in the compound sodium salicylate antipyrine and caffeine injection.%目的:通过对复方柳安咖注射液进行细菌内毒素检查法研究,建立复方柳安咖注射液细菌内毒素检查方法。方法:采用2010年版《中国药典》(二部)附录 XI E 细菌内毒素检查法进行。结果:复方柳安咖注射液经80倍及以上稀释,对细菌内毒素检查法(凝胶法)无干扰作用。结论:细菌内毒素检查法适用于复方柳安咖注射液中内毒素的检测。

  11. Effect of selective β-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats.

    Science.gov (United States)

    Vinagre, A M; Collares, E F

    2016-03-01

    There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

  12. Spectrophotometric determination of cadmium in wastewater with 1-(4-antipyrine)-3-(sulfanilic acid)-triazene%1-(4-安替比林)-3-(对苯磺酸)三氮烯光度法测定废水中镉(Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    陈文宾; 殷磊; 王琼; 马卫兴; 许兴友

    2011-01-01

    探讨了1-(4-安替比林)-3-(对苯磺酸)三氮烯(ASTA)与镉的反应,建立了直接测定废水中镉的光度分析方法.试验表明,在硼砂-氢氧化钠介质中,镉与ASTA形成1∶2的红色络合物,该络合物的最大吸收峰位于505 nm,表观摩尔吸光系数为2.7×105 L·mol-1·cm-1.10 mL溶液中,镉量在0.3~5.0 μg之间符合比尔定律,检出限为0.1 mg/L.方法已用于电镀废水样中镉的测定,结果与原子吸收光谱法相一致,方法的回收率在104%~105%之间,相对标准偏差(n=6)小于3.9%.%The reaction of l-(4-antipyrine)-3-( sulfanilic acid)-triazene ( AST A) with cadmium was studied to establish a direct photometric determination of cadmium in wastewater. The results showed that in the mixed medium of Na2B4O7-NaOH,cadmium reacted with ASTA to form a 1:2 red complex. The complex had maximum absorption at 505 nm with the apparent molar absorptivity of 2. 7× 105 L·mol-1·cm-1 0. 3-5. 0μg of Cd(II) obeyed Beer's law in 10 mL of solution and the detection limit Was 0. 1 mg/L. This method had been applied to the determination of cadmium in wastewater samples, whose results were in consistency obtained by AAS method. Recovery was in the range of 104%-105% and the RSD (n = 6) was lower than 3. 9%.

  13. Bio-important antipyrine derived Schiff bases and their transition metal complexes: Synthesis, spectroscopic characterization, antimicrobial, anthelmintic and DNA cleavage investigation

    Science.gov (United States)

    Manjunath, M.; Kulkarni, Ajaykumar D.; Bagihalli, Gangadhar B.; Malladi, Shridhar; Patil, Sangamesh A.

    2017-01-01

    Spectroscopic (IR, NMR, UV-vis, ESR, ESI-mass), magnetic and TGA studies suggests octahedral geometry for all the CoII, NiII and CuII complexes of the Schiff bases, derived from 4-aminoantipyrine and 8-formyl-7-Hydroxy-4-methylcoumarin/5-formyl-6-hydroxycoumarin, coordinated through ONO donor sites. Antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi), antifungal (Aspergillus niger, Aspergillus flavus and Cladosporium) and DNA cleavage properties of the metal complexes are investigated. The results suggested that some of the synthesized compounds are potential antimicrobials. The synthesized compounds tested for their anthelmintic activities and it was found that CoII and NiII complexes exhibited good anthelmintic properties.

  14. Meta-analysis of data from human ex vivo placental perfusion studies on genotoxic and immunotoxic agents within the integrated European project NewGeneris

    DEFF Research Database (Denmark)

    Mose, T; Mathiesen, L; Karttunen, V

    2012-01-01

    , medium and high transfer rate groups. The transfer rate differed slightly depending on the parameter used. However, compounds with passage similar to antipyrine which goes through the placenta by passive diffusion, and good recovery in media (no accumulation in the tissue or adherence to equipment) were...... after antipyrine normalization, we conclude that this normalization approach at least partially corrects the bias caused by the small methodological differences between studies....

  15. Synthesis of 1-(4-antipyrine)-3-(sulfanilic acid)-triazene and its color reaction with mercury( Ⅱ)%1-(4-安替比林)-3-(对苯磺酸)三氮烯的合成及其与汞(Ⅱ)的显色反应

    Institute of Scientific and Technical Information of China (English)

    陈文宾; 胡庆昊; 王琼; 郑秋霞; 马卫兴; 许兴友

    2010-01-01

    合成并鉴定了一种新的三氮烯试剂1-(4-安替比林)-3-(对苯磺酸)三氮烯(ASTA),研究了该试剂与Hg(Ⅱ)的显色反应条件,建立了一个测定汞(Ⅱ)的光度分析新方法.实验结果表明,在Tween-80溶液存在下,在硼砂-氢氧化钠介质中,ASTA与汞(Ⅱ)发生灵敏的显色反应,生成络合比为2:1的橙红色络合物.络合物的最大吸收峰位于488 nm,表观摩尔吸收系数为1.7×105L·mol-1·cm-1,在10 mL显色溶液中,汞(Ⅱ)量在0.5~15μg之间符合比尔定律,检出限为0.16 mg/L.该显色反应用于铅锌矿样品中汞(Ⅱ)的测定,测定结果与原子吸收光谱法相一致,加标回收率约为104%,相对标准偏差(n=6)≤4.4%.

  16. The effects of chronic infection of Fasciola hepatica on the metabolism and pharmacokinetics of antipyrine in water buffaloes%水牛慢性实验感染肝片吸虫对安替比林代谢动力学的影响

    Institute of Scientific and Technical Information of China (English)

    江善祥; Bayo,JE

    2000-01-01

    5头健康雄性去势水牛(2~3岁、体重300~500 kg),经粪便检查和Dot-ELISA检测确认无肝片吸虫感染.每头每天口服60个肝片吸虫囊蚴,连续20 d,共感染1 200个囊蚴,用以研究水牛慢性感染(少量多次感染)肝片吸虫对安替比林代谢动力学的影响.每周定时由颈静脉采血,测定血清酶水平变化.于感染前、感染后急性期及慢性期进行安替比林动力学试验.由颈静脉瘘管收集血样,用尿液收集器收集尿样,用HPLC法分析血浆安替比林动力学参数及尿安替比林清除率.结果表明:水牛慢性实验性感染肝片吸虫呈亚临床状态,AP的血浆及尿代谢物清除率在急性期分别下降了48%和61.91%,慢性期逐步恢复.

  17. The Effects of Acute Infection of Fasciola hepatica on the Metabolism and Pharmacokinetics of Antipyrine in Water Buffaloes%水牛急性实验感染肝片吸虫对安替比林代谢动力学的影响

    Institute of Scientific and Technical Information of China (English)

    江善祥; 毛鑫智; Bayon J E; Gonalez-Gallego J

    2003-01-01

    5头健康雄性去势水牛(2~3岁、体重300~500 kg),经粪便和Dot-ELISA检测确认无肝片吸虫感染.每头水牛一次经口感染1600个肝片吸虫囊蚴,研究急性感染(一次大剂量)肝片吸虫对水牛安替比林代谢动力学影响.用HPLC法测定血浆安替比林(AP)及其代谢物的浓度,分析其动力学参数.每周定时采血测定血清酶水平变化.结果表明:水牛急性感染肝片吸虫后急性期安替比林静脉给药后的动力学参数没有显著变化,在慢性期,血浆消除半衰期T1/2β延长41.42%,总消除率CL下降60.10%,表观分布容积Vdss减小43.61%,平均保留时间MRT上升41.16%,血浆浓度-时间曲线下面积AUC增大150.61%.AP给药后48 h内各代谢物的形成比率及尿清除率与对照期相比在急性期无显著差异,而慢性期极显著降低,AP试验结果与血浆酶水平变化相一致.

  18. Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Rytting, Erik; Mose, Tina;

    2009-01-01

    the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine approximately antipyrine>benzoic acid>glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations....... Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport...... across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare...

  19. Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.

    Science.gov (United States)

    Thompson, G A; St Peter, J V; Heise, M A; Horowitz, Z D; Salyers, G C; Charles, T T; Brezovic, C; Russell, D A; Skare, J A; Powell, J H

    1996-11-01

    The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.

  20. Synthesis, Spectral and Thermal Properties of Some Penta-Coordinated Complexes of Oxovanadium(IV) Derived from Thiosemicarbazones of 4-Aminoantipyrine

    OpenAIRE

    Agarwal, Ram K. [رام اجراول; Prasad, Surendra; GAHLOT, Neetu

    2004-01-01

    The paper reports the synthesis of crystalline oxovanadium(IV), VO2+, complexes of thiosemicarbazones, i.e. 4[N-(4'-nitrobenzalidene)amino]antipyrine thiosemicarbazone (4'-NO2BAAPTS) and 4[N-(furan-2'-aldimine)amino]antipyrine thiosemicarbazone (FFAAPTS) with general composition VOX2L (X = Cl, Br, I, NO3 or NCS) and VO(ClO4)2(L)H2O (L = 4'-NO2BAAPTS or FFAAPTS). All the complexes were characterized by elemental analyses, molar mass, molar conductance, magnetic susc...

  1. On the pathogenesis of bedsores. Skin blood flow cessation by external pressure on the back

    DEFF Research Database (Denmark)

    Larsen, B; Holstein, P; Lassen, N A

    1979-01-01

    -antipyrine mixed with histamine. The external pressure was measured by a small airfilled plastic cushion connected to a mercury manometer. In 11 normal subjects, eight patients with hypertension and seven patients with tetra- or paraplegia the "flow cessation external pressure" (FCEP) was strongly correlated...

  2. Kinetics of silica nanoparticles in the human placenta

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Mose, Tina; Maroun, Lisa Leth;

    2015-01-01

    choriocarcinoma cell line and the ex vivo perfused human placenta. Nanotoxicity in BeWo cells was examined by the MTT assay which demonstrated decreased cell viability at concentrations >100 µg/mL. In the placental perfusion experiments, antipyrine crossed the placenta rapidly, with a foetal:maternal ratio of 0...

  3. Creation of recognition sites for organophosphate esters based on charge transfer and ligand exchange imprinting methods.

    Science.gov (United States)

    Say, Ridvan

    2006-10-01

    This manuscript describes a method for the selective binding behavior of paraoxan and parathion compounds on surface imprinted polymers which were prepared using both charge transfer (CT) (methacryloyl-antipyrine, MAAP) and ligand-exchange (LE) (methacryloyl-antipyrine-gadalonium, MAAP-Gd) monomers. These polymers were prepared in the presence of azobisisobutyronitrile (AIBN) as an initiator and crosslinking EDMA and were imprinted with organophosphate esters. Influence of CT and LE imprinting on the creation of recognition sites toward paraoxan and parathion was determined applying adsorption isotherms. The effect of initial concentration of paraoxan and parathion, adsorption time and imprinting efficiency on adsorption selectivity for MIP-CT and MIP-LE was investigated. Association constant (K(ass)), number of accessible sites (Q(max)), relative selectivity coefficient (k') and binding ability were also evaluated.

  4. Drug metabolism and genetic polymorphism in subjects with previous halothane hepatitis

    DEFF Research Database (Denmark)

    Ranek, L; Dalhoff, K; Poulsen, H E

    1993-01-01

    To test the hypothesis that halothane hepatitis is caused by a combination of altered drug metabolism and an immunoallergic disposition, the metabolism of antipyrine, metronidazole, sparteine, phenytoin, and racemic R- and S-mephenytoin was investigated in seven subjects with previous halothane...... hepatitis do not appear to be different from controls with regard to drug metabolism and HLA tissue type. The possibility of a higher frequency of complement C3 phenotype F and FS needs further investigation....... hepatitis. The HLA tissue types and the complement C3 phenotypes were also determined. The metabolism of antipyrine and metronidazole was within normal range in all subjects, and they were all fast or extensive metabolizers of sparteine, mephenytoin, and phenytoin. HLA tissue types were unremarkable. Five...

