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Sample records for albendazole sulfoxide enantiomers

  1. Comparative hepatic and extrahepatic enantioselective sulfoxidation of albendazole and fenbendazole in sheep and cattle.

    PubMed

    Virkel, G; Lifschitz, A; Sallovitz, J; Pis, A; Lanusse, C

    2004-05-01

    The enantioselective sulfoxidation of the prochiral anthelmintic compounds albendazole (ABZ) and fenbendazole (FBZ) was investigated in liver, lung and small intestinal microsomes obtained from healthy sheep and cattle. The microsomal fractions were incubated with a 40 microM concentration of either ABZ or FBZ. Inhibition of the flavin-containing monooxygenase (FMO) system was carried out by preincubation with 100 microM methimazole (MTZ) either with or without heat pretreatment (2 min at 50 degrees C). ABZ and FBZ were metabolized to the (+) and (-) enantiomers of their sulfoxide metabolites, named albendazole sulfoxide (ABZSO) and oxfendazole (OFZ), respectively. ABZ sulfoxidation rates were higher (p < 0.001) than those observed for FBZ. The FMO-mediated liver sulfoxidation of ABZ was enantioselective (100%) toward the (+) ABZSO production in both species. Liver sulfoxidation of FBZ by FMO was also enantioselective toward (+) OFZ (sheep = 65%; cattle = 79%). Cytochrome P450 was found to be mainly involved in the production of (-) ABZSO in the liver. MTZ did not affect the sulfoxidation of ABZ by lung microsomes, which may indicate that FMO is not involved in the production of ABZSO in this tissue. A significant (p < 0.05) inhibition of (-) ABZSO production by liver microsomes was observed after ABZ incubation in the presence of erythromycin (cattle = 21%) and ketoconazole (sheep = 36%). Both CYP3A substrates induced a reduction in the production of (-) ABZSO (sheep = 67-78%, cattle = 50-78%) by lung microsomes. Overall, the results reported here contribute to the identification of the metabolic pathways involved in the biotransformation of benzimidazole anthelmintics extensively used for parasite control in ruminants.

  2. A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis.

    PubMed

    González-Hernández, Iliana; Ruiz-Olmedo, María Isabel; Cárdenas, Graciela; Jung-Cook, Helgi

    2012-02-01

    The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.

  3. Enantiomeric behaviour of albendazole and fenbendazole sulfoxides in domestic animals: pharmacological implications.

    PubMed

    Capece, Bettencourt P S; Virkel, Guillermo L; Lanusse, Carlos E

    2009-09-01

    Albendazole and fenbendazole are methylcarbamate benzimidazole anthelmintics extensively used to control gastrointestinal parasites in domestic animals. These parent compounds are metabolised to albendazole sulfoxide and fenbendazole sulfoxide (oxfendazole), respectively. Both sulfoxide derivatives are anthelmintically active and are manufactured for use in animals. They metabolites have an asymmetric centre on their chemical structures and two enantiomeric forms of each sulfoxide have been identified in plasma, tissues of parasite location and within target helminths. Both the flavin-monooxygenase and cytochrome P450 systems are involved in the enantioselective biotransformation of these anthelmintic compounds in ruminant species. A relevant progress on the understanding of the relationship among enantioselective metabolism and systemic availability of each enantiomeric form has been achieved. This article reviews the current knowledge on the pharmacological implications of the enantiomeric behaviour of albendazole sulfoxide and oxfendazole in domestic animals.

  4. Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity.

    PubMed

    Capece, B P S; Navarro, M; Arcalis, T; Castells, G; Toribio, L; Perez, F; Carretero, A; Ruberte, J; Arboix, M; Cristòfol, C

    2003-05-01

    Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.

  5. Therapeutic monitoring of albendazole: a high-performance liquid chromatography method for determination of its active metabolite albendazole sulfoxide.

    PubMed

    Zeugin, T; Zysset, T; Cotting, J

    1990-03-01

    A sensitive and specific reversed-phase high-performance liquid chromatography (HPLC) method is described for the quantitative determination of albendazole sulfoxide (ASOX); since albendazole sulfone (ASON) appears only in small amounts and albendazole (ABZ) normally does not appear in human plasma, only a qualitative determination of ASON and ABZ was made in human plasma. Plasma samples were extracted three times using ethylacetate and petroleum benzine; this yielded optically clear samples which after evaporation were dissolved in the HPLC solvent and injected onto an RP-C18 column, with ultraviolet detection at 290 nm. The detection limit of the main metabolite ASOX was 50 nM and that of ASON was 100 nM. The intraday coefficient of variation for ASOX was 3.3% at a concentration of 2.2 microM, and the interday coefficients of variation were 14.5, 7.3, and 9.1% at ASOX concentrations of 0.5, 2.5, and 5.0 microM, respectively. Calibration was linear in a concentration range of 0.05-12 microM for ASOX and 0.1-8 microM for ASON, respectively. Pharmacokinetic data of a patient with echinococcosis are presented.

  6. Effect of the water content on the retention and enantioselectivity of albendazole and fenbendazole sulfoxides using amylose-based chiral stationary phases in organic-aqueous conditions.

    PubMed

    Materazzo, Sabrina; Carradori, Simone; Ferretti, Rosella; Gallinella, Bruno; Secci, Daniela; Cirilli, Roberto

    2014-01-31

    Four commercially available immobilized amylose-derived CSPs (Chiralpak IA-3, Chiralpak ID-3, Chiralpak IE-3 and Chiralpak IF-3) were used in the HPLC analysis of the chiral sulfoxides albendazole (ABZ-SO) and fenbendazole (FBZ-SO) and their in vivo sulfide precursor (ABZ and FBZ) and sulfone metabolite (ABZ-SO2 and FBZ-SO2) under organic-aqueous mode. U-shape retention maps, established by varying the water content in the acetonitrile- and ethanol-water mobile phases, were indicative of two retention mechanisms operating on the same CSP. The dual retention behavior of polysaccharide-based CSPs was exploited to design greener enantioselective and chemoselective separations in a short time frame. The enantiomers of ABZ-SO and FBZ-SO were baseline resolved with water-rich mobile phases (with the main component usually being 50-65% water in acetonitrile) on the IF-3 CSP and ethanol-water 100:5 mixture on the IA-3 and IE-3 CSPs. A simultaneous separation of ABZ (or FBZ), enantiomers of the corresponding sulfoxide and sulfone was achieved on the IA-3 using ethanol-water 100:60 (acetonitrile-water 100:100 for FBZ) as a mobile phase.

  7. Pharmacokinetic behaviour of albendazole sulphoxide enantiomers in male and female sheep.

    PubMed

    Capece, B P; Castells, G; Pérez, F; Arboix, M; Cristòfol, C

    2000-07-01

    Benzimidazole anthelmintic drugs are widely used in veterinary practice. Albendazole sulphoxide (ABZSO) is a benzimidazole drug with two enantiomers, as a consequence of a chiral centre in the sulphoxide group. The kinetics of these enantiomers were studied in male and female sheep. Plasma samples were obtained from the animals between 0.5 and 72 h after oral administration of 7.5 mg/kg of a racemic formulation of ABZSO (total-ABZSO). After a liquid-liquid extraction, the samples were analysed by HPLC to determine the concentrations of total-ABZSO and of the sulphone metabolite (ABZSO2). During the chromatographic analysis, the ABZSO peak was collected and reanalysed by an HPLC technique using a Chiral AGP column to quantify the enantiomeric proportion therein. After kinetic analysis, the AUCs obtained for the (+)-ABZSO were 5.8 and 4.0 times higher than those for the (-)-ABZSO in male and female animals, respectively. The mean residence times were 23.4 and 16.1 h for (+)-ABZSO and 22.2 and 17.4 h for (-)-ABZSO for male and female animals, respectively. The only significant difference between the sexes (p < 0.05) was in the Tmax of the (-)-ABZSO. Comparing both enantiomers within each sex, significant differences were found in all the kinetic parameters. Finally, no kinetic differences were found between sex for total-ABZSO or ABZSO2.

