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Sample records for antipyrine

  1. Antipyrine-Benzocaine Otic

    Science.gov (United States)

    ... benzocaine benzocaine and antipyrine benzocaine, antipyrine, and zinc acetate benzocaine, chloroxylenol, and hydrocortisone chloroxylenol and pramoxine chloroxylenol, pramoxine, and hydrocortisone BACKGROUND: ...

  2. Antipyrine clearance during experimental and occupational exposure to toluene

    DEFF Research Database (Denmark)

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

    1983-01-01

    Exposure to toluene vapour enhances hepatic microsomal enzyme function in animals as assessed by the metabolism of the test drug antipyrine. Thirty six printing trade workers with long term occupational exposure to a mixture of organic solvents and 39 matched controls were randomly allocated into...

  3. Spectrophotometric study of lanthanoid complexes with antipyrine and salicylic acid

    International Nuclear Information System (INIS)

    The extraction-spectrophotometric method has been used to study lanthanoid ion complexing (Pr, Nd, Ho and Er) with antipyrine (Ant) and salicylic acid (Sal). The component relationship in different-ligand compounds Ln:Aut:Sal=2:3:6 and solvate number equal to 5 are determined; molar extinction coefficients of binary and different-ligand compounds are calculated. Oscillator strengths of absorption bands corresponding to supersensitive transitions of neodymium, holmium, erbium and some most intensive praseodymium bands are calculated. The study of IR spectra of investigated compounds allows to conclude on formation of coordination bonds of the central atom with the antipyrine molecule through the oxygen of the carbonyl group as well as on carboxyl group hydrogen substitution for metal and formation of coordination bond with OH group in salicylic acid molecules

  4. Effect of antipyrine coadministration on the kinetics of acetaminophen and lidocaine.

    Science.gov (United States)

    Blyden, G T; Greenblatt, D J; LeDuc, B W; Scavone, J M

    1988-01-01

    Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received: 1, antipyrine 1.0 g intravenously (i.v.); 2, acetaminophen 650 mg i.v.; 3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml.min-1.kg-1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen VZ was reduced (1.14 vs 1.00 l.kg-1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml.min-1.kg-1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine VZ (2.6 vs 2.7 l.kg-1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml.min-1.kg-1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine. PMID:3197750

  5. 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.

  6. Differential effect of cigarette smoking on antipyrine oxidation versus acetaminophen conjugation.

    Science.gov (United States)

    Scavone, J M; Greenblatt, D J; LeDuc, B W; Blyden, G T; Luna, B G; Harmatz, J S

    1990-01-01

    The effect of cigarette smoking on drug oxidation and conjugation was studied using antipyrine and acetaminophen as marker compounds. For the antipyrine study, healthy cigarette smokers (n = 30) and nonsmoking controls (n = 53) received a single 1.0-gram intravenous dose of antipyrine. For the acetaminophen study, 14 smokers and 15 nonsmokers received a 650-mg intravenous dose of acetaminophen. The clearance of antipyrine was significantly increased (0.93 vs. 0.60 ml/min/kg, p less than 0.0001) and elimination half-life was correspondingly reduced (8.9 vs. 13.0 h, p less than 0.0001) in smokers compared to nonsmoking controls. Total recovery of antipyrine and metabolites excreted in urine did not differ between groups, but there was a significantly increased fractional clearance of antipyrine via formation of 4-hydroxyantipyrine and 3-hydroxymethyl metabolites in smokers. Fractional clearance via formation of norantipyrine did not differ significantly between groups. Comparison of acetaminophen kinetics between smokers and nonsmokers indicated no significant differences in elimination half-life, clearance or volume of distribution. Thus, cigarette smoking is more likely to induce drug oxidation rather than drug conjugation. However, not all oxidative pathways are equally influenced; induction effects of smoking are highly substrate selective and pathway specific. PMID:2345775

  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. Synthesis and Spectral Investigations of Some Platinum Metals Ions Coordination Compounds of 4[N-(Furan-2'-carboxalidene)Amino]Antipyrine Thiosemicarbazone and 4[N-(3',4',5'-Trimethoxybenzalidene)Amino]Antipyrine Thiosemicarbazone

    OpenAIRE

    Ram K. Agarwal; PRASAD, Surendra

    2005-01-01

    The present work describes the synthesis and spectral properties of some platinum metals chlorides coordination compounds of 4[N-(-(furan-2'-carboxalidene)amino]antipyrine thiosemicarbazone (FFAAPTS) and 4[N-(3',4',5'-trimethoxybenzalidene)amino]antipyrine thiosemicarbazone (TMBAAPTS). All the compounds have the general composition MCl2(L) (M = Pd2+ or Pt2+ ; L = FFAAPTS or TMBAAPTS) or MCl3(L) (M = Ru3+ , Rh3+ or Ir3+ ; L = FFAAPTS or TMBAAPTS). All the complexes...

  10. Synthesis and characterization of some oxocation(IV) coordination compounds of Schiff bases derived from 4-amino antipyrine

    International Nuclear Information System (INIS)

    The reaction of oxozirconium(IV) chloride with 4[N-2'-nitrobenzalidene) amino] antipyrine (2'-NO2BAAP), 4[N-(3'-nitrobenzalidene) amino] antipyrine (3'-NO2BAAP), 4[N-(benzalidene) amino] antipyrine thiosemicarbazone (BAAPT), 4[N-dimethyl aminobenzalidene) amino] antipyrine thiosemicarbazone (DABAAPT), 4[N-(4-methoxybenzalidene) amino] antipyrine thiosemicarbazone (MBAAPT) and 4[N-(4-hydroxy-3-methoxybenzalidene) amino] antipyrine thiosemicarbazone (HMBAAPT) and with oxovanadium(IV) salts with BAAPT and DABAAPT resulted in the formation of ZrOCl2.2L.H2O (L = 2'-NO2BAAP, 3'-NO2BAP, BAAPT, DABAAPT, MBAAPT or HMBAAPT and VOX2.L.nH2O (X = Cl,Br,I,NO3 or NCS, n=0, X=ClO4, n=1; L=BAAPT or DABAAPT) respectively. The structure of the complexes were assigned on the basis of elemental analyses, conductivity, molecular weight, magnetic moment, infrared and electronic spectral data. IR spectral data suggest the bidentate nature (N,O) of 2'-NO2BAAP and 3'-NO2BAAP, while the thiosemicarbazones behave as tridentate. (N,N,S) ligands. The probable coordination number of zirconium is either six eight and vanadium is five. Thermal properties of the compounds have been investigated through thermogravimetric analysis. (author). 43 refs, 6 tabs

  11. Synthesis and characterization of some oxocation(IV) coordination compounds of Schiff bases derived from 4-amino antipyrine