  5. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    Science.gov (United States)

    Tanaka, E; Nakamura, K

    1989-08-01

    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not affected. After roxatidine acetate, the pharmacokinetics of AP and TMO were unchanged. The cumulative renal excretion (% dose) and formation clearance of 3-hydroxymethyl-3-nor-antipyrine (NORA) were lowered by cimetidine treatment, but not following the administration of roxatidine acetate. ICG clearance was not changed significantly by either pretreatment. The results of this study show that roxatidine acetate does not impair the metabolism of three model substrates used to assess hepatic drug clearance.

  6. Interaction of roxatidine acetate with antacids, food and other drugs.

    Science.gov (United States)

    Labs, R A

    1988-01-01

    The inhibition of hepatic mixed-function oxidase microsomal enzymes by cimetidine can lead to clinically important drug interactions. The metabolism of antipyrine is used as an index of hepatic enzymatic activity. The pharmacokinetic profiles of salivary antipyrine obtained following treatment with roxatidine acetate 75 mg or placebo twice a day for 7 days showed similar characteristics with no difference in the areas under the plasma concentration-time curves. In addition, roxatidine acetate 75 mg daily did not modify the clearance of propranolol, diazepam, desmethyldiazepam or controlled release theophylline preparations. Furthermore, there was no interference in the bioavailability of roxatidine acetate 150 mg daily when administered alone or in combination with a meal or antacids.

  7. 1,5-Dimethyl-4-(1-methyl-3-oxo-3-phenylprop-1-enylamino-2-phenyl-1H-pyrazol-3(2H-one

    Directory of Open Access Journals (Sweden)

    Hualing Zhu

    2011-07-01

    Full Text Available In the title compound, C21H21N3O2, an intramolecular N—H...O interaction generates an S(6 ring, which stablizes the enamine–keto tautomer. The S(6 ring makes dihedral angles of 33.07 (7, 56.50 (8 and 38.59 (8°, respectively, with the benzoylacetone benzene ring and the antipyrine pyrazole and benzene rings.

  8. The impact of cocaine and heroin on the placental transfer of methadone

    Directory of Open Access Journals (Sweden)

    Wenzinger Silvana

    2009-06-01

    Full Text Available Abstract Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24 were ex-vivo perfused with medium (m (control, n = 6, m plus methadone (n = 6, m plus methadone and cocaine (n = 6 or m plus methadone and heroin (n = 6. Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin, microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.

  9. The impact of cocaine and heroin on the placental transfer of methadone

    Science.gov (United States)

    Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula

    2009-01-01

    Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast. PMID:19519880

  10. Utility of 4-formylantipyrine in heterocyclic synthesis

    Directory of Open Access Journals (Sweden)

    Abdou O. Abdelhamid

    2010-04-01

    Full Text Available Pyrrolo[3,4-c]pyrazole-4,6(1H,5H-dione, pyrano[2,3-c]pyrazole-5-carbonitrile, pyrano[2,3-d]4-imidazolines, pyrido[2,1-b]benzimidazole, pyrido[2,1-b][1,3]benzoxazole, pyrido[2,1-b][1,3]benzothiazole and pyrido[2,1-b]quinazoline were synthesised from antipyrine derivatives with appropriate reagents such as maleimides, malononitrile, ethyl cyanoacetate, benzimidazole-2-acetonitrile, benzothiazole-2-acetonitrile, benzoxazol-2-acetonitrile, benzoylacetonitrile and other reagents. The newly synthesised compounds were established by elemental analysis, spectral data, and alternative synthetic routes whenever possible.

  11. Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt Extrusion and Film Coating

    OpenAIRE

    Jedinger, Nicole; Schrank, Simone; Fischer, Johannes M.; Breinhälter, Karlheinz; Khinast, Johannes; Roblegg, Eva

    2015-01-01

    This study focused on the development of flexible (i.e., deformable) multiple-unit pellets that feature (i) a prolonged drug release, (ii) drug abuse deterrence, and (iii) a minimal risk of alcohol-induced dose dumping (ADD). Deformable pellets were prepared via an advanced continuous one-step hot-melt extrusion (HME) technique, with the drug (i.e., antipyrine and codeine phosphate) fed as an aqueous solution into the molten matrix material (i.e., cornstarch, gum arabic, and xanthan). Formula...

  12. Transfer in vitro of three benzodiazepines across the human placenta.

    Science.gov (United States)

    Guerre-Millo, M; Rey, E; Challier, J C; Turquais, J M; d'Athis, P; Olive, G

    1979-04-17

    A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.

  13. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    OpenAIRE

    1989-01-01

    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not af...

  14. The effects of estrus cycle on drug metabolism in the rat.

    Science.gov (United States)

    Brandstetter, Y; Kaplanski, J; Leibson, V; Ben-Zvi, Z

    1986-01-01

    The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.

  15. L'absurde dans le théâtre français Dada et présurréaliste

    OpenAIRE

    Kunesova, Mariana

    2014-01-01

    The aim of this doctoral dissertation is to analyze the absurd as an aesthetic category in French Dada and pre-surrealist theatre between 1916 and 1923, dealing with three texts : La Première aventure céleste de Monsieur Antipyrine by Tristan Tzara (1916), S’il vous plaît, by André Breton et Philippe Soupault (written in 1919) and Les Mystères de l’amour by Roger Vitrac (written in 1923).The absurd as a theatre and drama category was examined especially at the half of the last century by the ...

  16. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

    Mathiesen, Line; Mose, Tina; Mørck, Thit Juul;

    2010-01-01

    the placental perfusion model in Copenhagen including control substances. The positive control substance antipyrine shows no difference in transport regardless of perfusion media used or of terms of delivery (n=59, pmarked dextran correspond with leakage criteria (...mlh(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100ml fetal perfusion media. Success rate of the Copenhagen placental perfusions is provided in this study, including considerations and quality control parameters. Three checkpoints suggested to determine success rate...

  17. Application of organogels as oral controlled release formulations of hydrophilic drugs.

    Science.gov (United States)

    Iwanaga, Kazunori; Kawai, Mineo; Miyazaki, Makoto; Kakemi, Masawo

    2012-10-15

    We previously demonstrated that organogels prepared from soybean oil using 12-hydroxy stearic acid as a gelator can slowly release ibuprofen, a model lipophilic drug. In this study, we investigated the applicability of organogels as controlled release formulations of hydrophilic drugs. The release rates of theophylline and ofloxacin, which are used as model hydrophilic drugs, were significantly slower than those of ibuprofen and antipyrine (model lipophilic drugs). Furthermore, no erosion was noted during drug release from organogels. Lipophilic drug molecules are released after diffusion in organogels because all molecules fully dissolve in the gel. On the other hand, hydrophilic drug molecules need to be dissolved before they diffuse in the organogel, prior to their release from the gel. Therefore, it is speculated that the release rates of hydrophilic drugs are slower than those of lipophilic drugs. To confirm the usefulness of organogels in controlled release formulations in vivo, organogels containing ibuprofen, ofloxacin, theophylline or antipyrine were intraduodenally administered to rats. All drugs used in this study were rapidly absorbed when administered in aqueous suspensions. In contrast, the drug concentrations in plasma after administration in organogels were lower; however, the lower concentrations of drugs sustained for 10 h after administration. With organogel administration, the mean residence time of drugs was longer than that with aqueous suspension administration. In conclusion, organogels are potential candidates for controlled release formulations of not only lipophilic drugs, but also hydrophilic drugs.

  18. Why amphibians are more sensitive than mammals to xenobiotics.

    Directory of Open Access Journals (Sweden)

    Angelo Quaranta

    Full Text Available Dramatic declines in amphibian populations have been described all over the world since the 1980s. The evidence that the sensitivity to environmental threats is greater in amphibians than in mammals has been generally linked to the observation that amphibians are characterized by a rather permeable skin. Nevertheless, a numerical comparison of data of percutaneous (through the skin passage between amphibians and mammals is lacking. Therefore, in this investigation we have measured the percutaneous passage of two test molecules (mannitol and antipyrine and three heavily used herbicides (atrazine, paraquat and glyphosate in the skin of the frog Rana esculenta (amphibians and of the pig ear (mammals, by using the same experimental protocol and a simple apparatus which minimizes the edge effect, occurring when the tissue is clamped in the usually used experimental device.The percutaneous passage (P of each substance is much greater in frog than in pig. LogP is linearly related to logKow (logarithm of the octanol-water partition coefficient. The measured P value of atrazine was about 134 times larger than that of glyphosate in frog skin, but only 12 times in pig ear skin. The FoD value (Pfrog/Ppig was 302 for atrazine, 120 for antipyrine, 66 for mannitol, 29 for paraquat, and 26 for glyphosate.The differences in structure and composition of the skin between amphibians and mammals are discussed.

  19. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T. (Faculty of Pharmaceutical Sciences, Setsunan University, Osaka (Japan))

    1991-06-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain.

  20. Lung damage and pulmonary uptake of serotonin in intact dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

    1985-06-01

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.

  1. Why amphibians are more sensitive than mammals to xenobiotics.

    Science.gov (United States)

    Quaranta, Angelo; Bellantuono, Vito; Cassano, Giuseppe; Lippe, Claudio

    2009-11-04

    Dramatic declines in amphibian populations have been described all over the world since the 1980s. The evidence that the sensitivity to environmental threats is greater in amphibians than in mammals has been generally linked to the observation that amphibians are characterized by a rather permeable skin. Nevertheless, a numerical comparison of data of percutaneous (through the skin) passage between amphibians and mammals is lacking. Therefore, in this investigation we have measured the percutaneous passage of two test molecules (mannitol and antipyrine) and three heavily used herbicides (atrazine, paraquat and glyphosate) in the skin of the frog Rana esculenta (amphibians) and of the pig ear (mammals), by using the same experimental protocol and a simple apparatus which minimizes the edge effect, occurring when the tissue is clamped in the usually used experimental device.The percutaneous passage (P) of each substance is much greater in frog than in pig. LogP is linearly related to logKow (logarithm of the octanol-water partition coefficient). The measured P value of atrazine was about 134 times larger than that of glyphosate in frog skin, but only 12 times in pig ear skin. The FoD value (Pfrog/Ppig) was 302 for atrazine, 120 for antipyrine, 66 for mannitol, 29 for paraquat, and 26 for glyphosate.The differences in structure and composition of the skin between amphibians and mammals are discussed.

  2. Effect of Fluosol-DA hemodilution on the kinetics of hepatically eliminated drugs.

    Science.gov (United States)

    Shrewsbury, R P

    1987-03-01

    The pharmacokinetics of four hepatically eliminated drugs were determined in the rat following moderate hemodilution with either Fluosol-DA or normal saline. The drugs, antipyrine, phenytoin, indocyanine green, and d-propranolol, have extraction ratios from 0.01 to 0.99 in the rat. Animals received an intravenous dose of the drug 0.5, 24, 48, or 72 hours after hemodilution and drug disposition was compared to non-exchanged animals. Antipyrine clearance was increased 48 and 72 hours after Fluosol-DA exchange probably due to enhanced microsomal enzymatic activity. Indocyanine green clearance was decreased 24 hours after Fluosol-DA exchange more likely by a change in its extraction ratio than by alterations in hepatic blood flow. Phenytoin and d-propranolol clearances were decreased at 24 and 72 hours respectively after Fluosol-DA hemodilution due to a decreased apparent volume of distribution. Saline hemodilution decreased phenytoin clearance 24, 48, and 72 hours after exchange also by decreasing the apparent volume of distribution. This volume change was thought to be due to hypovolemia or a microcirculation redistribution which was secondary to hemodilution.