  8. A simple assay for the simultaneous determination of human plasma albendazole and albendazole sulfoxide levels by high performance liquid chromatography in tandem mass spectrometry with solid-phase extraction.

    PubMed

    Wojnicz, Aneta; Cabaleiro-Ocampo, Teresa; Román-Martínez, Manuel; Ochoa-Mazarro, Dolores; Abad-Santos, Francisco; Ruiz-Nuño, Ana

    2013-11-15

    A simple, reproducible and fast (4 min chromatogram) method of liquid chromatography in tandem with mass spectrometry (LC/MS-MS) was developed to determine simultaneously the plasma levels of albendazole (ABZ) and its metabolite albendazole sulfoxide (ABZOX) for pharmacokinetic and clinical analysis. Each plasma sample was extracted by solid phase extraction (SPE) using phenacetin as internal standard (IS). The extracted sample was eluted with a Zorbax XDB-CN column using an isocratic method. The mobile phase consisting of water with 1% acetic acid (40%, A) and MeOH (60%, B), was used at a flow rate of 1 mL/min. ABZ and ABZOX were detected and identified by mass spectrometry with electrospray ionization (ESI) in the positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 5-1000 ng/mL for ABZ and 10-1500 ng/mL (full validation) or 10-5000 ng/mL (partial validation) for ABZOX, with 5 and 10 ng/mL lower limit of quantification (LLOQ) for ABZ and ABZOX, respectively. The tests of accuracy and precision, matrix effect, extraction recovery and stability of the samples for both ABZ and ABZOX did not deviate more than 20% for the LLOQ and no more than 15% for other quality controls (QCs), according to regulatory agencies.

  9. The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide via achiral, gravity-driven column chromatography: a case study.

    PubMed

    Wzorek, Alicja; Klika, Karel D; Drabowicz, Józef; Sato, Azusa; Aceña, José Luis; Soloshonok, Vadim A

    2014-07-14

    This work explores the self-disproportionation of enantiomers (SDE) of chiral sulfoxides via achiral, gravity-driven column chromatography using methyl n-pentyl sulfoxide as a case study. A major finding of this work is the remarkable persistence and high magnitude of the SDE for the analyte. Thus, it is the first case where SDE is observed even in the presence of MeOH in the mobile phase. The study demonstrated the practical preparation, in line with theory, of enantiomerically pure (>99.9% ee) samples of methyl n-pentyl sulfoxide starting from a sample of only modest ee (<35%). Remarkably, it was found that the order of elution was inverted, i.e. enantiomerically depleted fractions preceded later eluting enantiomerically enriched ones, when the stationary phase was changed from silica gel to aluminum oxide. To the best of our knowledge, this is the first occurrence of inverted SDE behavior due solely to a change in the stationary phase. Aberrant SDE behavior was observed in that the ee did not always fall continuously during the progression of the chromatography, and this was attributed to the complexity of the system at hand which cannot be described in simple terms such as the formation only of homo- and heterochiral dimers based on a single interaction. The results nevertheless suggest that all compounds with a chiral sulfoxide moiety in their structure are likely to exhibit the SDE phenomenon and thus this work constitutes the first example of SDE predictability. Moreover, it could well be that optical purification based on the SDE phenomenon is a simple, convenient, and inexpensive method for the optical purification of this class of compounds with a high degree of proficiency.

  10. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    ERIC Educational Resources Information Center

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  11. The Effect of Protein Restriction in the In Vitro Metabolism of Albendazole in Rats.

    PubMed

    Belaz, Kátia Roberta A; de O Cardoso, Josiane; da Silva, Carlos Alberto; Oliveira, Regina V

    2015-01-01

    This work presents an in vitro investigation of the effect of protein restriction on the metabolism of albendazole (ABZ). This study was conducted using liver microsomal fractions obtained from Wistar rats. For the quantitative analysis, a multidimensional High Performance Liquid Chromatography (2D HPLC) method was fully validated for the determination of the ABZ metabolites: albendazole sulfoxide, albendazole sulfone and albendazole 2-aminesulfone. The target compounds were directly extracted using a C8-RAM-BSA column (5.0x0.46 cm i.d.) and analyzed on a chromatographic chiral column containing amylose tris(3,5-dimethylphenylcarbamate) (150x4.6 mm i.d.). The in vitro biotransformation results showed that the protein restriction influenced the oxidative metabolism of ABZ. The production of R-(+)-ABZ-SO (1309 nmol/L) and S-(-)-ABZ-SO (1456 nmol/L) was higher in the control animals than in the animals fed with a diet containing 6% protein, which produced 778.7 nmol/L and 709.5 nmol/L for R-(+) and S-(-)-ABZ-SO enantiomers, respectively. These results were statistically inspected by Student´s t test and the results showed a significant difference between the two means (p<0.05). Moreover, the production of ABZ-SO enantiomers was enantioselective where the S-(-)-ABZ-SO was formed in greater amounts than the R-(+)-ABZ-SO in control animals (p=0.0231). However, the enantioselectivity was not observed when the in vitro biotransformation of ABZ was conducted using the microsomal fractions obtained from protein restriction animals (p>0.05). Furthermore, animal nutritional condition could affect the pattern of ABZ sulphoxidation indicating that the protein nutrition affect primarily the formation of R-(+)-ABZSO and S-(-)-ABZ-SO enantiomers.

  12. The sodium salt of the enantiomers of ricobendazole: Preparation, solubility and chiroptical properties.

    PubMed

    Cirilli, Roberto; Guglielmi, Paolo; Formica, Francesca Romana; Casulli, Adriano; Carradori, Simone

    2017-02-20

    Albendazole (ABZ) is a sulfanyl-benzimidazole anthelmintic drug used worldwide in the treatment and prevention of parasitic diseases in animals and humans. Following oral administration, ABZ is rapidly oxidized into the pharmacologically active chiral sulfoxide metabolite known as ricobendazole (RBZ). As its achiral precursor, RBZ shows very low intestinal absorption due to its poor solubility in water (0.06mgmL(-1)). To the best of our knowledge, there is no known example in human medicine of a water-soluble salt form of racemic or enantiomerically pure RBZ. In the present study, we describe in detail the preparation of the sodium (Na) salt of the enantiomers of RBZ through a two-step process: i) the multi-milligram resolution of RBZ by HPLC on the amylose-based Chiralpak IG chiral stationary phase under polar organic mode; ii) the salification of the isolated enantiomers of RBZ by reaction with sodium hydroxide solution. The spectroscopic and chiroptical properties of the RBZ-Na enantiomers were determined. Due to their unique solubility in 0.01M phosphate buffer at physiological pH (14.49mgmL(-1)) and the high sample throughput obtained on semipreparative separation of the non-salified form, it is potentially possible to develop new anthelmintic enantiopure formulations with improved pharmacokinetic properties and lower toxicity.

  13. Dimethyl Sulfoxide

    PubMed Central

    Capriotti, Joseph A.