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, R.K.; Chakraborti, I. [Dept. of Chemistry, Lajpat Rai College, Sahibabad (India)

    1994-12-31

    The reaction of oxozirconium(IV) chloride with 4[N-2`-nitrobenzalidene) amino] antipyrine (2`-NO{sub 2}BAAP), 4[N-(3`-nitrobenzalidene) amino] antipyrine (3`-NO{sub 2}BAAP), 4[N-(benzalidene) amino] antipyrine thiosemicarbazone (BAAPT), 4[N-dimethyl aminobenzalidene) amino] antipyrine thiosemicarbazone (DABAAPT), 4[N-(4-methoxybenzalidene) amino] antipyrine thiosemicarbazone (MBAAPT) and 4[N-(4-hydroxy-3-methoxybenzalidene) amino] antipyrine thiosemicarbazone (HMBAAPT) and with oxovanadium(IV) salts with BAAPT and DABAAPT resulted in the formation of ZrOCl{sub 2}.2L.H{sub 2}O (L = 2`-NO{sub 2}BAAP, 3`-NO{sub 2}BAP, BAAPT, DABAAPT, MBAAPT or HMBAAPT and VOX{sub 2}.L.nH{sub 2}O (X = Cl,Br,I,NO{sub 3} or NCS, n=0, X=ClO{sub 4}, n=1; L=BAAPT or DABAAPT) respectively. The structure of the complexes were assigned on the basis of elemental analyses, conductivity, molecular weight, magnetic moment, infrared and electronic spectral data. IR spectral data suggest the bidentate nature (N,O) of 2`-NO{sub 2}BAAP and 3`-NO{sub 2}BAAP, while the thiosemicarbazones behave as tridentate. (N,N,S) ligands. The probable coordination number of zirconium is either six eight and vanadium is five. Thermal properties of the compounds have been investigated through thermogravimetric analysis. (author). 43 refs, 6 tabs.

  12. 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.

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

    International Nuclear Information System (INIS)

    Highlights: • The antipyrine decomposition exhibited a pseudo-first-order kinetics pattern well. • The kobs with irradiance or oxidant dosage presented a linear relationship well. • The kobs exhibit an exponential trend as a function of [AP]0 for three systems. • UV/H2O2 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/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

  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. 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.

  16. Organic-solvent-free extraction systems with phase separation based on antipyrine, sulfo salicylic acid, sodium sulphate and water for extraction of metal ions macro amounts

    International Nuclear Information System (INIS)

    It is determined that the aqueous system delamination occurred in the case of pouring of 2 mol/l solutions of antipyrin and sulfo salicylic acid in the molar ratio of 2 : 1. Volume of lower organic phase equal to 3.25 ml depends on the concentration of original components, appending salting-out agent and the medium acidity. The ratio of components antipyrin : sulfo salicylic acid : H2O into organic phase was determined. The optimal conditions for the macro amounts extraction of Fe (III), Ga (III), In (III), and Tl (III) were established. The extraction mechanism and the composition of extracted complexes were suggested. (author)

  17. Synthesis, spectral and thermal studies of some lanthanide(III) complexes of 4-[N-(benzalidene) amino] antipyrine thiosemicarbazone

    International Nuclear Information System (INIS)

    A new series of sixteen lanthanide(III) complexes of 4[N-(benzalidene) amino] antipyrine thiosemicarbazone (BAAPTS) with the general composition LnX3.n(BAAPTS) (X =Cl-, n = 2; X = NO-3, n = 1; Ln = La, Pr, Nd, Sm, Gd, Tb, Dy and Ho) have been synthesized and characterized by chemical analysis, conductance, molar weight, magnetic moments measurements, infrared and electronic spectra. The ligand BAAPTS behaves as neutral tridentate (N, N, S) ligand. The probable coordination number is nine in these complexes. (author)

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs.

    Science.gov (United States)

    Koyanagi, Takashi; Yamaura, Yoshiyuki; Yano, Koji; Kim, Soonih; Yamazaki, Hiroshi

    2014-10-01

    1. The pharmacokinetics of acetaminophen (marker of gastric emptying), antipyrine (marker of hepatic metabolic activity and total body water), diazepam (lipophilic and highly distributed), diphenhydramine (hepatic blood flow-limited and alpha-1 acid glycoprotein bound) and ofloxacin (renally eliminated) were evaluated in cynomolgus monkeys (3-18 years old) and beagle dogs (2-11 years old) as models in elderly persons. 2. Gastric pH fluctuated with aging in monkeys and dogs. The concentration of alpha-1 acid glycoprotein appeared to be increased by aging. There were no age-related differences in the absorption rates of the drugs under the conditions used in the study. Total body fat increased and water decreased in monkeys, but these parameters did not change in dogs. 3. Hepatic blood flow decreased in both species, but a significant decrease of hepatic clearance was only seen in monkeys. Renal clearance decreased significantly with age in monkeys and showed a tendency to decrease in dogs. 4. Age-related alterations of physiological parameters in monkeys are in agreement with clinical observations in humans, except for the lack of a change in the plasma albumin concentration. Therefore, this study suggests that monkey might be a suitable animal model for prediction of age-related changes in pharmacokinetics in humans. PMID:24650193

  3. Synthesis and structural investigations of some five-coordinated oxovanadium(IV) complexes of 4[N-(benzylidene)amino] antipyrine semicarbazone

    International Nuclear Information System (INIS)

    The synthesis and spectral characteristics of a new series of five coordinated oxovanadium(IV) complexes of 4[N-(benzylidene) antipyrine semicarbazone (BAAPS) with general composition VOX2.BAAPS (X=Cl, Br, I, No3 or NCS) and VO(ClO4)2. BAAPS.H2O are reported together with molecular conductivity, molecular weights, magnetic susceptibility, infrared and electronic spectra. In all the complexes, the BAAPS behaves as neutral tridentate (N,N,O) ligand. (author). 12 refs., 3 tabs

  4. A new recycling technique for human placental cotyledon perfusion: application to studies of the fetomaternal transfer of glucose, inulin, and antipyrine

    International Nuclear Information System (INIS)

    A previously described technique has been modified to permit the continuously recirculating perfusion of the separate maternal and fetal circulations of an isolated cotyledon of human placenta. Viability of the perfused cotyledons was established by measurements of oxygen consumption (average, 0.18 ml/gm/hr), glucose utilization (average, 1.0 mg/gm/hr), and lactate production (less than 0.01 mumol/gm/hr), and integrity of the placental barrier by the failure of India ink, 125I-albumin, or 35S-sulfobromophthalein to cross from fetal to maternal circulation. Clearance of 3H-inulin from the fetal circuit, 0.0059 +/- 0.0005 (SE) ml/min/gm, corresponded to 2.5% of its clearance by the adult human kidney. Clearance of 14C-antipyrine was 0.013 +/- 0.003 ml/min/gm. After introduction into the fetal circuit, the observed appearance of both inulin and antipyrine in the maternal circuit closely paralleled curves predicted by a simple mathematical model. The use of a continuously recirculating perfusion system is technically feasible, and has advantages over the single-pass technique for studying transplacental transfer of metabolites with a low efficiency of extraction