  3. Assessment of blood brain barrier penetration of drugs using a rat steady-state brain distribution model%大鼠稳态脑分布模型评价药物的血脑屏障通透性

    Institute of Scientific and Technical Information of China (English)

    原梅; 阳海鹰; 钟玉环; 庄笑梅; 李桦

    2015-01-01

    目的 建立大鼠稳态脑分布模型用于评价安替比林、阿替洛尔和ZZB 系列新药候选化合物的稳态脑分布和血脑屏障通透性.方法 大鼠静脉推注负荷剂量的药物后恒量输注使血药浓度达到稳态,取血和脑组织样品,LC-MS/MS 定量测定血浆和脑组织药物浓度,计算稳态脑血比值(Kp值).在Caco-2 单层细胞体外模型上评价受试药物的双向跨膜通透性,计算表观通透系数(Papp).结果 安替比林和阿替洛尔分别为已知的血脑屏障易通透和难通透药物.安替比林的平均稳态脑分布浓度为(2561±125)ng/g,Kp值为0.93±0.04.阿替洛尔则分别为(20.1±0.8)ng/g 和0.015±0.002.安替比林的Kp值约为阿替洛尔的60 倍.ZZB 系列化合物的结构相似,但Kp值的差异较大,从0.044 到6.41,并与Caco-2 细胞模型的Papp值不相关.结论 建立的大鼠稳态脑分布模型可快速形成稳态血浆浓度,适用于药物血脑屏障通透程度的评价,方法简单、可靠且经济.%Objective To develop a steady-state brain distribution model in rats and to assess the blood brain barrier(BBB) penetration of antipyrine, atenolol and a group of ZZB candidate compounds. Methods Antipyrine, atenolol and ZZB compounds were administered to rats by an initial iv bolus dose (loading dose) followed by iv infusion at a constant rate for 30-40 min to reach steady-state plasma kinetics. The blood and brain tissue samples were then collected. The steady-state concentrations of the samples were measured by LC-MS/MS. The steady-state ratio of brain to plasma concentration (Kp) was calculated. The drugs and candidate compounds were also tested with Caco-2 cell model and the apparent bidirectional transport permeability coefficient (Papp) was obtained. Results Antipyrine and atenolol were known as drugs with high and low BBB penetration properties respectively. The mean brain concentrations of antipyrine and atenolol at steady-state were(2561 ± 125) and(20.1

  4. Ligand exchange and MIP-based paraoxon memories onto QCM sensor

    Science.gov (United States)

    Birlik Özkütük, Ebru; Emir Diltemiz, Sibel; Özalp, Elif; Uzun, Lokman; Ersöz, Arzu

    2015-04-01

    In this study, we have aimed to prepare quartz crystal microbalance (QCM) sensor using paraoxon-imprinted particles. Firstly, methacryloyl antipyrine (MAAP)-based metal-chelate-coordinated pre-complex has been prepared and used for paraoxon templation. Then, paraoxon-imprinted nanofilms were formed on QCM sensor after modification of the gold surfaces with allyl mercaptan. By this way, specific and selective memories, which depend on metal-chelate interactions between Eu(III) ions and template, for paraoxon molecules have been obtained on the electrode surface. QCM sensor has characterized using AFM and ellipsometer. The detection limit and the affinity constant have found to be 0.09 μM and 5.71 × 103 M-1 for MAAP-Eu paraoxon-based nanofilm, respectively. The specificity of the QCM sensor has shown using parathion as a competitor molecule.

  5. Could quantitative liver function tests gain wide acceptance among hepatologists?

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino

    2009-01-01

    It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-bystep disease progression; surgical risk; and efficacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test (not necessarily a laboratory one) to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests? Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.

  6. Wound healing in below-knee amputations in relation to skin perfusion pressure

    DEFF Research Database (Denmark)

    Holstein, P; Sager, P; Lassen, N A

    1979-01-01

    In 60 below-knee amputations the healing of the stumps was correlated with the local skin perfusion pressure (SPP) measured preoperatively as the external pressure required to stop isotope washout using 131I- or 125I--antipyrine mixed with histamine. Of the eight cases with an SPP below 20 mm......Hg, no less than six (75 per cent) failed to heal and required reamputation at the above-knee level. Of the 12 cases with an SPP between 20 and 30 mmHg four cases (33 per cent) failed to heal but of the 40 cases with an SPP above 30 mmHg, there were only four cases (10 per cent) which did not heal...... closely to the postoperative clinical course. We conclude that a low SPP can be used to predict ischaemic wound complications, leading to reamputation at a higher level....

  7. Wound healing in above-knee amputations in relation to skin perfusion pressure

    DEFF Research Database (Denmark)

    Holstein, P; Dovey, H; Lassen, N A

    1979-01-01

    In 59 above-knee amputations healing of the stumps was correlated with the local skin perfusion pressure (SPP) measured preoperatively as the external pressure required to stop isotope washout using 1318-- or 125I--antipyrine mixed with histamine. Out of the 11 cases with an SPP below 30 mm......Hg no less than nine (82 per cent) suffered severe wound complications. Out of the 48 cases with an SPP above 30 mmHg severe wound complications occurred in only four cases (8 per cent). The difference in wound complication rate is highly significant (P less than 0.01). The postoperative SPP measured...... on the stumps was on average only slightly and insignificantly higher than the preoperative values, explaining why the preoperative values related so closely to the postoperative clinical course. We conclude that the SPP can be used to predict ischaemic wound complications in above-knee amputations as has...

  8. In Situ Formation of Steroidal Supramolecular Gels Designed for Drug Release

    Directory of Open Access Journals (Sweden)

    Hana Bunzen

    2013-03-01

    Full Text Available In this work, a steroidal gelator containing an imine bond was synthesized, and its gelation behavior as well as a sensitivity of its gels towards acids was investigated. It was shown that the gels were acid-responsive, and that the gelator molecules could be prepared either by a conventional synthesis or directly in situ during the gel forming process. The gels prepared by both methods were studied and it was found that they had very similar macro- and microscopic properties. Furthermore, the possibility to use the gels as carriers for aromatic drugs such as 5-chloro-8-hydroxyquinoline, pyrazinecarboxamide, and antipyrine was investigated and the prepared two-component gels were studied with regard to their potential applications in drug delivery, particularly in a pH-controlled drug release.

  9. Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system

    DEFF Research Database (Denmark)

    Myllynen, Päivi; Mathiesen, Line; Weimer, Marc

    2010-01-01

    As a part of EU-project ReProTect, a comparison of the dual re-circulating human placental perfusion system was carried out, by two independent research groups. The detailed placental transfer data of model compounds [antipyrine, benzo(a)pyrene, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b......)pyridine) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline] has been/will be published separately. For this project, a comparative re-analysis was done, by curve fitting the data and calculating two endpoints: AUC(120), defined as the area under the curve between time 0 and time 120min and as t(0.5), defined...

  10. Dual-isotope measurement of lung water

    Energy Technology Data Exchange (ETDEWEB)

    Chu, R.Y.L.; Carlile, P.V. Jr.; Basmadjian, G. (Oklahoma Univ., Oklahoma City, OK (USA). Health Sciences Center Oklahoma Univ., Oklahoma City, OK (USA). Veterans Administration Medical Center)

    1989-01-01

    Iodine-131-labeled iodo-antipyrine and {sup 99m}Tc-labeled erythrocytes were used to measure water content in lungs. These radioactive tracers were injected into 11 dogs with injured lungs. Blood samples were drawn and the animals sacrificed. The lungs were removed, weighed and homogenized. Samples of blood and lung homogenate were assayed for {sup 131}I and {sup 99m}Tc. Samples were also weighed before and after drying to a constant weight at 70-76{sup 0}C. Extravascular lung water was determined by the dual-isotope technique and again by gravimetric analysis. The average ratio of the results from the two different methods was 1.14{plus minus}0.20. The two methods were also compared by regression analysis and the correlation coefficient was 0.97{plus minus}0.09. (author).

  11. Intramolecular proton transfer through the adjoining π-conjugated system in Shiff base: Application for colorimetric sensing of fluoride anion

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xudong, E-mail: 081022009@fudan.edu.cn [College of Chemistry and Material Sciences, Hebei Normal University, Yuhua Road 113, Shijiazhuang 050024 (China); College of Science and Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science and Technology, Yuhua Road 70, Shijiazhuang 050080 (China); Zhang, Ping [College of Chemistry and Material Sciences, Hebei Normal University, Yuhua Road 113, Shijiazhuang 050024 (China); Li, Yajuan; Zhen, Xiaoli; Geng, Lijun; Wang, Yanqiu [College of Science and Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science and Technology, Yuhua Road 70, Shijiazhuang 050080 (China); Ma, Zichuan, E-mail: ma7405@hebtu.edu.cn [College of Chemistry and Material Sciences, Hebei Normal University, Yuhua Road 113, Shijiazhuang 050024 (China)

    2014-07-01

    In this paper, a new kind of phenol-based chemsensor L2 comprised of a Schiff base and azo groups was rationally designed and synthesized. It could selectively recognize fluoride anion among tested anions such as F{sup −}, AcO{sup −}, H{sub 2}PO{sub 4}{sup −}, Cl{sup −}, Br{sup −}, and I{sup −} with obvious color changes from yellow to fuchsia. The intramolecular PT (proton transfer) in L1 and L2 was responsible for the sensing ability, which was certified by the {sup 1}H NMR and Uv–vis experiments. - Highlights: • The phenol derivative L2 could selectively sense F{sup −} among test anions. • Intramolecular proton transfer happened when L2 was bonded with F{sup −}. • It is the first antipyrine-based anion receptor.

  12. Synthesis, physicochemical studies and biological evaluation of unimetallic and heterobimetallic complexes of hexadentate dihydrazone ligands

    Directory of Open Access Journals (Sweden)

    Fathy A. El Saied

    2017-03-01

    Full Text Available A new coordination unimetallic and heterobimetallic complexes of hexadentate N2O4 donor dihydrazone ligands were prepared by the condensation of 4-formyl antipyrine with adipic dihydrazide and succinic dihydrazide. The ligands (1 and (11 and their complexes thoroughly characterized using various analytical, physical and spectroscopic techniques, which indicate a distorted octahedral geometry around the metal ions. The ESR spectra of solid copper(II complexes (2–4 and (12–14 showed axial symmetry with g||>g⊥ > ge, indicating distorted octahedral structure and the presence of the unpaired electron in a d(x2−y2 orbital with significant covalent bond character. The antimicrobial activity results of the metal compounds (2–5, (7, (10, (12–15 and (17 show that, all these complexes exhibit inhibitory moderate to mild effects towards Bacillus subtilis, Escherichia coli and Aspergillus niger.

  13. Efficient and Convenient Route for the Synthesis of Some New Antipyrinyl Monoazo Dyes: Application to Polyester Fibers and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Ahmed A. Fadda

    2013-01-01

    Full Text Available Nine variously substituted azo dye derivatives 2–10 of antipyrine were prepared. The effects of the nature and orientation of the substituents on the color and dyeing properties of these dyes for polyester fibers were evaluated. The newly synthesized compounds were characterized on the basis of elemental analyses and spectral data. On the other hand, the investigated dyes were applied to polyester fabrics and showed good light, washing, heat, and acid perspiration fastness. The remarkable degree of brightness after washings is indicative of the good penetration and the excellent affinity of these dyes for the fabric. The results in general revealed the efficiency of the prepared compounds as new monoazo disperse dyes. The newly synthesized compounds were screened for their antioxidant and cytotoxic activity against Vitamin C and 5-fluorouracil, respectively. The data showed clearly that most of the compounds exhibited good antioxidant and cytotoxic activities.

  14. Functionalized magnesium organometallics as versatile intermediates for the synthesis of polyfunctional heterocycles.

    Science.gov (United States)

    Ila, Hiriyakkanavar; Baron, Oliver; Wagner, Andreas J; Knochel, Paul

    2006-02-14

    In the last few years, we have demonstrated that the halogen/magnesium-exchange reaction is a unique method for preparing a variety of new functionalized aryl, alkenyl, heteroaryl magnesium compounds which has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. A variety of functional groups such as an ester, nitrile, iodide, imine and even sensitive groups like nitro, hydroxyl and boronic ester can be tolerated in these organomagnesium compounds. We wish to describe the application of this halogen/magnesium-exchange reaction for the preparation of a broad range of five- and six-membered functionalized heteroaryl magnesium compounds and their reactions with various electrophiles providing a new entry to a range of polyfunctional heterocycles such as thiophene, furan, pyrrole, imidazole, thiazole, antipyrine, pyridine, quinoline and uracil derivatives.