    2012-01-01

    Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology. PMID:23050031

  14. Albendazole treatment of echinococcosis in humans: effects on microsomal metabolism and drug tolerance.

    PubMed

    Steiger, U; Cotting, J; Reichen, J

    1990-03-01

    We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An aminopyrine breath test was performed in 12 patients while they were receiving albendazole treatment and while they were not. Excretion of 14CO2 in breath averaged 0.70%.kg.mmol-1 +/- 0.20%.kg.mmol-1 without treatment and 0.54%.kg.mmol-1 +/- 0.14%.kg.mmol-1 with treatment (p less than 0.005). Plasma levels of albendazole sulfoxide were measured 4 hours after the morning dose during the first and second half of the 4-week treatment cycles. In nine of the 12 patients albendazole sulfoxide levels decreased during the second half of the cycle by an average of 0.84 +/- 0.76 mumol/L (p less than 0.02). Transaminase levels increased in 10 of the 12 patients during long-term albendazole treatment, and major side effects, including hepatotoxicity, neutropenia, and alopecia, were observed in three patients. We conclude that albendazole partially inhibits microsomal enzyme function but induces its own metabolism. Hepatotoxicity and other possible severe side effects necessitate close therapeutic monitoring of patients who are given albendazole.

  15. Effect of nitazoxanide on albendazole pharmacokinetics in cerebrospinal fluid and plasma in rats.

    PubMed

    Ruiz-Olmedo, María Isabel; González-Hernández, Iliana; Palomares-Alonso, Francisca; Franco-Pérez, Javier; González F, María de Lourdes; Jung-Cook, Helgi

    2017-03-01

    Background: Although albendazole is the drug-of-choice for the treatment of neurocysticercosis, its efficacy is limited due to its low bioavailability. An alternative for optimizing pharmacological treatment is through drug combinations. In vitro studies have shown that nitazoxanide and tizoxanide (the active metabolite of nitazoxanide) exhibit cysticidal activity and that the combination of tizoxanide with albendazole sulfoxide (the active metabolite of albendazole) produced an additive effect. Objectives: (1) To assess the concentration profile of tizoxanide in plasma and in cerebrospinal fluid; and (2) to evaluate the influence of nitazoxanide on the pharmacokinetics of albendazole in plasma and in cerebrospinal fluid. Methods: Two different studies were conducted. In study 1, 10 male Sprague-Dawley rats received a single oral dose of 7.5 mg/kg of nitazoxanide and serial blood and cerebrospinal fluid samples were collected over a period of 4 h. In study 2, 38 healthy male Sprague-Dawley rats were randomly divided into two groups: one of these received a single dose of albendazole (15 mg/kg) and, in the other group, albendazole (15 mg/kg) was co-administered with nitazoxanide (7.5 mg/kg). Plasma and cerebrospinal fluid samples were collected from 0 to 16 h after administration. Albendazole sulfoxide and tizoxanide levels were assayed by using HPLC or LC/MS techniques. Results: In study 1, tizoxanide reached a maximum plasma concentration of 244.42 ± 31.98 ng/mL at 0.25 h; however, in cerebrospinal fluid, this could be detected only at 0.5 h, and levels were below the quantification limit (10 ng/mL). These data indicate low permeation of tizoxanide into the blood brain barrier. In study 2, Cmax, the area under the curve, and the mean residence time of albendazole sulfoxide in plasma and cerebrospinal fluid were not affected by co-administration with nitazoxanide. Conclusion: The results of the present study indicate that in rats at the applied doses

  16. Albendazole-related drug residues in milk and their fate during cheesemaking, ripening, and storage.

    PubMed

    Fletouris, D J; Botsoglou, N A; Psomas, I E; Mantis, A I

    1998-11-01

    The level and nature of the albendazole residues in milk of treated cows were determined as a function of the time of milking (12-h intervals), and the fate of those residues during cheesemaking, ripening, and storage was examined when the obtained milk was used for making Teleme cheese. Ion-pair liquid chromatographic analysis with fluorescence detection showed that the albendazole sulfoxide metabolite reached its maximum (523 +/- 199 micrograms/kg) at the 1st milking and declined below the detection limit by the 4th milking. The sulfone metabolite attained its highest level (812 +/- 99 micrograms/kg) more slowly (at the 2nd milking) and declined below detection limit by the 13th milking. The 2-aminosulfone metabolite, which was present in the milk obtained at the 1st milking, reached its maximum (128 +/- 36 micrograms/kg) at the 3rd milking, and slowly declined to a level below detection limit by the 15th milking. Whey and cheese analysis revealed that about 70% of each major metabolite initially present in milk could be distributed in the whey. The remaining 30% occurred in the cheese at residue levels higher than those initially present in the milk of the 1st or 2nd milking (688 versus 445 or 450 versus 230 micrograms/kg for albendazole sulfoxide; 890 versus 608 or 1502 versus 783 micrograms/kg for albendazole sulfone; 19 versus 15 or 161 versus 105 micrograms/kg for albendazole 2-aminosulfone). Ripening and storage of the cheeses made from milks from the 1st or 2nd milkings results in a decrease of the sulfoxide metabolite (to 225 or 206 micrograms/kg), an increase of the sulfone metabolite (to 1,181 or 1,893 micrograms/kg), and no effect on the 2-aminosulfone metabolite.

  17. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

    PubMed Central

    Garcia, Hector H; Lescano, Andres G; Lanchote, Vera L; Pretell, E Javier; Gonzales, Isidro; Bustos, Javier A; Takayanagui, Osvaldo M; Bonato, Pierina S; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H

    2011-01-01

    AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. PMID:21332573

  18. Triclabendazole Sulfoxide Causes Stage-Dependent Embryolethality in Zebrafish and Mouse In Vitro

    PubMed Central

    Boix, Nuria; Teixido, Elisabet; Vila-Cejudo, Marta; Ortiz, Pedro; Ibáñez, Elena; Llobet, Juan M.; Barenys, Marta

    2015-01-01

    Background Fascioliasis and paragonimiasis are widespread foodborne trematode diseases, affecting millions of people in more than 75 countries. The treatment of choice for these parasitic diseases is based on triclabendazole, a benzimidazole derivative which has been suggested as a promising drug to treat pregnant women and children. However, at the moment, this drug is not approved for human use in most countries. Its potential adverse effects on embryonic development have been scarcely studied, and it has not been assigned a pregnancy category by the FDA. Thus, to help in the process of risk-benefit decision making upon triclabendazole treatment during pregnancy, a better characterization of its risks during gestation is needed. Methodology The zebrafish embryo test, a preimplantation and a postimplantation rodent whole embryo culture were used to investigate the potential embryotoxicity/teratogenicity of triclabendazole and its first metabolite triclabendazole sulfoxide. Albendazole and albendazole sulfoxide were included as positive controls. Principal Findings Triclabendazole was between 10 and 250 times less potent than albendazole in inducing dysmorphogenic effects in zebrafish or postimplantation rodent embryos, respectively. However, during the preimplantation period, both compounds, triclabendazole and triclabendazole sulfoxide, induced a dose-dependent embryolethal effect after only 24 h of exposure in rodent embryos and zebrafish (lowest observed adverse effect concentrations = 10 μM). Conclusions/Significance In humans, after ingestion of the recommended doses of triclabendazole to treat fascioliasis and paragonimiasis (10 mg/kg), the main compound found in plasma is triclabendazole sulfoxide (maximum concentration 38.6 μM), while triclabendazole concentrations are approximately 30 times lower (1.16 μM). From our results it can be concluded that triclabendazole, at concentrations of the same order of magnitude as the clinically relevant ones, does

  19. Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs.

    PubMed

    Gokbulut, C; Bilgili, A; Hanedan, B; McKellar, Q A

    2007-09-30

    The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.