  5. 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

  6. The 14C-monomethylamino-antipyrine breath test as in vivo parameter for characterizing the induction of the drug catabolizing enzyme system in the guinea pig

    International Nuclear Information System (INIS)

    The aim of these investigations was to help clarify the following questions: 1) Does MAAP, following 14C labelling of the exocyclic aminomethyl group, offer a suitable substrate for a breath test in guinea pigs. 2) Which procedures for evaluating the 14C exhalation curves of the breath test are especially valid. 3) Can an induction of the drug catabolizing enzyme system following pre-treatment with various inducing substances be detected by the 14C-MAAP breath test. 4) Do inducer-specific differences arise in response to the 14C-MAAP breath test by which the inducers can be characterized. 5) Is monomethylamino-antipyrine similar to amidopyrine in that it is a suitable independent in vivo parameter for the drug metasbolizing enzyme system in the liver of guinea pigs. (orig./MG)

  7. Enhancement effect of p-menthane-3,8-diol on in vitro permeation of antipyrine and indomethacin through Yucatan micropig skin.

    Science.gov (United States)

    Fujii, Makiko; Takeda, Yasuhiro; Yoshida, Minako; Matsumoto, Mitsuo; Watanabe, Yoshiteru

    2004-07-01

    The enhancing effect of p-Menthane-3,8-diol (MDO) on skin permeation of antipyrine (ANP) and indomethacin (IM) through Yucatan micropig skin in vitro was compared with 1-menthol. p-Menthane-3,8-diol is a metabolite of 1-menthol and has little odor. It is easy to combine the vehicle because of lower lipophilicity than 1-menthol. All formulations contained 40% (v/v) ethanol. The permeation of ANP increased with MDO about three times that without enhancer by increasing ANP concentration in the skin. However, the MDO effect was about a quarter that of 1-menthol. The permeation of IM with MDO was about 15 times that with no enhancer and it was almost the same as that with 1-menthol. The lag time of permeation was not significantly changed by MDO, which was not so in the case of 1-menthol. Skin concentration of IM increased about 11 times and six times with MDO and 1-menthol, respectively. MDO and 1-menthol partitioned to the skin relatively high concentrations, 5.9 and 2.5 mg/ cm3, respectively. The solubility of IM in the skin was improved by MDO, and consequently, the permeation of IM was enhanced. PMID:15285341

  8. Optical properties and device characteristics of 2-(antipyrin-4-ylhydrazono)-2-(4-nitrophenyl)acetonitrile thin films for photodiode applications

    Science.gov (United States)

    El-Menyawy, E. M.; Zedan, I. T.

    2015-02-01

    2-(Antipyrin-4-ylhydrazono)-2-(4-nitrophenyl)acetonitrile (AHNA) films were deposited via thermal evaporation technique. The optical properties of AHNA films and electrical characteristics of Au/AHNA/n-Si/Au heterojunction diode have been reported. The optical properties of AHNA films were investigated using the spectrophotometric measurements of optical transmittance and reflectance over spectral range 190-2500 nm. The films have indirect allowed optical band gap of 3.6 eV. The refractive index of the films was calculated and the dispersion parameters of the films were determined on the light of the single oscillator model. The electrical properties of Au/AHNA/n-Si/Au heterojunction diode were studied in terms of current-voltage characteristics. The device showed rectification behaviour with a rectification ratio of 100 at ±1 V. The conduction mechanisms and diode parameters such as ideality factor, barrier height and series resistance of the device were determined. The device under illumination showed photovoltaic properties. The short circuit current and open circuit voltage were found to be function of illumination intensity. The device satisfies the conditions to be used as photodiode.

  9. 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. PMID:24068187

  10. 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.

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

    International Nuclear Information System (INIS)

    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

  12. 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.

  13. 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. PMID:26840714

  14. Synthesis and characterization of some metal complexes derived from azo compound of 4,4‧-methylenedianiline and antipyrine: Evaluation of their biological activity on some land snail species

    Science.gov (United States)

    AbouEl-Enein, Saeyda A.; Emam, Sanaa M.; Polis, Magdy W.; Emara, Esam M.

    2015-11-01

    A novel series of metal complexes of the azo dye; bis-(1,5-dimethyl-4-[(E)-(3-methylphenyl)diazenyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one) derived from 4,4‧-methylenedianiline and antipyrine was synthesized and characterized by different spectral, thermal and analytical methods. The tetradentate ligand reacts with the metal ions as a half unit. All complexes display an octahedral geometry, except Pd(II) complex (7) which has a square planar one. The thermal studies reveal that the complexes have higher thermal stability comparable with that of the free ligand. The activation thermodynamic parameters, such as activation energy (E*), enthalpy of activation (ΔH*), entropy of activation (ΔS*) and Gibbs free energy (ΔG*) have been calculated using DTG curves. The ESR spectra of the solid Cu(II) complexes showed an axial symmetry with 2B1g as a ground state and hyperfine structure. The biological activities of the ligand, as well as its metal complexes have been tested in vitro against two land snail species; Eobania vermiculata and Monacha obstructa. The results show that all the tested compounds have significant biological activities against the two tested land snail species with different sensitivity levels.

  15. 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%.

  16. Structure and bonding of some newly synthesized complexes of lanthanide(III) complexes of 4[N-(p-dimetaylaminobenzalidene) amino] antipyrine thiosemicarbazone

    International Nuclear Information System (INIS)

    A series of complexes of the type LnX3.2(DABAAPTS), where Ln = La, Pr, Nd, Sm, Gd, Tb, Dy and Ho, X = ClO4-, or NCS-, DABAAPTS=4[N- (p-dimethylaminobenzalidene) amino] anti pyrine thiosemicarbazone have been synthesized and characterized on the basis of elemental analysis, molecular weight measurements, molar conductance, room temperature magnetic moment, infrared and electronic spectral data. The ligand DABAAPTS behaves as neutral tridentate (N2S) ligand. (author)

  17. 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%.

  18. 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.

  19. 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.