  15. The double isotope technique for in vivo determination of the tissue-to-blood partition coefficient for xenon in human subcutaneous adipose tissue--an evaluation

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Astrup, A; Bülow, J

    1985-01-01

    Local subcutaneous 133xenon (133Xe) elimination was registered in the human forefoot in 34 patients. The tissue/blood partition coefficient for Xe was estimated individually by simultaneous registration of 133Xe and [131I]antipyrine ([131I]AP) washout from the same local depot. When measured...... in this way, an average partition coefficient for Xe was found to be 4.3 +/- 1.23 ml g-1. This value is significantly lower than the partition coefficient found in a previous in vitro study in which a Xe partition coefficient of 7.5 +/- 1.57 ml g-1 was found. Thus, if the local blood flow is calculated using...... the partition coefficient found by the double isotope technique, significantly lower values are obtained than if the in vitro determined coefficient is used. This difference is explained mainly by local dilution when injecting xenon subcutaneously. In short-term studies, utilization of the double isotope...

  16. Copper(II Complexes with Ligands Derived from 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one: Synthesis and Biological Activity

    Directory of Open Access Journals (Sweden)

    Raluca Cernat

    2006-11-01

    Full Text Available The synthesis of Cu(II complexes derived from Schiff base ligands obtainedby the condensation of 2-hydroxybenzaldehyde or terephtalic aldehyde with 4-amino-antipyrine (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one is presented. The newlyprepared compounds were characterized by 1H-NMR, UV-VIS, IR and ESRspectroscopy. The determination of the antimicrobial activity of the ligands and of thecomplexes was carried out on samples of Escherichia coli, Klebsiella pneumoniae,Acinetobacter boumanii, Pseudomonas aeruginosa, Staphylococcus aureus and Candidasp. The qualitative and quantitative antimicrobial activity test results proved that all theprepared complexes are very active, especially against samples of Ps. aeruginosa, A.Boumanii, E. coli and S. aureus.

  17. Research review: interactions between environmental chemicals and drug biotransformation in man

    Energy Technology Data Exchange (ETDEWEB)

    Alvares, A.P.

    1978-11-01

    Besides genetic factors, environmental factors play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Dietary factors may also play a significant role in the regulation of drug metabolism. Such intentional or unintentional exposure to environmental chemicals indicates the importance of individualisation of drug therapy.

  18. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Tsutsui, H.; Tomoike, H.; Nakamura, M. (Kyushu Univ., Fukuoka (Japan))

    1990-08-01

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using ({sup 14}C)antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of ({sup 14}C)antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.

  19. A novel combined solar pasteurizer/TiO2 continuous-flow reactor for decontamination and disinfection of drinking water.

    Science.gov (United States)

    Monteagudo, José María; Durán, Antonio; Martín, Israel San; Acevedo, Alba María

    2017-02-01

    A new combined solar plant including an annular continuous-flow compound parabolic collector (CPC) reactor and a pasteurization system was designed, built, and tested for simultaneous drinking water disinfection and chemical decontamination. The plant did not use pumps and had no electricity costs. First, water continuously flowed through the CPC reactor and then entered the pasteurizer. The temperature and water flow from the plant effluent were controlled by a thermostatic valve located at the pasteurizer outlet that opened at 80 °C. The pasteurization process was simulated by studying the effect of heat treatment on the death kinetic parameters (D and z values) of Escherichia coli K12 (CECT 4624). 99.1% bacteria photo-inactivation was reached in the TiO2-CPC system (0.60 mg cm(-2) TiO2), and chemical decontamination in terms of antipyrine degradation increased with increasing residence time in the TiO2-CPC system, reaching 70% degradation. The generation of hydroxyl radicals (between 100 and 400 nmol L(-1)) was a key factor in the CPC system efficiency. Total thermal bacteria inactivation was attained after pasteurization in all cases. Chemical degradation and bacterial photo-inactivation in the TiO2-CPC system were improved with the addition of 150 mg L(-1) of H2O2, which generated approximately 2000-2300 nmol L(-1) of HO(●) radicals. Finally, chemical degradation and bacterial photo-inactivation kinetic modelling in the annular CPC photoreactor were evaluated. The effect of the superficial liquid velocity on the overall rate constant was also studied. Both antipyrine degradation and E. coli photo-inactivation were found to be controlled by the catalyst surface reaction rate.

  20. Two-photon absorption, nonlinear optical and UV-vis spectral properties of 2-furanylmethyleneaminoantipyrine, benzylideneaminoantipyrine and cinnamilideneaminoantipyrine

    Energy Technology Data Exchange (ETDEWEB)

    Sun Yuxi, E-mail: yuxisun@163.com [Key Laboratory for Soft Chemistry and Functional Materials of Education Ministry, Nanjing University of Science and Technology, Nanjing 210094 (China) and Key Laboratory of Life-Organic Analysis, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165 (China); Hao Qingli; Tang Weihua; Wang Yufeng [Key Laboratory for Soft Chemistry and Functional Materials of Education Ministry, Nanjing University of Science and Technology, Nanjing 210094 (China); Yang Xujie, E-mail: yangx@mail.njust.edu.cn [Key Laboratory for Soft Chemistry and Functional Materials of Education Ministry, Nanjing University of Science and Technology, Nanjing 210094 (China); Lu Lude; Wang Xin [Key Laboratory for Soft Chemistry and Functional Materials of Education Ministry, Nanjing University of Science and Technology, Nanjing 210094 (China)

    2011-09-15

    Highlights: {yields} Three imine-bridged aromatic antipyrine derivatives as photo-responsive materials. {yields} The compounds exhibit two-photon absorption and first-hyperpolarization properties {yields} The compounds have long-range electron transfer characteristics. - Abstract: Organic compounds as functional materials have attracted much keen interest in the past three decades owing to their potential applications in science and technology. Currently, great efforts have been made in looking for suitable photo-responsive materials among the multifarious organic compounds. Herein we reported the photophysical properties of 2-furanylmethylene-aminoantipyrine (FMAAP), benzylideneaminoantipyrine (BIAAP) and cinnamilideneamino-antipyrine (CIAAP) studied by a combined experimental and theoretical investigation. Two-photon absorption measurements give the cross-section values of 1.350 x 10{sup -50} cm{sup 4} s/photon for FMAAP, 1.046 x 10{sup -50} cm{sup 4} s/photon for BIAAP and 2.047 x 10{sup -50} cm{sup 4} s/photon for CIAAP. The calculated first-hyperpolarization values are of 2.303 x 10{sup -30}, 1.257 x 10{sup -29}, 2.889 x 10{sup -29} cm{sup 5}/esu for FMAAP, BIAAP and CIAAP, respectively. UV-vis spectroscopy technique further reveals that the studied compounds display long-range electron transfer characteristics by absorbing light of specific wavelengths of 294.5 nm for FMAAP, 293.2 nm for BIAAP and 303.1 nm for CIAAP. All the results indicate that the studied compounds are promising candidates of functionally photo-responsive materials.

  1. Evaluation of the effect of TM208 on the activity of five cytochrome P450 enzymes using on-line solid-phase extraction HPLC-DAD: a cocktail approach.

    Science.gov (United States)

    Lin, Wensi; Zhang, Jianmei; Ling, Xiaomei; Yu, Ning; Li, Jing; Yang, Haisong; Li, Runtao; Cui, Jingrong

    2013-04-01

    A rapid, simple, and sensitive on-line solid-phase extraction HPLC-DAD method for simultaneous evaluation of the activity of five CYP450 isoforms (CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in vivo has been developed and validated. The five specific probe substrates include caffeine (1A2), metoprolol (2D6), dapsone (3A4), omeprazole (2C19) and chlorzoxazone (2E1). Automated pre-purification of plasma and enrichment of analytes were performed using a C18 on-line solid-phase extraction cartridge. After being eluted from the cartridge, the analytes and the internal standard antipyrine were separated on a C18 RP analytical column and analyzed by DAD. The method was validated to quantify the concentration ranges of 0.05-50.0 μg/ml for dapsone and omeprazole, 0.1-50.0 μg/ml for caffeine and 0.2-50.0 μg/ml for metoprolol and chlorzoxazone. The linearity (R(2)) for all analytes tested was exceeded 0.99. The intra-day precision ranged from 0.29 to 13% and the inter-day precision ranged from 5.0 to 15%, respectively. The intra-day and inter-day accuracy were between 86.7% and 113.6%. The extraction recoveries were in the range 82.8-109.9% for all the analytes and internal standard antipyrine. This method was successfully applied to evaluate the effects of TM208 on rat five CYP450 isoforms.

  2. Synthesis and characterization of pseudo-affinity ligand for penicillin acylase purification.

    Science.gov (United States)

    Keçili, Rüstem; Say, Ridvan; Yavuz, Handan

    2006-11-15

    The aim of this work was to test a chromatographic affinity support containing methacryloyl antipyrine (MAAP) for penicillin acylase (PA) purification by using pure penicillin acylase and crude extract. First, MAAP as a pseudo-specific ligand was synthesized by using methacryloyl chloride and 4-aminoantipyrine. Polymer beads (average size diameter: 40-120 micro m) were prepared by suspension polymerization of ethylene glycol dimethacrylate (EGDMA) and MAAP. This approach for the preparation of adsorbent has several advantages over conventional preparation protocols. An expensive and time consuming step in the preparation of adsorbent is immobilization of a ligand to the adsorption matrix. In this procedure, affinity ligand MAAP acts as comonomer without further modification steps. Poly(EGDMA-MAAP) beads were characterized by FTIR, NMR and screen analysis. Elemental analysis of MAAP for nitrogen was estimated as 89.3 micro mol/g. The prepared adsorbent was then used for the capture of penicillin acylase in batch system. The maximum penicillin acylase adsorption capacity of the poly(EGDMA-MAAP) beads was found to be 82.2 mg/g at pH 5.0. Chromatography with crude feedstock resulted in 23.2-fold purification and 93% recovery with 1.0 M NaOH.

  3. Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

    Directory of Open Access Journals (Sweden)

    P Zakeri-Milani

    2008-09-01

    Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

  4. Disposition kinetics of tylosin tartrate administered intravenously and intramuscularly to normal and water-deprived camels.

    Science.gov (United States)

    Ziv, G; Creveld, C V; Ben-Zvi, Z; Glickman, A; Yagil, R

    1995-08-01

    The disposition kinetics of tylosin tartrate administered intravenously (i.v.) at 10 mg/kg and intramuscularly (i.m.) at 20 mg/kg were studied in normal camels and in the same camels at the end of a 14 day water-deprivation period. After i.v. treatment, serum tylosin concentrations in the water-deprived camels were significantly higher, rate of drug elimination was slower, the volume of distribution was significantly smaller, and total body clearance was significantly slower than in the normal camels. On the other hand, serum drug concentrations were lower in the water deprived camels after i.m. dosing, the mean absorption time was significantly shorter and the i.m. availability was significantly smaller than in the normal camels. Water-deprivation was thought to cause reduced rate of tylosin elimination by the liver, as was shown for antipyrine--a drug which is eliminated from the body exclusively by the liver. Redistribution of tylosin in tissues concomitant with a greater proportion of drug in blood and extracellular fluid of water-deprived camels was suggested as a partial explanation for the higher serum drug levels seen after i.v. dosing. The low i.m. availability observed in the water-deprived camels implies that i.v. is the route of choice for tylosin administration to ill, dehydrated camels.

  5. Some ozone advanced oxidation processes to improve the biological removal of selected pharmaceutical contaminants from urban wastewater.