  20. Enantioselective distribution of albendazole metabolites in cerebrospinal fluid of patients with neurocysticercosis

    PubMed Central

    Takayanagui, O M; Bonato, P S; Dreossi, S A C; Lanchote, V L

    2002-01-01

    Aims Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ undergoes extensive metabolism to (+) and (−)-albendazole sulphoxide (ASOX), which are further metabolized to albendazole sulphone (ASON). We have investigated the distribution of (+)-ASOX (−)-ASOX, and ASON in cerebrospinal fluid (CSF) of patients with neurocysticercosis. Methods Twelve patients with a diagnosis of active brain parenchymal neurocysticercosis treated with albendazole for 8 days (15 mg kg−1 day−1) were investigated. On day 8, serial blood samples were collected during the dose interval (0–12 h) and one CSF sample was taken from each patient by lumbar puncture at different time points up to 12 h after the last albendazole dose. Albendazole metabolites were determined in CSF and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence detection. Population curves for CSF albendazole metabolite concentration vs time were constructed. Results The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3) for (+)-ASOX and 2.7 (95% CI: 1.8, 3.7) for (−)-ASOX, with the two-tailed P value of 0.9873 being non-significant. These data indicate that the transport of ASOX through the blood–brain barrier is not enantioselective, but rather depends on passive diffusion. The present results suggest the accumulation of the (+)-ASOX metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(−) ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half-life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant metabolite in the CSF compared with ASON; the CSF AUCASOX/AUCASON ratio was approximately 20 and the elimination half-life of ASON in CSF was 2.6 h. Conclusions We have demonstrated accumulation of the (+)-ASOX metabolite in CSF, which was about three times greater than the (−) antipode. ASOX concentrations were approximately 20 times higher than those observed for the ASON metabolite. PMID:12207631

  1. Albendazole treatment in human taeniasis.

    PubMed

    de Kaminsky, R G

    1991-01-01

    The results are presented of albendazole trials on human taeniasis infections in Honduras, involving 56 of 68 individuals (2% of the inhabitants) found to be infected during surveys conducted in 15 rural communities. Of the 3 methods used for diagnosis of infection, the Kato cellophane thick smear showed 80% reliability, a combination of Kato and 'Scotch' tape perianal swab 88%, and clinical history of proglottid expulsion less than 50%. Individuals were treated with a dose of 400 mg of albendazole per day for 3 d, followed for 5 d to verify tapeworm expulsion, and evaluated again at 60 and 90 d to assess drug efficacy. All 56 treated individuals remained stool-negative after 60 and 90 d; a partial strobila or segments were recovered from 21 of them (37.5%). Of these, Taenia saginata was identified from 4, and T. solium from 15; 2 specimens could not be specifically identified. Based on negative stool examinations and clinical history after 60 and 90 d, albendazole seems to be a well tolerated, very effective drug for treating infections with Taenia spp. However, confirmation of these results is needed due to the difficulty of making a reliable diagnosis of such infections.

  2. Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test.

    PubMed

    Mattsson, Anna; Ullerås, Erik; Patring, Johan; Oskarsson, Agneta

    2012-08-01

    The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.

  3. Albendazole in the treatment of pulmonary echinococcosis.

    PubMed Central

    Aggarwal, P; Wali, J P

    1991-01-01

    Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid disease were treated with albendazole 10 mg/kg/day for eight weeks. None of the 10 patients showed any radiological or serological improvement with this treatment regimen. Albendazole in these doses appears to have little role in the treatment of pulmonary hydatid disease. PMID:1926033

  4. Albendazole

    MedlinePlus

    ... to treat neurocysticercosis (infection caused by the pork tapeworm in the muscles, brain, and eyes that may ... cystic hydatid disease (infection caused by the dog tapeworm in the liver, lung, and lining of the ...

  5. p-Chlorophenyl methyl sulfoxide

    Integrated Risk Information System (IRIS)

    p - Chlorophenyl methyl sulfoxide ; CASRN 934 - 73 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  6. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  7. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  8. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  9. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  10. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  11. Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

    PubMed Central

    Lima, Renata Monteiro; Ferreira, Maria Augusta Drago; de Jesus Ponte Carvalho, Teresa Maria; Dumêt Fernandes, Bruno José; Takayanagui, Osvaldo Massaiti; Garcia, Hector Hugo; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

    2011-01-01

    AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. PMID:21395645

  12. Structural changes by sulfoxidation of phenothiazine drugs

    NASA Astrophysics Data System (ADS)

    Dahl, Svein G.; Kollman, Peter A.; Rao, Shashidhar N.; Singh, U. Chandra

    1992-06-01

    The side-chain conformations of psychoactive phenothiazine drugs in crystals are different from those of biologically inactive ring sulfoxide metabolites. This study examines the potential energies, molecular conformations and electrostatic potentials in chlorpromazine, levomepromazine (methotrimeprazine), their sulfoxide metabolites and methoxypromazine. The purpose of the study was to examine the significance of the different crystal conformations of active and inactive phenothiazine derivatives, and to determine why phenothiazine drugs lose most of their biological activity by sulfoxidation. Quantum mechanics and molecular mechanics calculations demonstrated that conformations with the side chain folded over the ring structure had lowest potential energy in vacuo, both in the drugs and in the sulfoxide metabolites. In the sulfoxides, side chain conformations corresponding to the crystal structure of chlorpromazine sulfoxide were characterized by stronger negative electrostatic potentials around the ring system than in the parent drugs. This may weaken the electrostatic interaction of sulfoxide metabolites with negatively charged domains in dopamine receptors, and cause the sulfoxides to be virtually inactive in dopamine receptor binding and related pharmacological tests.

  13. Enantiopure sulfoxides: recent applications in asymmetric synthesis.

    PubMed

    Carreño, M Carmen; Hernández-Torres, Gloria; Ribagorda, María; Urbano, Antonio

    2009-11-07

    Sulfoxides are nowadays recognised as powerful chiral auxiliaries that may participate in a wide range of asymmetric reactions. Their high configurational stability, the existence of several efficient methods allowing the access to both configurations as well as their synthetic versatility are characteristic features offering a tremendous potential to develop new applications. Significant recent advances leading to high asymmetric inductions in carbon-carbon and carbon-oxygen bond forming reactions, and applications of homochiral sulfoxides to atroposelective synthesis and asymmetric catalysis are discussed. New uses of sulfoxides in the design of chiroptical switches are also shown.

  14. Cetirizine and albendazole induced dystonia in a child.

    PubMed

    Yılmaz-Topa, Özge; Tuygun, Nilden; Akça, Halise; Polat, Emine; Karacan, Can Demir

    2015-01-01

    Drug-induced dystonic reactions are a common presentation to the Pediatric Emergency Department frequently with antiemetics, antidepressants, dopamineblocking agents and antipyschotics. We report a case of generalized form of dystonia after taking albendazole and cetirizine. There is only one case with albendazole induced and two cases with cetirizine induced dystonia in the literature.

  15. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...

  16. Respiratory Toxicity of Dimethyl Sulfoxide.

    PubMed

    Takeda, Kotaro; Pokorski, Mieczyslaw; Sato, Yutaka; Oyamada, Yoshitaka; Okada, Yasumasa

    2016-01-01

    Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents for hydrophobic substances in biological experiments. In addition, the compound exhibits a plethora of bioactivities, which makes it of potential pharmacological use of its own. The influence on respiration, and thus on arterial blood oxygenation, of DMSO is unclear, contentious, and an area of limited study. Thus, in the present investigation we set out to determine the influence on lung ventilation of cumulated doses of DMSO in the amount of 0.5, 1.5, 3.5, 7.5, and 15.5 g/kg; each dose given intraperitoneally at 1 h interval in conscious mice. Ventilation and its responses to 7 % hypoxia (N(2) balanced) were recorded in a whole body plethsymograph. We demonstrate a dose-dependent inhibitory effect of DMSO on lung ventilation and its hypoxic responsiveness, driven mostly by changes in the tidal component. The maximum safe dose of DMSO devoid of meaningful consequences for respiratory function was 3.5 g/kg. The dose of 7.5 g/kg of DMSO significantly dampened respiration, with yet well preserved hyperventilatory response to hypoxia. The highest dose of 15.5 g/kg severely impaired ventilation and its responses. The study delineates the safety profile of DMSO regarding the respiratory function which is essential for maintaining proper tissue oxygenation. Caution should be exercised concerning dose concentration of DMSO.