  20. Synthesis, Spectroscopic and Physicochemical Characterization and Biological Activity of Co(II) and Ni(II) Coordination Compounds with 4-Aminoantipyrine Thiosemicarbazone

    OpenAIRE

    Ram K. Agarwal; Surendra Prasad

    2004-01-01

    We describe the synthesis and characterization of cobalt(II) and nickel(II) coordination compounds of 4[N-(furan-2’-aldimine)amino]antipyrine thiosemicarbazone (FFAAPTS) and 4[N-(4'-nitrobenzalidene) amino]antipyrine thiosemicarbazone (4'-NO2BAAPTS). All the isolated compounds have the general composition MX2(L)(H2O) (M = Co2+ or Ni2+; X = Cl, Br, NO3, NCS or CH3COO; L = FFAAPTS or 4'-NO2BAAPTS) and M(ClO4)2(L)2 (M = Co2+ or Ni2+; L = FFAAPTS or 4'-NO2BAAPTS). Infrared spectral studies i...

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

    OpenAIRE

    Ram K. Agarwal; 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...

  2. 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...

  3. Rate-controlled rectal drug delivery in man with a hydrogel preparation

    NARCIS (Netherlands)

    Leede, de L.G.J.; Boer, de A.G.; Pörtzgen, E.; Feijen, J.; Breimer, D.D.

    1986-01-01

    Cylindrical hydrogels of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent were prepared by radical polymerization at 70°C. After washing they were soaked in an aqueous drug solution of antipyrine or theophylline. The in vitro drug release experiments

  4. 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)pyridi......(a)pyrene the curve fitting failed. These prevalidation results give confidence for harmonization of the placental perfusion system to be used as one of the test methods in a panel for reproductive toxicology to model placental transfer in humans.......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...

  5. 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.

  6. 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.

  7. 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

    highly ranked no matter which parameter was used. Antipyrine normalization resulted in the following ranking order of compounds according to AUC(120NORM) values: NDMA = EtOH = BPA = IQ =AA = GA = PCB180 = PhIP = AFB1 > DON = BP = PCB52 = TCDD. As the variance in all parameters within a study decreased...

  8. Skin Disposition of Drugs after Topical Application in Hairless Rats

    OpenAIRE

    柳本, 剛; 林, 輝朗; 長谷川, 哲也; 関, 俊暢; 從二, 和彦; 杉林, 堅次; 森本, 雍憲

    1999-01-01

    Drug fraction transported from a topical formulation on skin to subsutaneous tissues or muscles is dependent on the physicochemical properties of the entrapped drug. Cutaneous disposition of model drugs, antipyrine(ANP), lidocaine (LC) and piroxicam (PXC) as well as flurbiprofen (FP) was thus evaluated in hairless rats in which an agar gel disc was subcutaneously inserted into abdominal region as a drug receptor and a drug donor cell was placed above it. Time courses of plasma level and agar ...

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

    OpenAIRE

    Espejo, Azahara; Aguinaco, Almudena; Amat Payá, Ana María; Fernando J. Beltrán

    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 ...

  10. The Ex Vivo Human Placental Transfer of the Anti-HIV Nucleoside Inhibitor Abacavir and the Protease Inhibitor Amprenavir

    OpenAIRE

    Bawdon, R E

    1998-01-01

    Objective: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model.Methods: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by ...

  11. The ex vivo human placental transfer of the anti-HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir.

    OpenAIRE

    Bawdon, R E

    1998-01-01

    OBJECTIVE: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model. METHODS: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by...

  12. 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.

  13. Application of Osmotic Pumps for Sustained Release of 1-Aminobenzotriazole and Inhibition of Cytochrome P450 Enzymes in Mice: Model Comparison with the Hepatic P450 Reductase Null Mouse.

    Science.gov (United States)

    Stringer, Rowan A; Ferreira, Suzie; Rose, Jonathan; Ronseaux, Sebastien

    2016-08-01

    The effectiveness of controlled release 1-aminobenzotriazole (ABT) administration to inhibit cytochrome P450 (P450) enzymes has been evaluated in mice. To maximize the duration of P450 inhibition in vivo, ABT was administered via an osmotic pump. The degree of P450 inhibition was compared with that achieved with a single bolus dose of ABT. Two-hour prior subcutaneous treatment of mice with ABT (50 mg/kg) inhibited antipyrine clearance by 88%. A less pronounced inhibitory effect (29% reduction in clearance) was observed when ABT was administered 24-hours before antipyrine administration, indicating partial restoration of P450 activity during this longer pretreatment time. The duration of ABT in mice was very short (mean residence time = 1.7 hours) after subcutaneous bolus administration. When the inhibitor was delivered by an osmotic pump, maximum blood concentrations of the inhibitor were observed 24 hours after device implantation and were maintained at steady state for 6 days. Inhibition of P450 activity, as measured by antipyrine clearance, was confirmed at 24 hours and 120 hours after pump implantation, highlighting the utility of this method as a longer-term model for P450 inhibition in mice. The magnitude of P450 inhibition in ABT-treated mice was compared with that in hepatic P450 reductase null mice and both models were comparable. In vivo ABT administration by an osmotic pump offers an effective approach for longer-term P450 inhibition in mice and avoids the necessity for multiple dosing of the inhibitor. PMID:27271368

  14. 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 placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008....... 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...

  15. 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.

  16. CriticalSorb promotes permeation of flux markers across isolated rat intestinal mucosae and Caco-2 monolayers

    OpenAIRE

    Brayden, David James; Bzik, V. A.; Lewis, A L; Illum, L.

    2012-01-01

    Purpose CriticalSorb™ is a novel absorption enhancer based on Solutol® HS15, one that has been found to enhance the nasal transport. It is in clinical trials for nasal delivery of human growth hormone. The hypothesis was that permeating enhancement effects of the Solutol®HS15 component would translate to the intestine. Methods Rat colonic mucosae were mounted in Ussing chambers and Papp values of [14C]-mannitol, [14C]-antipyrine, FITC-dextran 4000 (FD-4), and TEER values were calcul...

  17. Synthesis, Spectroscopic and Physicochemical Characterization and Biological Activity of Co(II and Ni(II Coordination Compounds with 4-Aminoantipyrine Thiosemicarbazone

    Directory of Open Access Journals (Sweden)

    Ram K. Agarwal

    2004-01-01

    Full Text Available We describe the synthesis and characterization of cobalt(II and nickel(II coordination compounds of 4[N-(furan-2’-aldimineamino]antipyrine thiosemicarbazone (FFAAPTS and 4[N-(4'-nitrobenzalidene amino]antipyrine thiosemicarbazone (4'-NO2BAAPTS. All the isolated compounds have the general composition MX2(L(H2O (M = Co2+ or Ni2+; X = Cl, Br, NO3, NCS or CH3COO; L = FFAAPTS or 4'-NO2BAAPTS and M(ClO42(L2 (M = Co2+ or Ni2+; L = FFAAPTS or 4'-NO2BAAPTS. Infrared spectral studies indicate that both the thiosemicarbazones coordinate in their neutral form and they act as {N,N,S} tridentate chelating ligands. Room temperature magnetic measurements and electronic spectral studies suggest the distorted octahedral geometries of the prepared complexes. Thermogravimetric studies are also reported and the possible structures of the complexes are proposed. Antibacterial and antifungal properties of these metal-coordination compounds have also been studied.