    Science.gov (United States)

    Espejo, Azahara; Aguinaco, Almudena; Amat, Ana M; Beltrán, Fernando J

    2014-01-01

    Removal of nine pharmaceutical compounds--acetaminophen (AAF), antipyrine (ANT), caffeine (CAF), carbamazepine (CRB), diclofenac (DCF), hydrochlorothiazide (HCT), ketorolac (KET), metoprolol (MET) and sulfamethoxazole (SMX)-spiked in a primary sedimentation effluent of a municipal wastewater has been studied with sequential aerobic biological and ozone advanced oxidation systems. Combinations of ozone, UVA black light and Fe(III) or Fe3O4 constituted the chemical systems. During the biological treatment (hydraulic residence time, HRT = 24 h), only AAF and CAF were completely eliminated, MET, SMX and HCT reached partial removal rates and the rest of compounds were completely refractory. With any ozone advanced oxidation process applied, the remaining pharmaceuticals disappear in less than 10 min. Fe3O4 or Fe(III) photocatalytic ozonation leads to 35% mineralization compared to 13% reached during ozonation alone after about 30-min reaction. Also, biodegradability of the treated wastewater increased 50% in the biological process plus another 150% after the ozonation processes. Both untreated and treated wastewater was non-toxic for Daphnia magna (D. magna) except when Fe(III) was used in photocatalytic ozonation. In this case, toxicity was likely due to the ferryoxalate formed in the process. Kinetic information on ozone processes reveals that pharmaceuticals at concentrations they have in urban wastewater are mainly removed through free radical oxidation.

  6. Chloridazon-catechol dioxygenases, a distinct group of meta-cleaving enzymes.

    Science.gov (United States)

    Schmitt, S; Müller, R; Wegst, W; Lingens, F

    1984-02-01

    We previously described a new meta-cleaving enzyme, termed chloridazon-catechol dioxygenase. The present paper describes the comparison of this enzyme with the meta-cleaving enzymes of eighteen strains of soil bacteria isolated with various aromatic compounds. Four of these strains were isolated with the herbicide chloridazon, six with the analgeticum aminopyrine and one with the analgeticum antipyrine as sole carbon source. These strains all belonged to a new type of bacteria, called Phenylobacteria. The seven other strains were isolated with aromatic compounds such as toluene, 3-phenylpropionate, benzoate, papaverine and 4-chlorobenzoate, and belonged to various species including Pseudomonas, Acinetobacter and Nocardia. In double diffusion experiments with antibodies, prepared against chloridazon-catechol dioxygenase, extracts from the eleven strains of Phenylobacteria gave a cross reaction, whereas the extracts of the seven other strains showed no reaction. The enzymes of the eleven positive strains showed the same characteristic kinetic behaviour as the previously described enzyme. In contrast to catechol 2, 3-dioxygenase they needed the addition of exogenous Fe2+ ions for activity. On ion-exchange chromatography they emerged at the same buffer concentration as chloridazon-catechol dioxygenase. In polyacrylamide electrophoresis they migrated identically. The linkage map derived from the activities of the various enzymes with 10 different substrates revealed an identity of more than 80% for these eleven enzymes. So the meta-cleaving enzymes of the Phenylobacteria seem to form a distinct group among the non-heme iron-containing dioxygenases.

  7. [A new species of the genus Phenylobacterium for the degradation of LAS (linear alkylbenzene sulfonate)].

    Science.gov (United States)

    Ke, Na; Xiao, Changsong; Ying, Qifeng; Ji, Shulan

    2003-02-01

    A strain GZ6 that can biodegrade LAS (Linear Alkylbenzene Sulphonate) is identified. It is aerobic gram-negative rod or short-rod (0.5 to 0.8 by 1.0 to 2.0 Mm). It is mobile with a single polar flagellum. Optimum growth occurred at 30 degrees C and pH7.0. It is catalase positive, urease positive, and arginine decarboxylase positive. All the other physiological and biochemical tests performed were negative. It utilizes the xenobiotic compounds chloridazon, antipyrin and LAS as sole carbon sources. Most sugars, alcohols, and carboxylic acids are not utilized. It has Q-10 as the major quinone. The main cell fatty acids are Sum7, C16:0 and Sum4. The DNA G + C mol % content is 70.10. A phylogenic tree was constructed on the basis of 16S rDNA sequences. It showed that the previously known member of the genus Phenylobacterium, Phenylobacterium mobile DSM1986T, is the nearest neighbor to strain GZ6. The level of binary sequence similarity between them is 97.49%. And the DNA-DNA relatedness is 40%. These genetic analysis and their morphological difference show that they are different species of Phenylobacterium. A new species, Phenylobacterium mobile sp. nov., has been proposed.

  8. Kinetics of gold nanoparticles in the human placenta.

    Science.gov (United States)

    Myllynen, Päivi K; Loughran, Michael J; Howard, C Vyvyan; Sormunen, Raija; Walsh, Adrian A; Vähäkangas, Kirsi H

    2008-10-01

    We studied the transfer of PEGylated gold nanoparticles through perfused human placenta. In 'once-through' perfusions using 15 and 30nm nanoparticles both maternal and fetal outflows were collected. Recirculating perfusions using 10 or 15nm nanoparticles lasted 6h. The gold concentration in samples was analysed on ICP-MS. The reference compound antipyrine crossed the placenta rapidly, as expected. In open perfusions nanoparticles were detected in maternal but not in fetal outflow, suggesting the lack of placental transfer. During 6h re-circulating perfusions, no particles were detected in fetal circulation. Using transmission electron microscopy (TEM) and silver enhancement, nanoparticles could be visualized in the placental tissue mainly in the trophoblastic cell layer. In in vitro experiments, nanoparticles were taken up by BeWo choriocarcinoma cells and retained inside the cells for an extended period of 48h. In conclusion, PEGylated gold nanoparticles of the size 10-30nm did not cross the perfused human placenta in detectable amounts into the fetal circulation within 6h. Whether PEGylated gold nanoparticles eventually are able to cross placenta and whether nanoparticles affect placental functions needs to be further studied.

  9. Feasibility of a 3D human airway epithelial model to study respiratory absorption.

    Science.gov (United States)

    Reus, Astrid A; Maas, Wilfred J M; Jansen, Harm T; Constant, Samuel; Staal, Yvonne C M; van Triel, Jos J; Kuper, C Frieke

    2014-03-01

    The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir™), cultured at the air-liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans.

  10. Comparison Determination of Phenol by High-Performance Liquid Chromatography and Spectrophotometry%高效液相色谱法和光度法测定苯酚的对比

    Institute of Scientific and Technical Information of China (English)

    龙玲; 贾竹贤

    2011-01-01

    The authors analyzed the accuracy and detection limit to determine phenol in 4-amino-antipyrine by spectrophotometry and HPLC. The results showed that the precision and accuracy of both HPLC and spectrophotometry were very high. Spectrophotometry was easy to operate, had a lower limit of detection and lower cost. Spectrophotometry was recommended to determine phenol emission from PF wood products.%分别对液相色谱法和4-氨基安替比林分光光度法,测定苯酚的精密度、检测限及准确度等,进行对比和分析.结果表明:色谱法和光度法精密度和准确度均较高,但光度法操作简便且检出限较低,费用少,建议作为酚醛胶木制品苯酚释放的定量方法.

  11. Microbial degradation of pharmaceuticals in estuarine and coastal seawater

    Energy Technology Data Exchange (ETDEWEB)

    Benotti, Mark J. [Marine Sciences Research Center, Stony Brook University, Stony Brook, NY 11794-5000 (United States); Brownawell, Bruce J. [Marine Sciences Research Center, Stony Brook University, Stony Brook, NY 11794-5000 (United States)], E-mail: bruce.brownawell@sunysb.edu

    2009-03-15

    Microbial degradation rates were measured for 19 pharmaceuticals in estuarine and coastal surface water samples. Antipyrine, carbamazepine, cotinine, sulfamethoxazole, and trimethoprim were the most refractory (half-lives, t{sub 1/2} = 35 to >100 days), making them excellent candidates for wastewater tracers. Nicotine, acetaminophen, and fluoxetine were labile across all treatments (t{sub 1/2} = 0.68-11 days). Caffeine, diltiazem, and nifedipine were also and relatively labile in all but one of the treatments (t{sub 1/2} = 3.5-13 days). Microbial degradation of caffeine was further confirmed by production {sup 14}CO{sub 2}. The fastest decay of non-refractory compounds was always observed in more sewage-affected Jamaica Bay waters. Degradation rates for the majority of these pharmaceuticals are much slower than reported rates for small biomolecules, such as glucose and amino acids. Batch sorption experiments indicate that removal of these soluble pharmaceuticals from the water column to sediments is a relatively insignificant removal process in these receiving waters. - Microbial degradation rates were measured for 19 structurally variable pharmaceuticals in wastewater-impacted estuarine and coastal seawater.

  12. Structure-based modelling in reproductive toxicology: (Q)SARs for the placental barrier.

    Science.gov (United States)

    Hewitt, M; Madden, J C; Rowe, P H; Cronin, M T D

    2007-01-01

    The replacement of animal testing for endpoints such as reproductive toxicity is a long-term goal. This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental barrier, then it will not be a reproductive toxicant. Such a model could be placed at the start of any integrated testing strategy. To develop these models the literature was reviewed to obtain data relating to the transfer of molecules across the placenta. A reasonable number of data were obtained and are suitable for the modelling of the ability of a molecule to cross the placenta. Clearance or transfer indices data were sought due to their ability to eliminate inter-placental variation by standardising drug clearance to the reference compound antipyrine. Modelling of the permeability data indicates that (Q)SARs with reasonable statistical fit can be developed for the ability of molecules to cross the placental barrier membrane. Analysis of the models indicates that molecular size, hydrophobicity and hydrogen-bonding ability are molecular properties that may govern the ability of a molecule to cross the placental barrier.

  13. Molecular docking and fluorescence characterization of benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives, a novel class of selective cyclooxygenase-2 inhibitors.

    Science.gov (United States)

    Barone, Mariarita; Pannuzzo, Giovanna; Santagati, Andrea; Catalfo, Alfio; De Guidi, Guido; Cardile, Venera

    2014-05-14

    The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 1-11; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX)-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = -9.4) and good fluorescent properties (Φfl = 0.032). Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis.

  14. Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Mariarita Barone

    2014-05-01

    Full Text Available The aims of this study were: (i to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 1–11; and (ii to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = −9.4 and good fluorescent properties (Φfl = 0.032. Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis.

  15. Death of an infant involving benzocaine.

    Science.gov (United States)

    Logan, Barry K; Gordon, Ann Marie

    2005-11-01

    This report describes the death of a four-month-old Hispanic male which may be related to benzocaine toxicity. A toxicological evaluation revealed benzocaine at a concentration of 3.48 mg/L, and postmortem methemoglobin of 36% (normal 0.4-1.5). Methemoglobinemia is a complication of benzocaine toxicity. In light of the toxicology findings, the coroner investigated the source of the benzocaine and discovered that the child was treated with Zenith Goldline Allergen Ear Drops containing 0.25% w/v benzocaine and 5.4% w/v antipyrine. There was an admission by a caregiver that on the day prior to the child's death, he had been treated with three times the prescribed dose. Blood benzocaine concentrations in nine other unrelated cases were determined and concentrations ranged from benzocaine positive cases ranged from 6-69%; however, methemoglobin concentrations in postmortem cases are frequently elevated and should be interpreted with caution. The unknown significance of the benzocaine, and the circumstances of the case raise questions about the ultimate attribution of this death to SIDS.