  17. Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole.

    PubMed

    Hengsawas Surasarang, Soraya; Keen, Justin M; Huang, Siyuan; Zhang, Feng; McGinity, James W; Williams, Robert O

    2017-05-01

    The purpose of this study was to enhance the dissolution properties of albendazole (ABZ) by the use of amorphous solid dispersions. Phase diagrams of ABZ-polymer binary mixtures generated from Flory-Huggins theory were used to assess miscibility and processability. Forced degradation studies showed that ABZ degraded upon exposure to hydrogen peroxide and 1 N NaOH at 80 °C for 5 min, and the degradants were albendazole sulfoxide (ABZSX), and ABZ impurity A, respectively. ABZ was chemically stable following exposure to 1 N HCl at 80 °C for one hour. Thermal degradation profiles show that ABZ, with and without Kollidon(®) VA 64, degraded at 180 °C and 140 °C, respectively, which indicated that ABZ could likely be processed by thermal processing. Following hot melt extrusion, ABZ degraded up to 97.4%, while the amorphous ABZ solid dispersion was successfully prepared by spray drying. Spray-dried ABZ formulations using various types of acids (methanesulfonic acid, sulfuric acid and hydrochloric acid) and polymers (Kollidon(®) VA 64, Soluplus(®) and Eudragit(®) E PO) were studied. The spray-dried ABZ with methanesulfonic acid and Kollidon(®) VA 64 substantially improved non-sink dissolution in acidic media as compared to bulk ABZ (8-fold), physical mixture of ABZ:Kollidon(®) VA 64 (5.6-fold) and ABZ mesylate salt (1.6-fold). No degradation was observed in the spray-dried product for up to six months and less than 5% after one-year storage. In conclusion, amorphous ABZ solid dispersions in combination with an acid and polymer can be prepared by spray drying to enhance dissolution and shelf-stability, whereas those made by melt extrusion are degraded.

  18. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

    PubMed Central

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  19. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems.

    PubMed

    Wu, Zhexue; Lee, Doohyun; Joo, Jeongmin; Shin, Jung-Hoon; Kang, Wonku; Oh, Sangtaek; Lee, Do Yup; Lee, Su-Jun; Yea, Sung Su; Lee, Hye Suk; Lee, Taeho; Liu, Kwang-Hyeon

    2013-11-01

    Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite formation have not been identified. In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in the formation of hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole, respectively. Of the 10 recombinant P450s, CYP2J2 and/or CYP2C19 was the predominant enzyme catalyzing the hydroxylation of albendazole and fenbendazole. Albendazole hydroxylation to hydroxyalbendazole is primarily mediated by CYP2J2 (0.34 μl/min/pmol P450, which is a rate 3.9- and 8.1-fold higher than the rates for CYP2C19 and CYP2E1, respectively), whereas CYP2C19 and CYP2J2 contributed to the formation of hydroxyfenbendazole from fenbendazole (2.68 and 1.94 μl/min/pmol P450 for CYP2C19 and CYP2J2, respectively, which are rates 11.7- and 8.4-fold higher than the rate for CYP2D6). Correlation analysis between the known P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole formation in samples from 14 human liver microsomes showed that albendazole hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation correlates with CYP2C19 and CYP2J2 activities. These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. In conclusion, our data for the first time suggest that albendazole hydroxylation is primarily catalyzed by CYP2J2, whereas fenbendazole hydroxylation is preferentially catalyzed by CYP2C19 and CYP2J2. The present data will be useful in understanding the pharmacokinetics and drug interactions of albendazole and fenbendazole in vivo.

  20. Sex differences in the disposition of albendazole metabolites in sheep.

    PubMed

    Cristòfol, C; Navarro, M; Franquelo, C; Valladares, J E; Arboix, M

    1998-08-14

    Sex differences in the disposition of albendazole metabolites in sheep after oral administration of 20 mg/kg of netobimin have been studied. Some kinetic parameters of both metabolites show statistical differences between sexes; the sulphoxide and sulphone t1/2beta and MRT were lower in male animals than in females. Peak concentrations and AUC of sulphone metabolites were higher in males suggesting a greater oxidation rate compared with females. Urine excretion of albendazole metabolites, sulphoxide, sulphone, and amino sulphone appeared to be greater in female sheep than in males, mainly the sulphoxide metabolite. These differences between sexes can be caused by male sexual hormones, because testosterone and progesterone can induce or inhibit the microsomal Cytochrome P450 metabolism. Plasma protein-binding of albendazole sulphoxide and albendazole sulphone has been studied between male and female sheep, also their binding to sheep albumin and globulins. Both albendazole metabolites readily bind to sheep albumin and globulins. Male animals show a significantly lower binding of albendazole metabolites than females. These differences could be responsible for the non-esterified fatty acids (NEFA) present in the plasma. Males have significantly higher plasma levels of NEFA than females and which may compete with albumin for binding to albendazole metabolites.

  1. ENANTIOMER-SPECIFIC FATE AND EFFECTS OF MODERN CHIRAL PESTICIDES

    EPA Science Inventory

    This slide presentation presents enantiomer-specific fate and effects of modern chiral pesticides. The research areas presented were analytical separation of enantiomers; environmental occurrence of enantiomers; transformation rates and enantioselectivity; bioaccumulation; and e...

  2. LC-MS/MS methods for albendazole analysis in feed and its metabolite residues in fish fillet and a leaching study in feed after an alternative procedure for drug incorporation.

    PubMed

    Busatto, Zenaís; da Silva, Agnaldo Fernando Baldo; de Freitas, Osvaldo; Paschoal, Jonas Augusto Rizzato

    2017-04-01

    This paper describes the development of analytical methods for the quantification of albendazole (ABZ) in fish feed and ABZ and its main known metabolites (albendazole sulfoxide, albendazole sulfone and albendazole aminosulfone) in fish fillet employing LC-MS/MS. In order to assess the reliability of the analytical methods, evaluation was undertaken as recommended by related guides proposed by the Brazilian Ministry of Agriculture for analytical method validation. The calibration curve for ABZ quantification in feed showed adequate linearity (r > 0.99), precision (CV < 1.03%) and trueness ranging from 99% to 101%. The method for ABZ residues in fish fillet involving the QuEChERS technique for sample extraction had adequate linearity (r > 0.99) for all analytes, precision (CV < 13%) and trueness around 100%, with CCα < 122 ng g(-)(1) and CCβ < 145 ng g(-)(1). Besides, by aiming to avoid the risk of ABZ leaching from feed into the aquatic environment during fish medication via the oral route, a promising procedure for drug incorporation in the feed involving coating feed pellets with ethyl cellulose polymer containing ABZ was also evaluated. The medicated feed had good homogeneity (CV < 3%) and a lower release of ABZ (< 0.2%) from feed to water when the medicated feed stayed in the water for up to 15 min.

  3. Photonastic effects in ruthenium sulfoxide polymers

    NASA Astrophysics Data System (ADS)

    Rack, Jeffrey J.; Livshits, Maksim Y.; Shin, Jisoo

    2016-09-01

    We have established that film morphology and laser induced heating from dye absorption are important parameters in the creation of new photonastic materials. Photonastic is defined as regular, repeatable movement in a pre-programmed direction following exposure to light. This work builds upon the development of photonastic polymers of ruthenium sulfoxide complexes, where the action of bending is ascribed to phototriggered isomerization of a sulfoxide ligand in a ruthenium coordination complex that is covalently attached to polynorbornene. The bending is analyzed in terms of a bilayer cantilever model.