  18. 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.

  19. 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.

  20. 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.

  1. Maternal-fetal transfer of indocyanine green across the perfused human placenta.

    Science.gov (United States)

    Rubinchik-Stern, Miriam; Shmuel, Miriam; Bar, Jacob; Eyal, Sara; Kovo, Michal

    2016-07-01

    Indocyanine green (ICG) is an FDA-approved near-infrared imaging probe, given also to pregnant women. We aimed to characterize ICG's transplacental transfer using the ex-vivo perfusion model. Placentas were obtained from caesarean deliveries. Cotyledons were cannulated and dually perfused. ICG, 9.6μg/mL and antipyrine (50μg/mL) were added to the maternal circulation in the absence (n=4) or the presence of the organic anion transporting polypeptide (OATPs) inhibitor rifampin (10μg/mL; n=5) or the P-glycoprotein inhibitor valspodar (2μg/mL; n=3). ICG's maternal-to-fetal transfer was evaluated over 180min. The cumulative percent of ICG in the fetal reservoir was minor. When ICG transfer was normalized to that of antipyrine, it was lower in the presence of rifampin (a 41% decrease; p<0.05). Valspodar did not appear to modify the kinetics of ICG. ICG's transplacental transfer is minimal and is probably OATP-mediated. The placenta is an effective protective barrier to ICG's distribution into the fetus. PMID:27132189

  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. Skin perfusion pressure on the legs measured as the external pressure required for skin reddening after blanching

    DEFF Research Database (Denmark)

    Holstein, P; Nielsen, P.E.; Lund, P;

    1980-01-01

    The skin perfusion on the calf was measured photo-electrically and by isotope washout technique using external counter pressure by a blood pressure cuff. By the photocell the skin blanching threshold external pressure (BTEP) was recorded on histamine flared red skin. By isotope washout technique...... the skin blood flow cessation external pressure (FCEP) was recorded using intra-dermal [131I-]-antipyrine mixed with histamine in estimating the skin blood flow. The external pressure was measured with an airfilled plastic cushion connected to a mercury manometer. Over a wide range of pressures as obtained......Hg (SD 8.7). As compared to the intra-arterial blood pressure the BTEP was found to lie close to the mean blood pressure in normal subjects as well as in hypertensive subjects. The present data indicate that the skin perfusion pressure on the legs can be measured by the rapid photo-electric technique...

  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. 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.

  7. 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....

  8. 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...

  9. Determination of phenol in locally grown fruits and vegetable by spectrophotometric method

    International Nuclear Information System (INIS)

    Spectrophotometric method for the determination of phenol in the sample of locally grown fruits apple, pear, sweet orange and vegetable radish of Quetta, Hyderabad and Nawabshah are described juices from these fruits and vegetable were squeezed, filtered and decolorized with charcoal. The antipyrine dye formed by reaction between phenol and 4-aminoantipyrine was analyzed. The calibration graphs were prepared in the range of 0.5 to 4 ppm of phenol. Phenol in apple, pear and sweet orange was found to be in the range of 1-1.2 ppm and in radish was found to be 0.5 ppm. Possible source of organic pollutant were pointed out and were discussed. Limits of detection of the method was investigated and was found to be 0.2 mu g/ml

  10. 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.

  11. 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.

  12. Design and evaluation of radiotracers for determination of regional cerebral blood flow with PET

    International Nuclear Information System (INIS)

    The tracer kinetics of 4-Fluoro(18F)-, 4-Bromo(82Br)- and 4-Iodo(125I)-antipyrine and 15O-water were compared in a cat or baboon animal model. First-pass cerebral extraction and clearance with alterations in PaCO2 were measured for whole brain. The Renkin/Crone model was used to evaluate brain capillary permeability-surface area product for 4-18FAP in cats. Positron-emission-tomographic measurements required development of an instrument and technique for control of the arterial concentration of the radiotracer as a ramp function, so that tracer concentration changes due to radioactive decay or altered physiological processes could be accurately described with PET. Pharmacokinetic and tissue-distribution studies in cats were used to determine dosimetry for 4-18FAP. 4-Bromoantipyrine labeled with 78Br (t = 6.5 m) is suggested as a tracer for determination of rCBF with PET

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. LC-QTOF MS screening of more than 1,000 licit and illicit drugs and their metabolites in wastewater and surface waters from the area of Bogotá, Colombia.

    Science.gov (United States)

    Hernández, Félix; Ibáñez, María; Botero-Coy, Ana-María; Bade, Richard; Bustos-López, Martha Cristina; Rincón, Javier; Moncayo, Alejandro; Bijlsma, Lubertus

    2015-08-01

    A large screening of around 1,000 emerging contaminants, focused on licit and illicit drugs and their metabolites, has been made in urban wastewaters (both influent and effluent) and surface waters from the area of Bogotá, Colombia. After a simple generic solid-phase extraction (SPE) step with Oasis hydrophilic-lipophilic balanced (HLB) cartridges, analyses were made by ultra high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) under MS(E) mode (sequential acquisition of mass spectra at low energy (LE) and high collision energy (HE)). Accurate mass measurements and the information provided by MS(E) on the presence of the (de)protonated molecule and fragment ions allowed the reliable identification of the compounds detected, even without reference standards being available in some cases (tentative identification). The compounds most frequently found were acetaminophen/paracetamol, carbamazepine and its dihydro-dihydroxylated metabolite, clarithromycin, diclofenac, ibuprofen, gemfibrozil, lincomycin, losartan, valsartan, the two metabolites of metamizole (4-acetamido-antipyrine and 4-formylamino-antipyrine), sucralose, and cocaine and its main metabolite benzoylecgonine. Caffeine, the sweetener saccharin, and two hydroxylated metabolites of losartan were tentatively identified in almost all samples analyzed. Pharmaceutical lidocaine was tentatively identified and subsequently confirmed with reference standard. For the first time, a general overview of the occurrence of drugs and their metabolites in the aquatic environment of Colombia has been reported. In the near future, target methodologies, typically based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), will need to be set up for accurate and sensitive quantification of the contaminants selected on the basis on the information provided in the present paper. PMID:26084545

  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. Fetoplacental deamination and decarboxylation of leucine

    International Nuclear Information System (INIS)