  16. A fundamental study of the impact of pressure on the adsorption mechanism in reversed-phase liquid chromatography.

    Science.gov (United States)

    Åsberg, Dennis; Samuelsson, Jörgen; Fornstedt, Torgny

    2016-07-29

    A fundamental investigation of the pressure effect on individual adsorption sites was undertaken based on adsorption energy distribution and adsorption isotherm measurements. For this purpose, we measured adsorption equilibrium data at pressures ranging from 100 to 1000bar at constant flow and over a wide concentration range for three low-molecular-weight solutes, antipyrine, sodium 2-naphthalenesulfonate, and benzyltriethylammonium chloride, on an Eternity C18 stationary phase. The adsorption energy distribution was bimodal for all solutes, remaining clearly so at all pressures. The bi-Langmuir model best described the adsorption in these systems and two types of adsorption sites were identified, one with a low and another with a high energy of interaction. Evidence exists that the low-energy interactions occur at the interface between the mobile and stationary phases and that the high-energy interactions occur nearer the silica surface, deeper in the C18 layer. The contribution of each type of adsorption site to the retention factor was calculated and the change in solute molar volume from the mobile to stationary phase during the adsorption process was estimated for each type of site. The change in solute molar volume was 2-4 times larger at the high-energy site, likely because of the greater loss of solute solvation layer when penetrating deeper into the C18 layer. The association equilibrium constant increased with increasing pressure while the saturation capacity of the low-energy site remained almost unchanged. The observed increase in saturation capacity for the high-energy site did not affect the column loading capacity, which was almost identical at 50- and 950-bar pressure drops over the column.

  17. Pulmonary uptake of morphine (M)

    Energy Technology Data Exchange (ETDEWEB)

    Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.; Dawson, C.A.; Kampine, J.P.

    1986-03-01

    Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium within 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.

  18. Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt Extrusion and Film Coating.

    Science.gov (United States)

    Jedinger, Nicole; Schrank, Simone; Fischer, Johannes M; Breinhälter, Karlheinz; Khinast, Johannes; Roblegg, Eva

    2016-02-01

    This study focused on the development of flexible (i.e., deformable) multiple-unit pellets that feature (i) a prolonged drug release, (ii) drug abuse deterrence, and (iii) a minimal risk of alcohol-induced dose dumping (ADD). Deformable pellets were prepared via an advanced continuous one-step hot-melt extrusion (HME) technique, with the drug (i.e., antipyrine and codeine phosphate) fed as an aqueous solution into the molten matrix material (i.e., cornstarch, gum arabic, and xanthan). Formulations that had suitable mechanical characteristics (i.e., high compression strength) were coated with a flexible Aquacoat(®) ARC film to ensure prolonged release and to avoid ADD. The pellets were characterized in terms of their mechanical properties and in vitro drug release behavior in alcoholic media. All formulations were abuse deterrent: they had a high compression strength and grinding the pellets into powder was impossible. Since the pellets comprising gum arabic and xanthan as a matrix did not remain intact during dissolution testing, they had a very fast drug release rate. Cornstarch-based pellets that swelled but remained intact in the dissolution media had a slower drug release. Coated cornstarch-based pellets had a prolonged release over 8 h and resistance to dose dumping in 20 and 40% ethanol. Our results indicate that cornstarch-based pellets manufactured via the advanced HME process followed by coating are a promising formulation that makes tampering difficult due to a high compression strength combined with robustness in alcoholic media.

  19. An Automated High-Throughput Metabolic Stability Assay Using an Integrated High-Resolution Accurate Mass Method and Automated Data Analysis Software

    Science.gov (United States)

    Shah, Pranav; Kerns, Edward; Nguyen, Dac-Trung; Obach, R. Scott; Wang, Amy Q.; Zakharov, Alexey; McKew, John; Simeonov, Anton; Hop, Cornelis E. C. A.

    2016-01-01

    Advancement of in silico tools would be enabled by the availability of data for metabolic reaction rates and intrinsic clearance (CLint) of a diverse compound structure data set by specific metabolic enzymes. Our goal is to measure CLint for a large set of compounds with each major human cytochrome P450 (P450) isozyme. To achieve our goal, it is of utmost importance to develop an automated, robust, sensitive, high-throughput metabolic stability assay that can efficiently handle a large volume of compound sets. The substrate depletion method [in vitro half-life (t1/2) method] was chosen to determine CLint. The assay (384-well format) consisted of three parts: 1) a robotic system for incubation and sample cleanup; 2) two different integrated, ultraperformance liquid chromatography/mass spectrometry (UPLC/MS) platforms to determine the percent remaining of parent compound, and 3) an automated data analysis system. The CYP3A4 assay was evaluated using two long t1/2 compounds, carbamazepine and antipyrine (t1/2 > 30 minutes); one moderate t1/2 compound, ketoconazole (10 < t1/2 < 30 minutes); and two short t1/2 compounds, loperamide and buspirone (t½ < 10 minutes). Interday and intraday precision and accuracy of the assay were within acceptable range (∼12%) for the linear range observed. Using this assay, CYP3A4 CLint and t1/2 values for more than 3000 compounds were measured. This high-throughput, automated, and robust assay allows for rapid metabolic stability screening of large compound sets and enables advanced computational modeling for individual human P450 isozymes. PMID:27417180

  20. Phenylobacterium muchangponense sp. nov., isolated from beach soil, and emended description of the genus Phenylobacterium.

    Science.gov (United States)

    Oh, Yong-Sik; Roh, Dong-Hyun

    2012-04-01

    A Gram-staining-negative, non-motile, aerobic bacterium, designated strain A8T, was isolated from the beach soil of Muchangpo, Korea. Cells were rod-shaped (0.5-0.6×0.7-1.3 µm) and colonies were colourless, circular with entire edges and had a glistening surface. The isolate grew optimally at 25-35 °C and did not require NaCl for growth. Strain A8T could not assimilate acetate, DL-lactate, succinate, antipyrine or chloridazon, but weakly assimilated L-phenylalanine. Major fatty acids were summed feature 7 (comprising C18:1ω7c/ω9t/ω12t), C16:0 and summed feature 4 (comprising C16:1ω7c/ iso-C15:0 2-OH). The major isoprenoid quinone was ubiquinone-10 and the DNA G+C content was 72.3 mol%. Comparative 16S rRNA gene sequence studies showed that strain A8T belonged to the family Caulobacteraceae, class Alphaproteobacteria and was most closely related to type strains of members of the genus Phenylobacterium (95.7-97.1 % similarity). Signature nucleotides and phylogenetic analysis of the 16S rRNA gene sequence also suggested that strain A8T was affiliated with the genus Phenylobacterium. Low DNA-DNA relatedness values (3.0±1.8-11.5±3.2 %) indicated that strain A8T represented a distinct species that was separated from other type strains in the genus Phenylobacterium. On the basis of evidence from a polyphasic study, it is proposed that strain A8T (=KACC 15042T=LMG 25973T) represents the type strain of a novel species, Phenylobacterium muchangponense sp. nov. An emended description of the genus Phenylobacterium is also presented.

  1. « Destruction de la langue » dans la première œuvre Dada : des impertinences lexicales à la théâtralité

    Directory of Open Access Journals (Sweden)

    Kunešová Mariana

    2015-12-01

    Full Text Available The paper deals with the issue of signification in Dada creation which is well known for its goal of « abolition of logic », and its literary consequence: structures not respecting the speech acts to the point that they seem to destroy the very possibility of presence of acceptable significations. The author of the paper, suggesting to name these rebel structures « motivation attacks », starts her research from the famous interpretation of Dada activity by Jacques Rivière : « It is impossible for a man to say something that has no meaning » (La Nouvelle Revue Française, 1920, and puts out these main questions: What can be the concrete impact of motivation attacks? To which acceptable significations can they lead? Can these have a different form than the one of general connotations of chaos or aggression? The corpus of the research is La Première aventure céleste de Monsieur Antipyrine by Tristan Tzara – the legendary first literary Dada opus, being nevertheless little known itself. The choice of the text is due also to its specific genre: written in a theatrical form, this « collage » is likely to have no other characteristics of scenicity and thus to be theatrically nonoperational. However, the signification, precisely, is a potential means capable of ensuring the attention of the public during the performance. Thus, an analysis of signification should also contribute to clarifying the question of the theatrical potential of La Première aventure.

  2. Virtual Experiments Enable Exploring and Challenging Explanatory Mechanisms of Immune-Mediated P450 Down-Regulation.

    Directory of Open Access Journals (Sweden)

    Brenden K Petersen

    Full Text Available Hepatic cytochrome P450 levels are down-regulated during inflammatory disease states, which can cause changes in downstream drug metabolism and hepatotoxicity. Long-term, we seek sufficient new insight into P450-regulating mechanisms to correctly anticipate how an individual's P450 expressions will respond when health and/or therapeutic interventions change. To date, improving explanatory mechanistic insight relies on knowledge gleaned from in vitro, in vivo, and clinical experiments augmented by case reports. We are working to improve that reality by developing means to undertake scientifically useful virtual experiments. So doing requires translating an accepted theory of immune system influence on P450 regulation into a computational model, and then challenging the model via in silico experiments. We build upon two existing agent-based models-an in silico hepatocyte culture and an in silico liver-capable of exploring and challenging concrete mechanistic hypotheses. We instantiate an in silico version of this hypothesis: in response to lipopolysaccharide, Kupffer cells down-regulate hepatic P450 levels via inflammatory cytokines, thus leading to a reduction in metabolic capacity. We achieve multiple in vitro and in vivo validation targets gathered from five wet-lab experiments, including a lipopolysaccharide-cytokine dose-response curve, time-course P450 down-regulation, and changes in several different measures of drug clearance spanning three drugs: acetaminophen, antipyrine, and chlorzoxazone. Along the way to achieving validation targets, various aspects of each model are falsified and subsequently refined. This iterative process of falsification-refinement-validation leads to biomimetic yet parsimonious mechanisms, which can provide explanatory insight into how, where, and when various features are generated. We argue that as models such as these are incrementally improved through multiple rounds of mechanistic falsification and

  3. Upconversion ratiometric fluorescence and colorimetric dual-readout assay for uric acid.

    Science.gov (United States)

    Fang, Aijin; Wu, Qiongqiong; Lu, Qiujun; Chen, Hongyu; Li, Haitao; Liu, Meiling; Zhang, Youyu; Yao, Shouzhuo

    2016-12-15

    A new upconversion colorimetric and ratiometric fluorescence detection method for uric acid (UA) has been designed. Yb(3+), Er(3+) and Tm(3+) co-doped NaYF4 nanoparticles (UCNPs) was synthesized. The co-doped NaYF4 nanoparticles, emit upconversion fluorescence with four typical emission peaks centered at 490nm, 557nm, 670nm and 705nm under the 980nm near-infrared (NIR) irradiation. The ZnFe2O4 magnetic nanoparticles (MNPs) possessing excellent peroxidase-like activity was prepared and used to catalyze oxidation the coupling of N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt (TOPS) and 4-amino-antipyrine (4-AAP) in the presence of H2O2 to form purple products (compound 1) which has a characteristic absorption peak located at 550nm. The upconversion fluorescence at 557nm was quenched by the compound 1 while the upconversion emission at 705nm was essentially unchanged, the fluorescence ratio ((I557/I705)0/(I557/I705)) is positively proportional to UA concentration in existence of uricase. More importantly, colorimetric signal can be easily observed and applied to directly distinguish the concentration of UA by the naked eye. Under the optimized conditions, the linear range of colorimetric and ratiometric fluorescence sensing towards UA was 0.01-1mM, the detection limits were as low as 5.79μM and 2.86μM (S/N=3), respectively. The proposed method has been successfully applied to the analysis of UA in human serum. These results indicate that the colorimetric and ratiometric fluorescence dual-readout assay method has great potential for applications in physiological and pathological diagnosis.