  4. Metabolic profiling of praziquantel enantiomers.

    PubMed

    Wang, Haina; Fang, Zhong-Ze; Zheng, Yang; Zhou, Kun; Hu, Changyan; Krausz, Kristopher W; Sun, Dequn; Idle, Jeffrey R; Gonzalez, Frank J

    2014-07-15

    Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher the metabolic pathways and enantioselective metabolic differences of PZQ. Many phase I and four new phase II metabolites were found in urine and feces samples of mice 24h after dosing, indicating that the major metabolic reactions encompassed oxidation, dehydrogenation, and glucuronidation. Differences in the formation of all these metabolites were observed between (R)-PZQ and (S)-PZQ. In an in vitro phase I incubation system, the major involvement of CYP3A, CYP2C9, and CYP2C19 in the metabolism of PZQ, and CYP3A, CYP2C9, and CYP2C19 exhibited different catalytic activity toward the PZQ enantiomers. Apparent Km and Vmax differences were observed in the catalytic formation of three mono-oxidized metabolites by CYP2C9 and CYP3A4 further supporting the metabolic differences for PZQ enantiomers. Molecular docking showed that chirality resulted in differences in substrate location and conformation, which likely accounts for the metabolic differences. In conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel.

  5. Abdominal Cystic Echinococcosis Treated with Albendazole. A Pediatric Cohort Study

    PubMed Central

    Moroni, Samanta; Moscatelli, Guillermo; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Freilij, Héctor; Salgueiro, Fabián; Altcheh, Jaime

    2016-01-01

    Introduction Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. Objective To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. Population and Methods Patients (0–18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10–15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. Results A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. Conclusion Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention. PMID:27589236

  6. 21 CFR 524.660a - Dimethyl sulfoxide solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dimethyl sulfoxide solution. 524.660a Section 524.660a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dimethyl sulfoxide solution. (a) Specifications. Dimethyl sulfoxide contains 90 percent of...

  7. 21 CFR 524.660a - Dimethyl sulfoxide solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dimethyl sulfoxide solution. 524.660a Section 524.660a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dimethyl sulfoxide solution. (a) Specifications. Dimethyl sulfoxide contains 90 percent of...

  8. 21 CFR 524.660a - Dimethyl sulfoxide solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dimethyl sulfoxide solution. 524.660a Section 524.660a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dimethyl sulfoxide solution. (a) Specifications. Dimethyl sulfoxide contains 90 percent of...

  9. In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers against Echinococcus multilocularis Metacestodes▿

    PubMed Central

    Stadelmann, Britta; Küster, Tatiana; Scholl, Sabrina; Barna, Fabienne; Kropf, Christian; Keiser, Jennifer; Boykin, David W.; Stephens, Chad E.; Hemphill, Andrew

    2011-01-01

    The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new and more efficient treatment options are urgently needed. By employing a recently validated assay based on the release of functional phosphoglucose isomerase (PGI) from dying parasites, the activities of 26 dicationic compounds and of the (+)- and (−)-erythro-enantiomers of mefloquine were investigated. Initial screening of compounds was performed at 40 μM, and those compounds exhibiting considerable antiparasitic activities were also assessed at lower concentrations. Of the dicationic drugs, DB1127 (a diguanidino compound) with activities comparable to nitazoxanide was further studied. The activity of DB1127 was dose dependent and led to severe structural alterations, as visualized by electron microscopy. The (+)- and (−)-erythro-enantiomers of mefloquine showed similar dose-dependent effects, although higher concentrations of these compounds than of DB1127 were required for metacestode damage. In conclusion, of the drugs investigated here, the diguanidino compound DB1127 represents the most promising compound for further study in appropriate in vivo models for Echinococcus multilocularis infection. PMID:21768518

  10. ENANTIOMER-SPECIFIC EFFECTS OF CHIRAL POLLUTANTS

    EPA Science Inventory

    Enantiomers, the mirror image isomers of chiral pollutants, are known to be selective in their interaction with other chiral molecules, including enzymes and other biochemicals. Considerable research has shown, for example, that chiral pesticides are degraded selectively by micr...

  11. Cysteine sulfoxide derivatives in Petiveria alliacea.

    PubMed

    Kubec, R; Musah, R A

    2001-11-01

    Two diastereomers of S-benzyl-L-cysteine sulfoxide have been isolated from fresh roots of Petiveria alliacea. Their structures and absolute configurations have been determined by NMR, MALDI-HRMS, IR and CD spectroscopy and confirmed by comparison with authentic compounds. Both the R(S) and S(S) diastereomers of the sulfoxide are present in all parts of the plant (root, stem, and leaves) with the latter diastereomer being predominant. Their total content greatly varied in different parts of the plant between 0.07 and 2.97 mg g(-1) fr. wt, being by far the highest in the root. S-Benzylcysteine has also been detected in trace amounts (<10 microg g(-1) fr. wt) in all parts of the plant. This represents the first report of the presence of S-benzylcysteine derivatives in nature.

  12. Dimethyl sulfoxide inhibits bioactivation of sulindac.

    PubMed

    Swanson, B N; Boppana, V K; Vlasses, P H; Rotmensch, H H; Ferguson, R K

    1983-07-01

    Sulindac, a nonsteroidal anti-inflammatory agent, is converted to a bioactive sulfide metabolite via reversible reduction of its sulfoxide moiety. To test whether DMSO can inhibit conversion of sulindac to its active form, eight healthy men received, in a randomized, crossover manner, 400 mg of sulindac, orally, either alone or 60 min after an oral dose of DMSO (30 ml, 70% solution). After the drug combination, mean plasma concentrations of the sulfide metabolite were significantly lower than in controls at 1.5, 2, 3, 4, and 8 hr after sulindac administration. The mean area under the plasma sulfide concentration-time curve for 0 to 12 hr was 30% (range 7% to 56%) lower after DMSO treatment. This study suggests that DMSO can inhibit metabolism of other sulfoxides in man and may antagonize the therapeutic efficacy of sulindac.

  13. Methionine sulfoxide reductase contributes to meeting dietary methionine requirements

    PubMed Central

    Zhao, Hang; Kim, Geumsoo; Levine, Rodney L.

    2012-01-01

    Methionine sulfoxide reductases are present in all aerobic organisms. They contribute to antioxidant defenses by reducing methionine sulfoxide in proteins back to methionine. However, the actual in vivo roles of these reductases are not well defined. Since methionine is an essential amino acid in mammals, we hypothesized that methionine sulfoxide reductases may provide a portion of the dietary methionine requirement by recycling methionine sulfoxide. We used a classical bioassay, the growth of weanling mice fed diets varying in methionine, and applied it to mice genetically engineered to alter the levels of methionine sulfoxide reductase A or B1. Mice of all genotypes were growth retarded when raised on chow containing 0.10% methionine instead of the standard 0.45% methionine. Retardation was significantly greater in knockout mice lacking both reductases. We conclude that the methionine sulfoxide reductases can provide methionine for growth in mice with limited intake of methionine, such as may occur in the wild. PMID:22521563

  14. Absorption of nitrogen oxides by sulfoxides and sulfones

    SciTech Connect

    Bikbaeva, G.G.; Isyangil'dina, A.Kh.; Baranovskaya, E.M.; Nikitin, Yu.E.

    1986-10-10

    Petroleum sulfoxides (PSO) have high sorption capacity for NO/sub 2/. In view of their comparative availability and low cost, PSO may be of practical interest as absorbents for nitrogen oxides. At the same time, the properties of adducts formed by sulfoxides, both individual and from petroleum, with nitrogen oxides have been studies very little. In this work the methods of IR and UV spectroscopy were used for studying complex formation of nitrogen oxides with sulfoxides, and also with sulfones, obtained by oxidation of sulfoxides.