    Fetal and placental metabolism of leucine (Leu) and ketoisocaproic acid (KIC) were studied in seven fetal lambs at 132 +/- 1.3-days gestation. Fetal infusions of [1-13C]Leu, [1-14C]Leu, and antipyrine were carried out for 4 h. Uterine and umbilical blood flows were measured using the antipyrine steady-state diffusion technique. Leu and KIC concentrations, [14C]Leu-specific activities, 14CO2, [13C]Leu, and [13C]KIC enrichment (mole percent enrichment) were measured in the maternal artery, uterine vein, and umbilical artery and vein to calculate net fluxes of tracee and tracer molecules between fetus and placenta and between the uteroplacenta and the maternal circulation. There were net Leu and KIC fluxes into the fetus from the placenta with the KIC flux equal to approximately 19% of the combined Leu plus KIC flux. In addition, there was a net KIC flux into the uterine circulation. The fraction of infused tracer Leu escaping the placenta into the mother was small (approximately 6%). By contrast, there was a rapid exchange of tracer Leu carbon between placenta and fetus resulting in a significant flux of labeled KIC from placenta to fetus. Approximately 20% of the infused tracer carbon was converted to CO2 within the fetus. This rate of conversion was greater than 80% of the total fetoplacental conversion rate and significantly higher than the flux of KIC tracer carbon from placenta to fetus. Fetal KIC decarboxylation rate, calculated from the fetal KIC enrichment data, was 2.83 +/- 0.40 mumol.min-1.kg fetus-1 and approximately 60% of the combined net Leu and KIC flux into the fetus from the placenta

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

    International Nuclear Information System (INIS)

    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 [14C]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 [14C]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

  1. Synthesis and Spectroscopic Property of Acridinium-9-sulfonamides%新型吖啶-9-磺酰胺衍生物的合成及光谱学性质

    Institute of Scientific and Technical Information of China (English)

    穆小静; 肖尚友; 王建超; 吴彦蕾; 夏之宁

    2009-01-01

    By introducing an electro-withdrawing antipyrine group, N-(p-toluenesulfonyl)-N-(4-antipyrine)-10-methylacridinium-9-carboxamide triflate was prepared. The UV, FL and CL properties of the target compound and of its precursor were investigated by comparing with those of the model compound N-(p-toluenesulfonyl)-N-phenyl-10-methylacridinium-9-carboxamide triflate and the corresponding precursor respectively. The results show that acridine sulfonamide with a heterocyclic antipyrine group exhibits blue shift of both UV absorption and of maximum excitation wavelength(λex) and emission wavelength(λem) in FL spectra, comparing with the corresponding model compound. The λex of the final target and its precursor are 268 and 274 nm, respectively; and the λem are 321 and 327 nm, respectively, while λex of the model compound and its unmethylated precursor are 365 and 359 nm, respectively; and the λem are 504 and 440 nm, respectively. Moreover, the chemiluminescence of the final target compound triggered by H2O2 could finish within 1.1 s; and the quantum yield is similar to that of the model compound, being 5.6 times high as that of luminol.%在吖啶磺酰胺分子中引入杂环安替比林吸电性基团,合成了N-对甲基苯磺酰基-N-(4-安替比林)-10-甲基吖啶-9-磺酰胺三氟甲基磺酸鎓盐.最终产物与未甲基化的前体分别与模型化合物N-对甲基苯磺酰基-N-苯基-10-甲基吖啶-9-酰胺三氟甲基磺酸鎓盐及其前体的紫外-可见吸收光谱(UV)、荧光光谱(FL)进行比较.结果表明,引入杂环安替比林使吖啶磺酰胺的UV和FL谱发生了变化,尤其是FL谱的最大激发与发射峰的位置比相应的模型化合物大幅蓝移.最终产物及其前体的最大λex分别为268和274 nm; λem分别为321和327 nm.而模型化合物及前体最大λex分别为365和359 nm; λem分别为504和440 nm.H2O2引发的目标产物的化学发光(CL)在1.1 s完成;化学发光量子产率与模型化合物相

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

    International Nuclear Information System (INIS)

    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 132I--or 125I--antipyrine mixed with histamine. Out of the 11 cases with an SPP below 30 mmHg 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<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 previously been shown to be the case in below-knee amputations. (author)

  3. A modified scintigrafic technique for amputation level selection in diabetics

    International Nuclear Information System (INIS)

    A modified 123I-antipyrine cutaneous washout technique for the selection of amputation levels is described. The modifications imply a reduction of time needed for the examination by simultaneous recordings on different levels, and a better patient acceptance by reducing inconvenience. Furthermore, both skin perfusion pressure (SPP) and skin blood flow (SBF) are determined from each clearance curve. In a prospective study among 26 diabetic patients presenting with ulcers or gangrene of the foot, both SPP and SBF were determined preoperatively on the selected level of surgery and on adjacent amputation sites. These 26 patients underwent 12 minor foot amputations and 17 major lower limb amputations. Two of these amputations failed to heal. SBF values appeared indicative for the degree of peripheral vascular disease, as low SBF values were found with low SPP values. SPP determinations revealed good predictive values: All surgical procedures healed when SPP>20 mmHg, but 2 out of 3 failed when SPP<2 mmHg. If SPP values would have been decisive, the amputation would have been converted to a lower level in 6 out of 17 cases. This modified scintigrafic technique provides accurate objective information for amputation level selection. (orig.)

  4. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

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

    2010-01-01

    Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting the plac......Validation of in vitro test systems using the modular approach with steps addressing reliability and relevance is an important aim when developing in vitro tests in e.g. reproductive toxicology. The ex vivo human placental perfusion system may be used for such validation, here presenting...... 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, p... ml h(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100 ml 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...

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

    Science.gov (United States)

    He, Kai; 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 7days under saturated condition removed most PPCPs. PMID:27213846

  6. Macrolide antibacterials. Drug interactions of clinical significance.

    Science.gov (United States)

    von Rosensteil, N A; Adam, D

    1995-08-01

    Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine. PMID:7576262

  7. Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model

    Directory of Open Access Journals (Sweden)

    Pierre-Francois Ceccaldi

    2009-01-01

    Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L. After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes. Fetal Transfer Rate (FTR and Clearance Index (CLI were compared between the 2 phases. Results. In the control phase, the clearance index of lopinavir decreased from 0.401 ± 0.058 to 0.007 ± 0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L. When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [−0.156, −0.002], P=.046 and became positive for ritonavir. Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy.

  8. Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism

    DEFF Research Database (Denmark)

    Immonen, E; Kummu, M; Petsalo, A;

    2010-01-01

    M, n = 6) or Ko143 (specific inhibitor of ABCG2, 2 muM, n = 4) to study the role of ABCG2 inhibition in transfer while in Denmark perfusions were performed with (14)C-IQ alone. Critical parameters (leak from fetal to maternal circulation, pH values, blood gases, glucose consumption, the production of h......CG hormone and transport of antipyrine) were analyzed during the perfusions. (14)C-IQ on maternal and fetal sides was determined by liquid scintillation counting. In Finland IQ and its metabolites in final perfusates were determined also by LC/TOF-MS. ABCG2 expression and EROD activity (CYP1A1/2) were...... analyzed from perfused tissues. (14)C-IQ was easily transferred through the placenta from maternal to fetal side in both laboratories. Neither significant EROD activity nor IQ metabolites were found in placentas from non-smoking mothers. Inhibition of ABCG2 by GF120918 (FM-ratio of IQ 0.95) or Ko143 (FM...