  4. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

  5. Effect of operating conditions in soil aquifer treatment on the removals of pharmaceuticals and personal care products

    Energy Technology Data Exchange (ETDEWEB)

    He, Kai, E-mail: hekai@urban.env.kyoto-u.ac.jp; Echigo, Shinya; Itoh, Sadahiko

    2016-09-15

    Soil aquifer treatment (SAT) is an alternative advanced treatment for wastewater reclamation, and it has the potential to control micropollutants including pharmaceuticals and personal care products (PPCPs). However, the relationship of operating conditions in SAT and removals of micropollutants was not clear. In this study, the effects of operating conditions on the removals of PPCPs were evaluated by using lab-scale columns and plant pilot-scale reactors under different operating conditions. Firstly, weathered granite soil (WGS), standard sand (SAND) and Toyoura standard sand (TS) have different soil characteristics such as total organic carbon (TOC) and cation exchange capacity (CEC). In the columns with these packing materials, the removals of carboxylic analgesics and antilipidemics were effective regardless packing materials. The removals of antibiotics were more effective in WGS than in TS and SAND, indicating high TOC and CEC enhance the sorption in SAT. Secondly, with the extension of hydraulic retention time (HRT), the removals of sulfamethoxazole, acetaminophen, crotamiton, and antipyrine were improved in WGS columns, and adaptable biodegradation for moderately removable PPCPs was formed. Thirdly, the removal efficiencies of sulfamethoxazole and crotamiton were higher in the WGS column under vadose condition than in the WGS column under saturated condition, because of aerobic condition in WGS column under vadose condition. Though long HRT and vadose condition had positive influence on the removals of several PPCPs such as sulfamethoxazole, WGS column with an HRT of 7 days under saturated condition removed most PPCPs. - Highlights: • Soil organic matter and cation exchange capacity enhanced the removals of antibiotics in SAT. • A hydraulic retention time (HRT) of 7 days was sufficient for the removals of most PPCPs. • The removals of most selected PPCPs were similar under vadose and saturated conditions. • Vadose condition contributed to the

  6. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Levy, D E; Duffy, T E

    1982-05-01

    Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.

  7. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori.

    Science.gov (United States)

    Ziebarth, D; Spiegelhalder, B; Bartsch, H

    1997-02-01

    Micro-organisms commonly present in human saliva and three DSM strains (Helicobacter pylori, Campylobacter jejuni and Neisseria cinerea), which can be isolated from the human gastro-intestinal tract, were assayed in vitro for their capacity to catalyse N-nitrosation of a series of medicinal drugs and other compounds. Following incubation at pH 7.2 in the presence of nitrate (or nitrite) for up to 24 (48) h, the yield of N-nitroso compounds (NOC) was quantified by HPLC equipped with a post-column derivatization device, allowing the sensitive detection of acid-labile and acid-stable NOC. Eleven out of the 23 test compounds underwent bacteria-catalysed nitrosation by salivary bacteria, the yield of the respective nitrosation products varying 800-fold. 4-(Methylamino)antipyrine exhibited the highest rate of nitrosation, followed by dichlofenac > metamizole > piperazine > five other drugs, whilst L-proline and L-thioproline had the lowest nitrosation rate. Ten drugs including aminophenazone, cimetidine and nicotine, did not inhibit bacterial growth, allowing transitory nitrite to be formed, but no N-nitroso derivatives were detected. Three drugs inhibited the proliferation of bacteria and neither nitrite nor any NOC were formed. Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7.2. As compared to Neisseria cinerea used as a nitrosation-proficient control strain, H. pylori was 30-100 times less effective, whilst C. jejuni had intermediary activity. The results of our sensitive nitrosation assay further confirm that bacteria isolated from human sources, possessing nitrate reductase and/or nitrosating enzymes such as cytochrome cd1-nitrite reductase (Calmels et al., Carcinogenesis, 17, 533-536, 1996), can contribute to intragastric nitrosamine formation in the anacidic stomach when nitrosatable precursors from exogenous and endogenous sources

  8. Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

    Directory of Open Access Journals (Sweden)

    A.M. Vinagre

    2009-11-01

    Full Text Available Dipyrone (Dp, 4-aminoantipyrine (AA and antipyrine (At administered iv and Dp administered icv delay gastric emptying (GE in rats. The participation of capsaicin (Cps-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g. Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg, or saline; or treated icv with Dp (4 μmol/animal or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8 in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2%, respectively did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8% and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3%, respectively. The effect of icv administration of Dp (N = 6 was not modified by pretreatment with Cps (63.3 ± 5.7% compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4%. The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

  9. Novel transdermal drug penetration enhancer: synthesis and enhancing effect of alkyldisiloxane compounds containing glucopyranosyl group.

    Science.gov (United States)

    Akimoto, Tomoko; Nagase, Yu

    2003-03-01

    The syntheses of alkyldisiloxanes containing sugar moiety with various alkyl chain length were investigated, in order to develop a silicone-based transdermal penetration enhancer which was expected to show a low irritation to the skin. 1-Alkyl-3-beta-D-glucopyranosyl-1,1,3,3-tetramethyldisiloxanes (Glc-SiCs) were prepared by two-step hydrosilylations of 1-alkene and 1-allyl-beta-D-glucose tetraacetate with 1,1,3,3-tetramethyldisiloxane in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect of Glc-SiCs on the percutaneous drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine (ANP) and indomethacin (IND) were used as hydrophilic and hydrophobic model drugs, respectively, and the amount of drug permeating through the rat abdominal skin with or without Glc-SiCs was estimated by HPLC. As a result, Glc-SiCs exhibited a enhancing effect on the permeation of both drugs through the skin, which was influenced by the alkyl chain length of Glc-SiCs. In addition, it was suggested that a suitable balance of polarity would be necessary to appear the high enhancing effect, where Glc-SiCs with octyl and decyl groups exhibited the highest enhancing effect. From the determination of kinetic parameters in the drug permeation, it was also found that this enhancing effect was due to the increase of both partition and diffusion coefficients of drug permeation through the skin. By experiments to determine the amount of cholesterol extracted from the skin, the defatting effect would be one of the functions of Glc-SiCs which resulted in the high enhancing activity. Furthermore, according to the Draize test, it was confirmed that Glc-SiCs showed a low irritation to the skin.

  10. Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China.

    Science.gov (United States)

    Cai, Mei-Quan; Wang, Rong; Feng, Li; Zhang, Li-Qiu

    2015-02-01

    A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.

  11. CYP450-dependent biotransformation of the insecticide fipronil into fipronil sulfone can mediate fipronil-induced thyroid disruption in rats.

    Science.gov (United States)

    Roques, Béatrice B; Lacroix, Marlène Z; Puel, Sylvie; Gayrard, Véronique; Picard-Hagen, Nicole; Jouanin, Isabelle; Perdu, Elisabeth; Martin, Pascal G; Viguié, Catherine

    2012-05-01

    In rats, the widely used insecticide fipronil increases the clearance of thyroxine (T(4)). This effect is associated with a high plasma concentration of fipronil sulfone, the fipronil main metabolite in several species including rats and humans. In sheep, following fipronil treatment, fipronil sulfone plasma concentration and thyroid disruption are much lower than in rats. We postulated that fipronil biotransformation into fipronil sulfone by hepatic cytochromes P450 (CYP) could act as a potential thyroid disruptor. The aim of this study was to determine if fipronil sulfone treatment could reproduce the fipronil treatment effects on T(4) clearance and CYP induction in rats. Fipronil and fipronil sulfone treatments (3.4 μmol/kg/day per os, 14 days) increased total and free T(4) clearances to the same extent in THX + T(3), euthyroid-like rats. Both treatments induced a 2.5-fold increase in Ugt1a1 and Sult1b1 messenger RNA (mRNA) expressions and a twofold increase in UGT1A activity suggesting that T(4) elimination was mediated, at least in part, by hepatic uridine 5'-diphospho-glucuronosyltransferases (UGT) and/or sulfotransferases (SULT) induction. Both treatments induced a 10-fold increase in Cyp3a1 and Cyp2b2 mRNA expressions concomitant with a threefold increase in CYP3A immunoreactivity and a 1.7-fold increase in antipyrine clearance, a biomarker of CYP3A activity. All these results showed that fipronil sulfone treatment could reproduce the fipronil treatment effects on T(4) clearance and hepatic enzyme induction in rats. The potential of fipronil sulfone to act as a thyroid disruptor is all the more critical because it persists much longer in the organism than fipronil itself.

  12. Regulation of drug metabolism in man by environmental chemicals and diet

    Energy Technology Data Exchange (ETDEWEB)

    Conney, A.H. (Hoffmann-LaRoche Inc., Nutley, NJ); Pantuck, E.J.; Hsiao, K.C.; Kuntzman, R.; Alvares, A.P.; Kappas, A.

    1977-04-01

    Studies in animals have shown that many environmental pollutants induce the synthesis or inhibit the activity of microsomal mixed-function oxygenases that metabolize drugs, carcinogens and normal body constituents such as steroid hormones. These effects on microsomal enzyme activity alter the duration and intensity of action of foreign and endogenous chemicals in animals, and such effects on metabolism may influence the carcinogenicity of some pollutants in man. Studies on the effects of environmental chemicals on drug metabolism in man are sparse. Exposure of humans to DDT or lindane in a pesticide factory results in an enhanced rate of metabolism of antipyrine and phenylbutazone and an increased urinary excretion of 6-..beta..-hydroxycortisol. Polycyclic aromatic hydrocarbons present in cigarette smoke, in charcoal-broiled meats, and in polluted city air are potent inducers of drug-metabolizing enzymes in animals. In humans, cigarette smoking stimulates the activity of placental enzymes that metabolize several drugs and carcinogens. In addition, cigarette smokers metabolize phenacetin, theophylline, and other drugs more rapidly in vivo than nonsmokers. Dietary factors are important in the regulation of drug metabolism in animals and man. Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man. It is likely that polycyclic aromatic hydrocarbons are the major inducers in charcoal-broiled beef.

  13. Regional cerebral blood flow during hypoxia-ischemia in immature rats

    Energy Technology Data Exchange (ETDEWEB)

    Vannucci, R.C.; Lyons, D.T.; Vasta, F.

    1988-02-01

    Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O2 at 37 degrees C. Before and during hypoxia, the rat pups received an injection of iodo(/sup 14/C)antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxia-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15, 17, 34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors may influence the heterogeneous pattern of damage seen within individual structures.

  14. 一个可降解直链烷基苯磺酸盐的新种%A New Species of the Genus Phenylobacterium for the Degradation of LAS (Linear Alkylbenzene Sulfonate)

    Institute of Scientific and Technical Information of China (English)

    柯娜; 肖昌松; 应启锋; 纪树兰

    2003-01-01

    本文鉴定了一株可完全降解直链烷基苯磺酸盐(Linear Alkylbenzene Sulphonate,简称LAS)的菌株GZ6.革兰氏染色阴性,细胞为杆状或短杆状,大小为0.5μm~0.8 μm×1.0μm~2.0 μm,其生长pH范围为pH6.0~10.0,最适生长pH为7.0,生长温度范围为4℃~40℃,最适生长温度为30℃.生化特征测定除过氧化氢酶、尿酶、精氨酸脱羧酶反应为阳性,其它均为阴性.可利用Chloridazon、安替比林(antipyrin)以及LAS等为碳源.不能利用大多数糖醇.醌组分以泛醌Q-10为主.菌体脂肪酸主要为C18∶1、C16∶0及C16∶1.DNA中G+C mol%含量为70.10.16S rRNA 序列分析表明菌株GZ6 与其亲缘关系最近的菌株Phenylobacterium immobile DSM1986T序列相似值为97.49%,DNA-DNA杂交率为40%.菌株GZ6具极生鞭毛,可运动,两者在细胞形态有很大差异.故将菌株GZ6定为苯基杆菌属的新种可动苯基杆菌(Phenylobaterium mobile) GZ6.