  15. Enantiomer Ratios of Meteoritic Sugar Derivatives

    NASA Technical Reports Server (NTRS)

    Cooper, George

    2012-01-01

    Carbonaceous meteorites contain a diverse suite of soluble organic compounds. Studies of these compounds reveal the Solar System's earliest organic chemistry. Among the classes of organic compounds found in meteorites are keto acids (pyruvic acid, etc.), hydroxy tricarboxylic acids (1), amino acids, amides, purines and pyrimidines. The Murchison and Murray meteorites are the most studied for soluble and insoluble organic compounds and organic carbon phases. The majority of (indigenous) meteoritic compounds are racemic, (i.e., their D/L enantiomer ratios are 50:50). However, some of the more unusual (non-protein) amino acids contain slightly more of one enantiomer (usually the L) than the other. This presentation focuses on the enantiomer analyses of three to six-carbon (3C to 6C) meteoritic sugar acids. The molecular and enantiomer analysis of corresponding sugar alcohols will also be discussed. Detailed analytical procedures for sugar-acid enantiomers have been described. Results of several meteorite analyses show that glyceric acid is consistently racemic (or nearly so) as expected of non-biological mechanisms of synthesis. Also racemic are 4-C deoxy sugar acids: 2-methyl glyceric acid; 2,4-dihydroxybutyric acid; 2,3-dihydroxybutyric acid (two diastereomers); and 3,4-dihydroxybutyric acid. However, a 4C acid, threonic acid, has never been observed as racemic, i.e., it possesses a large D excess. In several samples of Murchison and one of GRA 95229 (possibly the most pristine carbonaceous meteorite yet analyzed) threonic acid has nearly the same D enrichment. In Murchison, preliminary isotopic measurements of individual threonic acid enantiomers point towards extraterrestrial sources of the D enrichment. Enantiomer analyses of the 5C mono-sugar acids, ribonic, arabinonic, xylonic, and lyxonic also show large D excesses. It is worth noting that all four of these acids (all of the possible straight-chained 5C sugar acids) are present in meteorites, including the

  16. [Membrane potential before and after deep freezing of Escherichia coli in the presence of dimethyl sulfoxide and diethyl sulfoxide].

    PubMed

    Markarian, Sh A; Bagramian, K A; Arakelian, V B

    2002-01-01

    It was shown by the method of penetrating tetraphenylphosphonium cations that low-temperature freezing (-196 degrees C) of Escherichia coli leads to a sharp decrease (from 198 to 85 mV) in membrane potential. Incubation of bacteria in a medium containing dimethyl sulfoxide and diethyl sulfoxide as cryoprotectors results in a reduction of the potential by 16 and 27 mV, respectively. It was also shown that diethyl sulfoxide is more effective in maintaining the membrane potential after freezing--thawing than dimethyl sulfoxide.

  17. Enantiomers of a nonylphenol isomer: absolute configurations and estrogenic potencies.

    PubMed

    Zhang, Haifeng; Oppel, Iris M; Spiteller, Michael; Guenther, Klaus; Boehmler, Gabriele; Zuehlke, Sebastian

    2009-02-01

    Enantiomers of 4-(1,1,2-trimethylhexyl)phenol, a chiral isomer of the endocrine disrupting chemical nonylphenol, have been resolved and isolated by preparative chiral HPLC. The absolute configurations of the enantiomers were then determined by an X-ray crystallographic study of the (-)-camphanoyl derivative of the first eluted enantiomer NP(35)E1. The first enantiomer (NP(35)E1) and the second enantiomer (NP(35)E2) eluted were found to have the S and R absolute configurations, respectively. The estrogenic potencies of the S and R enantiomers were tested by the E-screen assay. A slight difference was observed in the relative proliferative effect between the S enantiomer and R enantiomer in the E-screen assay.

  18. Two new bicyclic sulfoxides from Welsh onion.

    PubMed

    Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kotaro; Ono, Masateru; El-Aasr, Mona; Nakano, Daisuke; Kinjo, Junei

    2016-04-01

    Newly identified bicyclic sulfoxides, welsonins A1 (1) and A2 (2), were isolated from acetone extracts of the bulbs of the Welsh onion (Allium fistulosum). In this study, the structures of 1 and 2, which are tetrahydrothiophene-S-oxide derivatives, were characterized by spectroscopic analysis. These compounds appeared to be derived from the coupling of 1-propenyl sulfenic acid and uronic acid. Welsonin A1 (1) showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of alternatively activated M2 macrophages.

  19. General route to racemic and enantiomeric carbo- and heterocyclic vinyl sulfoxides via tandem Michael addition/Horner olefination of alpha-phosphorylvinyl sulfoxides.

    PubMed

    Mikołajczyk, Marian; Krysiak, Jerzy A; Midura, Wanda H; Wieczorek, Michał W; Rózycka-Sokołowska, Ewa

    2006-11-10

    A new one-pot synthesis of heterocyclic and carbocyclic vinyl sulfoxides has been developed which involves reaction of alpha-phosphorylvinyl sulfoxides with carbonyl compounds bearing oxygen, nitrogen, and carbon nucleophilic centers. Use of optically active alpha-phosphorylvinyl p-tolyl sulfoxides in this tandem Michael addition/Horner olefination reaction leads to the corresponding optically active cyclic sulfoxides. In this way, a variety of optically active chromene, pyrrolizine, chinoline, and cyclopentene sulfoxides have been efficiently prepared.

  20. Enantioselective liver microsomal sulphoxidation of albendazole in cattle: effect of nutritional status.

    PubMed

    Virkel, G; Lifschitz, A; Soraci, A; Sansinanea, A; Lanusse, C

    2000-04-01

    1. The enantioselective liver microsomal sulphoxidation of the benzimidazole anthelmintic, albendazole (ABZ), by cattle liver microsomes has been investigated. The influence of nutritional condition on this biotransformation process was also characterized. 2. ABZ was oxidized to its sulphoxide metabolite (ABZSO) in a NADPH concentration-dependent reaction and the (+) and (-) ABZSO enantiomers formed were identified. 3. Vmax (0.27 nmol ABZSO formed per min x mg(-1) microsomal protein) and Km (15.10 microM) for ABZ sulphoxidation by cattle liver microsomes were obtained. Different Vmax (0.11 and 0.16 nmol x min(-1) x mg(-1)) and Km (9.40 and 26.70 microM) characterized the enantioselective formation of (+) and (-) ABZSO antipodes, respectively. 4. Free fatty acid (FFA) concentrations and beta-hydroxybutyrate concentrations (beta-OHB) in serum and liver homogenates were significantly higher in feed-restricted (poor nutritional condition) compared with control animals in an optimal nutritional status. Serum protein concentrations and liver cytosolic glucose 6-phosphate dehydrogenase (G6PD) activity were significantly lower in the feed-restricted compared with control calf. 5. Animal nutritional condition affected the pattern of ABZ sulphoxidation. A higher Km for (total) ABZSO and (+) ABZSO production was observed in the calf subjected to a period of undernutrition. 6. A nutritionally induced impairment in the affinity of microsomal mixed-function oxidases responsible of ABZ oxidation may be responsible for the observed changes in the liver microsomal sulphoxidation of ABZ in the feed-restricted calf. Furthermore, undernutrition may affect primarily the FMO-mediated formation of (+) ABZSO. These in vitro observations agree with the changes observed in vivo following the administration of ABZ to the calf subjected to a dietary restriction.

  1. Determination of lansoprazole enantiomers in dog plasma by column-switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.

    PubMed

    Wang, Hao; Sun, Yantong; Meng, Xiangjun; Yang, Bo; Wang, Jian; Yang, Yan; Gu, Jingkai

    2015-09-01

    Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion.