  9. 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.

  10. Influence of type of ration on the growth rate and carcass quality of young goat

    International Nuclear Information System (INIS)

    Twelve young goats (six males and six females) weighing about 10 kg in body weight were divided into two groups and were offered the following rations: (A) all forage diet ad lib consisting of berseem hay and mineral supplements and (B) diet A + 250 gm concentrate mixture (per animal) consisting of 3 parts of maize and one part of wheat bran and mineral supplements. After a preliminary feeding period of 60 days a metabolism trial was conducted to determine nutrient utilization. The animals were continued further on the same ration for another 120 days; a feeding trial was conducted and the body composition was studied in six animals by injecting 5 ml of 10% antipyrine solution and the animals were sacrificed to study carcass characteristics. 50 μci of 14C tyrosine was injected 24 hours before slaughter and its incorporation into muscle proteins was determined. It has been observed that supplementation of the concentrate to the ration improved the performance of animals. The supplementation has improved growth rate to 38.5 g/day from 13 g/day of the forage fed group of animals. The results of the study are discussed. (author)

  11. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Energy Technology Data Exchange (ETDEWEB)

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

  12. 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.

  13. [Oral exposure testing in non-aspirin-induced analgesic intolerance].

    Science.gov (United States)

    Wiedow, O; Brasch, J; Christophers, E

    1996-12-01

    Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects. PMID:9081936

  14. Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids.

    Science.gov (United States)

    Yi, Qi-Feng; Yan, Jin; Tang, Si-Yuan; Huang, Hui; Kang, Li-Yang

    2016-07-01

    The aim of the present paper was to investigate the promoting activity of borneol on the transdermal permeation of drugs with differing lipophilicity, and probe its alterations in molecular organization of stratum corneum (SC) lipids. The toxicity of borneol was evaluated in epidermal keratinocyte HaCaT and dermal fibroblast CCC-HSF-1 cell cultures and compared to known enhancers, and its irritant profile was also assessed by transepidermal water loss (TEWL) evaluation. The promoting effect of borneol on the transdermal permeation of five model drugs, namely 5-fluorouracil, antipyrine, aspirin, salicylic acid and ibuprofen, which were selected based on their lipophilicity denoted by logp value, were performed using in vitro skin permeation studies. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to monitor the borneol-induced alteration in molecular organization of SC lipids. The enhancer borneol displayed lower cytotoxicity or irritation in comparison to the well-established and standard enhancer Azone. Borneol could effectively promote the transdermal permeation of five model drugs, and its enhancement ratios were found to be parabolic curve with the logp values of drugs, which exhibited the optimum permeation activity for relatively hydrophilic drugs (an estimated logp value of -0.5 ∼0.5). The molecular mechanism studies suggested that borneol could perturb the structure of SC lipid alkyl chains, and extract part of SC lipids, resulting in the alteration in the skin permeability barrier. PMID:26635061

  15. 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.

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

    International Nuclear Information System (INIS)

    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 mmHg, 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. The difference in failure rate is highly significant (P<0.01). Four out of 30 diabetic patients required reamputation as against 10 out of 30 non-diabetics (0.05< P<0.10) The average SPP was higher in the diabetic group: 57 mmHg (range 18-93 mmHg) compared with 34 mmHg (range 8-68 mmHg) in the non-diabetic group (P<0.001). The postoperative SPP measured on the stumps was on average 8 mmHg higher than the preoperative SPP (P<0.001). The increase took place mainly in stumps with an SPP above 20 mmHg explaining why the preoperative SPP values related so 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. (author)

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

    Science.gov (United States)

    Petersen, Brenden K; Ropella, Glen E P; Hunt, C Anthony

    2016-01-01

    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 validation, we will generate

  18. Transformation of phenazone-type drugs during chlorination.

    Science.gov (United States)

    Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2012-05-01

    Chlorination is one of the most popular disinfection steps for water treatment in Europe. However, chlorine can react with pharmaceuticals and other micropollutants leading to either their elimination or by-products being formed. These by-products are frequently not identified and therefore the consequences of chlorination can be underestimated. In this work, the degradation of two analgesics and antipyretics, phenazone (antipyrine) and propyphenazone, during chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). A quadrupole-time-of-flight (Q-TOF) system was used to follow the time course of the pharmaceuticals, and also used in the identification of the by-products. The degradation kinetics was investigated at different concentrations of chlorine (1-10 mg/L), bromide (0-100 μg/L) and sample pH (5.7-8.3) by means of a Box-Behnken experimental design. Depending on these factors, half-lives were in the ranges: 0.9-295 s for phenazone and 0.4-173 s for propyphenazone. Also, it was observed that chlorine concentration was a significant factor for propyphenazone, resulting in increased degradation rate as it is increased. The transformation path of these drugs consisted mainly of halogenations, hydroxylations and dealkylations. After several days of reaction two derivatives remained stable for phenazone: chloro-hydroxy-phenazone and N-demethyl-chloro-hydroxy-phenazone and two for propyphenazone: N-demethyl-hydroxy-propyphenazone and N-demethyl-chloro-hydroxy-propyphenazone. Moreover, experiments conducted with real water matrices, tap and surface water, showed that reaction, and formation of by-products, can take place both at the emission source point (household) and during drinking water production. PMID:22381982

  19. Bio-inspired Design of Electrocatalysts for Oxalate Oxidation: a Combined Experimental and Computational Study of Mn–N–C Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Matanovic, Ivana; Babanova, Sofia; Perry, Albert; Serov, Alexey; Artyushkova, Kateryna; Atanassov, Plamen

    2015-05-28

    We report a novel non-platinum group metal (non-PGM) catalyst derived from Mn and amino- antipyrine (MnAAPyr) that shows electrochemical activity towards the oxidation of oxalic acid comparable to Pt with an onset potential for oxalate oxidation measured to be 0.714 * 0.002 V vs. SHE at pH = 4. The material has been synthesized using a templating Sacrificial Support Method with manganese nitrate and 4-aminoantipyrine as precursors. This catalyst is a nano-structured material in which Mn is atomically dispersed on a nitrogendoped graphene matrix. XPS studies reveal high abundance of pyridinic, Mn–Nx, and pyrrolic nitrogen pointing towards the conclusion that pyridinic nitrogen atoms coordinated to manganese constitute the active centers. Thus, the main features of the MnAAPyr catalyst are it exhibits similarity to the active sites of naturally occurring enzymes that are capable of efficient and selective oxidation of oxalic acid. Density functional theory in plane wave formalism with Perdew, Burke and Ernzerhof functional was further used to study the stability and activity of different one-metal active centers that could exist in the catalyst. The results show that the stability of the Mn–Nx sites changes in the following order: MnN4 4 MnN3C 4 MnN2C2 4 MnN3. Based on the overpotentials of 0.64 V and 0.71 V vs. SHE, calculated using the free energy diagrams for the oxalate oxidation mechanism, we could conclude that the MnN3C and MnN2C2 sites are most probable Mn–Nx sites responsible for the reported catalytic activity of the new catalyst.