  15. Synthesis of a New Triazene Reagent and Its Application to the Color Reaction with Gold( Ⅲ ) Ion%一种新的三氮烯试剂的合成并应用于金(Ⅲ)离子的显色反应

    Institute of Scientific and Technical Information of China (English)

    陈文宾; 郑秋霞; 马卫兴; 许兴友

    2011-01-01

    以4-氨基安替比林和对氨基苯磺酸为主要反应物,制备了1-(4-安替比林)-3-(对苯磺酸)三氮烯(ASTA).采用红外光谱法对ASTA的分子组成及结构作了检测.研究了该试剂与金(Ⅲ)的显色反应.在含有Triton X-100的pH 10.3的硼砂-氢氧化钠缓冲溶液中,ASTA与金(Ⅲ)反应生成配合比为2:1的橙红色配合物,在其最大吸收波长496nm处的表观摩尔吸光率为1.8×105L·mol-1·cm-1.金(Ⅲ)的质量浓度在0.06~1.05mg·L-1,范围内与其吸光度呈线性关系,方法的检出限(3S/N)为0.02mg·L-1.方法用于含金矿样品中金(Ⅲ)的测定,结果与原子吸收光谱法相一致,方法的回收率在109.0%~118.2%之间,相对标准偏差(n=6)小于4.0%.%A new reagent, 1-(4-antipyrinyl)-3-(sulfanilic acid)-triazene (ASTA), was synthesized by the reaction between 4-antipyrine and sulfanilic acid. Molecular composition and structure of ASTA were determined by FT-IRS. It was found that in a Na2B4O7-NaOH buffer medium of pH 10. 3 containing Triton X-100, a stable coordination complex (R: Au3+ =2 : 1) was formed by the reaction of ASTA with gold ion, having the absorption maximum at 496 nm. Linear relationship between values of absorbanee and concentration of Au (Ⅲ) ion was obtained in the range of 0.06-1.05 mg·L-1. Detection limit (3S/N) found was 0. 02 mg· L-1 The apparent molar absorptivity of the color system was found to be 1.8 × 105L · mol-1 · cm-1. The proposed method was applied to the determination of Au(Ⅲ) in gold ore samples, and the results obtained were in consistency with those obtained by AAS. Values of recovery were found in the range of 109.0%-118. 2% and RSD (n=6) was less than 4.0%.

  16. 血清尿素丙酮酸氧化酶测定新方法的研究及应用%A new assay method for serum urea determination with pyruvate oxidase and its application

    Institute of Scientific and Technical Information of China (English)

    唐先平; 秦媛媛; 宋蓉; 马文军

    2008-01-01

    目的 建立一种血清尿素测定的新方法和临床应用.方法 应用脲酶、丙酮酸氧化酶、丙酮酸激酶与色原系统2,4-二氯苯酚、4-氨基安替比林,进行血清尿素浓度的酶法测定.结果 磷酸盐缓冲液最适浓度为50 mmol、pH7.2,最大吸收峰为510 nm,线性范围为0~42 mmol/L,显色稳定.精密度:批内(n=20)CV为1.89%~3.21%,批间(n=20)CV为1.96%~3.45%,回收率为96.2%~104.2%,平均回收率为99.5%.与酶偶联速率法比较,相关系数r=0.995,回归方程Y=1.023x+0.38,两法高度相关,正常参考值范围为儿童组2.20~8.50 mmol/L,少年组2.60~8.60 mmol/L,成人组2.85%~8.95 mmol/L.结论 本法具有高度的特异性和准确性,其操作简便、灵敏快速、标本用量少、结果稳定,适用于全自动、半自动生化分析仪,更适用于中小医院,有较大的推广使用价值.%Objective To establish a new assay method for serum urea determination, and ex-plore its clinical application. Methods Urease, pyruvate oxidase, pyruvate kinase and aniline pigment system 2,4-dichlorophenol, and 4-amino-antipyrine were applying in enzymic method assay for serum urea. Results The optimal concentration of phosphate buffer was 50 retool, pH value was 7.2, maxi-mum absorption peak was at 510 nm, and the linearity range was 0-42 mmol/L;precisicn: within-run(n=20) CV= 1.89 %-3. 21% and between-run (n=20) CV=1.96 %-3.45 % ;the recovery rate was 96.2%-104.2%, with an average of 99. 5%. As compared with enzyme coupled rate method, the co-efficient correlation was 0.995, regression equation was Y= 1.023x+0. 38, and the two methods were highly correlated. Normal reference value range was 2.2-8.5 mmol/L in children group, 2.6-8.6mmol/L in juvenile group, and 2.85-8.95 mmol/L in adult group. Conclusion The new assay method is simple, sensitive, rapid and result stable with high specificity and accuracy, which is applicable in complete automatic, semi-automatic biochemical analysis instrument. It

  17. Analysis of the photo catalytic degradation of the 4-chloro phenol and endosulfan by gas chromatography; Analisis de la degradacion fotocatalitica del 4-clorofenol y endosulfan por cromatografia de gases

    Energy Technology Data Exchange (ETDEWEB)

    Pichardo S, E. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    maximum degradation percentage of 87.87, 62.49, 52.56 and 35.75 to these concentrations and of the same way by ultraviolet-visible, was obtained: 91.6, 61.5, 50.64 and 37.71 degradation percentage respectively, showing that the results correspond in both techniques. As soon as refers to the endosulfan didn't register results of ultraviolet-visible spectroscopy since it was not possible to determine it by the amine 4-antipyrine method. On the other hand, by means of gas chromatography they didn't register results of the quantitative analysis of the endosulfan because they were not observed results during the analysis. An explanation was that the endosulfan was adsorbed in TiO{sub 2} surface, to be able to corroborate this, the samples were analyzed by the Total Organic Carbon technique (COT). At the end of the work it is made an analysis and discussion of the results of the 4-chloro phenol, where the two used control techniques are compared. (Author)

  18. LC-MS/MS Method in Determination of Meropenem Concentration of Microdialysis Samples of Rats%建立液相色谱-质谱串联法测定大鼠微透析样品中美罗培南的浓度

    Institute of Scientific and Technical Information of China (English)

    彭珑; 王丹; 吴诚; 周静超; 郭明星; 童卫杭

    2015-01-01

    Objective To establish a high performance liquid chromatography-tandem mass spectrometry ( LC-MS/MS) method to monitor real-time concentration changes of Meropenem during microdialysis samples of rats so as to provide the foundation for further pharmacokinetic/pharmacodynamic ( PK/PD) study of Meropenem on infected tissues with microdialysis technique. Methods Chromatographic separation was performed on a COSMOSIL 5C18-PAQ (150 mm × 4. 6 mm, 5μm) column by a gradient elution, the mobile phase was composed of acetonitrile and-0. 1% for-mic acid aqueous solution at a 1. 0 mL/min flow rate in a run time of 8 min. The quantification of Meropenem and internal standard ( Antipyrine) were determined by multiple reaction monitoring ( MRM) mode with a positive electrospray ioniza-tion (ESI), and the ion transitions were m/z 384. 2→141. 2 and m/z 189. 2→104. 0 for Meropenem and internal stand-ard respectively. Results The Meropenem showed good linear correlation in a range of 0. 01-40 μg/mL (r=0. 9979). The intra- and inter-day precisions [ relative standard deviation ( RSD) %] were all within 9. 76%, and accuracy (RE%) ranged from -7. 87% to 0. 28%. Conclusion The established LC-MS/MS method of Meropenem is accurate with good sensitivity, specificity and precision, which can be applied in quick and effective analysis of Meropenem con-centration in microdialysis samples.%目的 建立高效液相色谱-质谱串联法( HPLC-MS/MS)用于监测微美罗培南在透析液中实时变化的浓度,为应用微透析技术对感染靶部位美罗培南的药动/药效学研究奠定基础. 方法 采用COSMOSIL 5C18-PAQ (150 mm × 4. 6 mm, 5 μm)色谱柱进行分离,流动相为乙腈-0. 1%甲酸水,梯度洗脱,流速1. 0 ml/min,分析时间为8 min;美罗培南和内标(安替比林)均在ESI正离子模式扫描,以多反应监测( MRM)模式进行扫描,检测离子对美罗培南m/z 384. 2→141. 2,内标m/z 189. 2→104. 0. 结果 美罗培南在0. 01~40 μg/ml线

  19. LC - MS/MS determination of 23 nonsteroidal anti - inflammatory drugs in traditional Chinese medicine preparation%LC-MS/MS法测定中成药制剂中23个非甾体抗炎药

    Institute of Scientific and Technical Information of China (English)

    潘炜; 顾鑫荣; 刘志璋; 胡侠

    2012-01-01

    目的:建立了一种液相色谱串联四极杆质谱分析方法,对治疗风湿和类风湿的中成药制剂中的23个非甾体抗炎药进行快速筛查、定性识别和准确定量.方法:添加在中成药中的对乙酰氨基酚、乙酰水杨酸、安乃近、安替比林、洛索洛芬钠、氨基比林、吡罗昔康、萘普生、舒林酸、美洛昔康、氯唑沙宗、芬布芬、布洛芬、双氯芬酸、吲哚美辛、贝诺脂、尼美舒利、塞来昔布、醋氯芬酸、奥沙普秦、萘丁美酮、甲酚那酸、酮洛芬等23西药成分用80%甲醇提取,醋酸铵水溶液-甲醇梯度于ACQUITY UPLC BEH C18色谱柱分离,串联四级杆质谱仪检测,MRM方式采集并定量.结果:23个药物质谱检测的线性范围宽,相关性好,r2≥0.9901;方法精密度以6次测定值的RSD表示,为2.1%~7.7%;方法回收率用2个浓度(0.05,1.0mg·g-1)进行添加实验,较高浓度时的回收率范围在94.2%~110%;最低定量限(LLOQ)规定为添加回收实验中S/N≥10时的最低添加浓度,23个药物的LLOQ为0.0013 ~0.05 μg·g-1.结论:本法可用于中成药制剂中多组分解热镇痛药和非甾体抗炎药的同时定量测定.%Objective: To develop a highly selective LC - MS/MS method using a tandem quadrupole mass spectrometer detector for rapidly screening, qualitative identifying and accurate quantifying of 23 nonsteroidal anti - inflammatory (NSAIDs) added in the traditional Chinese medicine preparations. Methods: Acetaminophen, aspirin, metamizole, antipyrine, loxoprofen, antondine, piroxicam, naproxen, sulindac, meloxicam, chlorzoxazone, fenbufen, ibuprofen, diclofenac, indometacin, benorilate, nimesulide, aceclofenac, oxaprozin, nabumetone, mefenamic acid, ke-toprofen, celecoxib added in the blank ground samples were extracted with 80% methanol and were separated from a ACQUITY UPLC BEH C18 column within 12 min with a gradient of methanol - ammonium acetate,a tandem quadrupole mass

  20. Influencia de la formulación de la glutamina en sus efectos sobre los sistemas antioxidantes y de destoxificación hepática en la rata Effects of glutamine on antioxidants systems and hepatic detoxification in rats: influence of formulation

    Directory of Open Access Journals (Sweden)

    J. J. Ortiz de Urbina

    2004-03-01

    diets with L-glutamine or with L-alanyl-L-glutamine has on the balance of oxidants/antioxidants in the liver and on detoxification systems mediated by P-450 cytochrome in rats. Material and methods: Central catheters were inserted in the animals (n = 60 and they were randomly assigned to one of the following groups: a control group (C with oral feeding and I.V. infusion of saline solution, a total parenteral nutrition group without glutamine (TPN without GLN, a parenteral nutrition group with glutamine supplement (TPN GLN, and a total parenteral nutrition group with a supplement of alanine-gluta-mine dipeptide (20 g/L (TPN ALA-GLN. The parenteral nutrition provided was all isocaloric and isonitrogenated, and the infusions were administered at a speed of 2 ml/h over 5 days. Results: In the animals of the group without GLN, the liver concentration of glutathione was reduced while the levels of thiobarbituric acid reaction products (TBARS increased. Supplementing with either glutamine or ala-nine-glutamine normalized the levels of glutathione but the TBARS levels only fell in the group with the dipeptide. This effect was parallel to the partial recovery of the antioxidant enzyme activities analyzed. The liver concentrations of P-450 cytochrome, P-450 cytochrome dependent mono-oxygenases and the clearance of antipyrine were not modified by the supplements of glutamine or alanine-glutamine. Conclusions: Our data suggest a greater protection by alanine-glutamine supplements against the injury produced by free radicals during TPN and the absence of any effect with either glutamine or alanine-gluta-mine supplements on the oxidative metabolism of the liver.