  20. 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

  1. 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.

  2. 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. PMID:27585929

  3. Simultaneous measurement of blood flow and glucose metabolism by autoradiographic techniques

    International Nuclear Information System (INIS)

    A double tracer autoradiographic technique using 131I-iodo-antipyrine and 14C-deoxyglucose is presented for the simultaneous measurement of blood flow and cerebral glucose utilization in the same animal. 131I is a gamma emitting isotope with a half life of 8.06 days and can be detected with adequate resolution on standard autoradiographic films. Autoradiograms are made before and after decay of 131I; the time interval between the 2 exposures and the concentration of the 2 tracers is adjusted to avoid significant cross-contamination. In this way, 2 film exposures are obtained which can be processed quantitatively like single tracer autoradiograms. The validity of the method for the investigation of local coupling of flow and metabolism was tested under various physiological and pathophysiological conditions. Coupling was tight in barbiturate-anesthetized healthy animals, but not under halothane anesthesia where uncoupling occurred in various subcortical structures. Focal seizures induced by topical application of penicillin on the cortical surface led to a coupled increase of metabolism and flow in thalamic relay nuclei but not at the site of penicillin administration where increased glucose utilization was not accompanied by similar increase in blood flow. Both coupled and uncoupled increases in local glucose utilization were observed in spreading depression and in circumscribed areas of experimental brain tumors. The results obtained demonstrate that double tracer autoradiography allows allows the very precise local assessment of cerebral blood flow and glucose utilization, and, therefore, is particularly suited to the study of regional coupling processes under various experimental conditions

  4. Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

    Science.gov (United States)

    Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

    2016-01-01

    We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated. PMID:27581638

  5. Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor.

    Science.gov (United States)

    Xie, Feng; Chai, Jia-Ke; Hu, Quan; Yu, Yong-Hui; Ma, Li; Liu, Ling-Ying; Zhang, Xu-Long; Li, Bai-Ling; Zhang, Dong-Hai

    2016-06-30

    The aim of the present study was to investigate the potential application of (+)-camphor as a penetration enhancer for the transdermal delivery of drugs with differing lipophilicity. The skin irritation of camphor was evaluated by in vitro cytotoxicity assays and in vivo transdermal water loss (TEWL) measurements. A series of model drugs with a wide span of lipophilicity (logP value ranging from 3.80 to -0.95), namely indometacin, lidocaine, aspirin, antipyrine, tegafur and 5-fluorouracil, were tested using in vitro transdermal permeation experiments to assess the penetration-enhancing profile of camphor. Meanwhile, the in vivo skin microdialysis was carried out to further investigate the enhancing effect of camphor on the lipophilic and hydrophilic model drugs (i.e. lidocaine and tegafur). SC (stratum corneum)/vehicle partition coefficient and Fourier transform infrared spectroscopy (FTIR) were performed to probe the regulation action of camphor in the skin permeability barrier. It was found that camphor produced a relatively low skin irritation, compared with the frequently-used and standard penetration enhancer laurocapram. In vitro skin permeation studies showed that camphor could significantly facilitate the transdermal absorption of model drugs with differing lipophilicity, and the penetration-enhancing activities were in a parabola curve going downwards with the drug logP values, which displayed the optimal penetration-enhancing efficiency for the weak lipophilic or hydrophilic drugs (an estimated logP value of 0). In vivo skin microdialysis showed that camphor had a similar penetration behavior on transdermal absorption of model drugs. Meanwhile, the partition of lipophilic drugs into SC was increased after treatment with camphor, and camphor also produced a shift of CH2 vibration of SC lipid to higher wavenumbers and decreased the peak area of the CH2 vibration, probably resulting in the alteration of the skin permeability barrier. This suggests that

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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. PMID:26206403

  11. Pharmacokinetic drug interactions of macrolides.

    Science.gov (United States)

    Periti, P; Mazzei, T; Mini, E; Novelli, A

    1992-08-01

    , carbamazepine, phenazone (antipyrine) and triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in those taking oral contraceptives. Erythromycin and its different prodrugs appear to be less potent inhibitors of drug metabolism. Case reports and controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide and bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these compounds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined administration should be carried out only with careful patient monitoring.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1511528

  12. Late radiation damage in bone, bone marrow and brain vasculature, with particular emphasis upon fractionation models

    International Nuclear Information System (INIS)

    X-ray induced changes in rat and human bone and bone marrow vasculature and in rat brain vasculature were measured as a function of time after irradiation and absorbed dose. The absorbed dose in the organ varied from 5 to 25 Gy for single dose irradiations and from 19 to 58 Gy for fractionated irradiations.The number of fractions varied from 3 to 10 for the rats and from 12 to 25 for the human. Blood flow changes were measured using an ''1''2''5I antipyrine or ''8''6RbCl extraction technique. The red blood cell (RBC) volume was examined by ''5''1Cr labelled red cells. Different fractionation models have been compared. Radiation induced reduction of bone and bone marrow blood flow were both time and dose dependent. Reduced blood flow 3 months after irradiation would seem to be an important factor in the subsequent atrophy of bones. With a single dose of 10 Gy the bone marrow blood flow returned to the control level by 7 months after irradiation. In the irradiated bone the RBC volume was about same as that in the control side but in bone marrow the reduction was from 32 to 59%. The dose levels predicted by the nominal standard dose (NSD) formula produced about the same damage to the rat femur seven months after irradiation when the extraction of ''8''6Rb chloride and the dry weight were concerned as the end points. However, the results suggest that the NSB formula underestimates the late radiation damage in bone marrow when a small number of large fractions are used. In the irradiated brains of the rats the blood flow was on average 20.4% higher compared to that in the control group. There was no significant difference in brain blood flow between different fractionation schemes. The value of 0.42 for the exponent of N corresponds to the average value for central nervous system tolerance in the literature. The model used may be sufficiently accurate for clinical work provided the treatment schemes used do not depart too radically from standard practice

  13. Analysis of the photo catalytic degradation of the 4-chloro phenol and endosulfan by gas chromatography

    International Nuclear Information System (INIS)

    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 TiO2 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)

  14. 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%.

  15. 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

  16. 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

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    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.