  2. Albendazole-induced liver injury: a case report

    PubMed Central

    Restrepo, Juan C

    2013-01-01

    We report a case of a 47-year-old male, who was referred to the clinical hepatology services at Pablo Tobón Uribe Hospital for evaluation of a jaundice syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and the patient was treated with albendazole; however, after five months of uninterrupted treatment the patient again consulted and his liver test showed marked hepatocellular damage. This time, the patient was diagnosed with drug-induced liver injury due to albendazole, based on information from the clinical record, history of drug consumption, clinical and laboratory tests improved after discontinuing the medication and after discarding other possible causes; this diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely" correlation between hepatocellular damage and drug toxicity etiology. PMID:24892458

  3. [EXPERIENCE IN TREATING HELMINTHISM WITH MICRONIZED ALBENDAZOLE (GELMODOL)].

    PubMed

    Zavoikin, V D; Tumolskaya, N I; Mazmanyan, M V; Zelya, O P; Tikhonova, D V

    2015-01-01

    The paper gives the results of treatment with micronized albendazole (Gelmodol-BM, World Medicine, UK) in 87 patients of the Department of Medical Parasitology and Tropical Diseases, Clinical and Diagnostic Center, Clinical Center, I.M.Sechenov First Moscow State Medical University. Thirty-two patients with echinococcosis 8 with alveococcosis (including 4 inoperable patients), 10 with ascariasis, 10 with toxocariasis, 15 with enterobiasis, and 12 people diagnosed with larva migrans were treated in 2013-2014. The drug's routine doses and dosage regimens were used. Albendazole (Gelmodol, World Medicine, UK) showed a high efficacy with good tolerability, which is highly competitive with that of the drugs manufactured by IPCA Laboratories Ltd., India (such as nemozole). Both medicaments above-mentioned may be successfully used in the treatment of many helminthisms.

  4. Albendazole-induced liver injury: a case report.

    PubMed

    Ríos, David; Restrepo, Juan C

    2013-04-01

    We report a case of a 47-year-old male, who was referred to the clinical hepatology services at Pablo Tobón Uribe Hospital for evaluation of a jaundice syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and the patient was treated with albendazole; however, after five months of uninterrupted treatment the patient again consulted and his liver test showed marked hepatocellular damage. This time, the patient was diagnosed with drug-induced liver injury due to albendazole, based on information from the clinical record, history of drug consumption, clinical and laboratory tests improved after discontinuing the medication and after discarding other possible causes; this diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely" correlation between hepatocellular damage and drug toxicity etiology.

  5. Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology.

    PubMed

    Capriotti, Kara; Capriotti, Joseph A

    2012-09-01

    Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology.

  6. Treatment of crusted scabies with albendazole: A case report.

    PubMed

    Douri, Thaer; Shawaf, A Z

    2009-10-15

    Crusted scabies is a severe variant of scabies caused by the ectoparasite Sarcoptes scabiei. It is characterized by high mite burden, extensive hyperkeratotic scaling, crusted lesions, variable pruritus, generalized lymphadenopathy, erythroderma, and eosinophilia, in some cases. There is an increased incidence of crusted scabies, particularly among patients with HIV infection. We describe a 22-year-old Syrian immunocompetent female who had hyperkeratotic psoriasiform plaques and hyperkeratosis without itching. She was treated with oral albendazole and topical crotamiton with salicylic acid 5 percent.

  7. Albendazole-induced granulomatous hepatitis: a case report

    PubMed Central

    2013-01-01

    Introduction Drug-related hepatotoxicity is a common medical problem with implications for health systems. It constitutes a cause of acute liver failure and, in many cases, is responsible for the rejection of new pharmacological agents during efficacy and safety studies. Risk factors, as well as pathogenesis of drug-induced liver injury, are poorly understood. The diagnosis of drug-induced liver injury is challenging; it is difficult to define the cause of drug hepatotoxicity due to the heterogeneity of the clinical presentation and the absence of established criteria for accurate and reproducible identification of drug-associated liver toxicity. Case presentation We report the case of a 25-year-old Hispanic woman admitted to our Clinical Hepatology Unit with symptoms of acute hepatitis of unknown etiology. She was diagnosed with albendazole-induced granulomatous hepatitis after ruling out other possible causes, based on laboratory studies, liver biopsy, medical history, detailed drug history, and spontaneous improvement of her liver biochemical profile after medication withdrawal. This diagnosis was supported by the Council for International Organizations of Medical Sciences-Roussel Uclaf Causality Assessment Method, which showed a likely correlation between hepatocellular damage and drug toxicity as the etiology. Conclusions Our patient’s suspected diagnosis was albendazole-induced granulomatous hepatitis with confirmatory histologic pattern. This case deserves particular attention due to the wide use of albendazole in our country (Colombia) and the prevalent medical issue of drug-related hepatotoxicity. PMID:23889970

  8. Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.

    PubMed

    Seeman, P; Westman, K; Protiva, M; Jílek, J; Jain, P C; Saxena, A K; Anand, N; Humber, L; Philipp, A

    1979-06-15

    In order to identify a pair of neuroleptic enantiomers with the highest stereoselective interaction with neuroleptic/dopamine receptors, the effects of eight pairs of neuroleptic enantiomers were tested on the specific binding of 3H-spiperone to crude homogenates of calf caudate nucleus. The ratios of the Ki values were: (+)-butaclamol/(-)-butaclamol = 3000; dexclamol/(-)-analogue = 151; (+)-isobutaclamol/(-)-isobutaclamol = 146; (-)-CTC/(+)-CTC= 109; (-)-centbutindole/(+)-centbutindole = 20; S(+)-octoclothepin/R(-)-octoclothepin = 11. Thus, the neuroleptic receptor is highly stereoselective for the rigid butaclamol derivatives, but much less so for the flexible neuroleptics. The 3H-apomorphine binding site, however, had a stereoselectivity ratio of only 7 for isobutaclamol, further suggesting that the high affinity sites (i.e. nM) for 3H-neuroleptic binding and for 3H-apomorphine binding are different.

  9. Development of chiral sulfoxide ligands for asymmetric catalysis.

    PubMed

    Trost, Barry M; Rao, Meera

    2015-04-20

    Nitrogen-, phosphorus-, and oxygen-based ligands with chiral backbones have been the historic workhorses of asymmetric transition-metal-catalyzed reactions. On the contrary, sulfoxides containing chirality at the sulfur atom have mainly been used as chiral auxiliaries for diastereoselective reactions. Despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination, these compounds have only recently emerged as a versatile class of chiral ligands. In this Review, we detail the history of the development of chiral sulfoxide ligands for asymmetric catalysis. We also provide brief descriptions of metal-sulfoxide bonding and strategies for the synthesis of enantiopure sulfoxides. Finally, insights into the future development of this underutilized ligand class are discussed.

  10. The use of albendazole for the treatment of trematodiasis in two tree shrews (Tupala glis)

    USGS Publications Warehouse

    Beehler, B.A.; Tuggle, B.N.

    1983-01-01

    Albendazole is a broad-spectrum anthelmintic of the benzimidazole group which has been tested in several rodents and domestic animals. Albendazole has been used effectively to treat trematodes in sheep, cattle, dogs, and cats. The use of this anthelmintic in exotic small mammals has not been reported to the authors' knowledge.

  11. Dimethyl sulfoxide inhibits NLRP3 inflammasome activation.

    PubMed

    Ahn, Huijeong; Kim, Jeeyoung; Jeung, Eui-Bae; Lee, Geun-Shik

    2014-04-01

    Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is commonly/widely used as a solvent for biological compounds. In addition, DMSO has been studied as a medication for the treatment of inflammation, cystitis, and arthritis. Based on the anti-inflammatory characteristics of DMSO, we elucidated the effects of DMSO on activation of inflammasomes, which are cytoplasmic multi-protein complexes that mediate the maturation of interleukin (IL)-1β by activating caspase-1 (Casp1). In the present study, we prove that DMSO attenuated IL-1β maturation, Casp1 activity, and ASC pyroptosome formation via NLRP3 inflammasome activators. Further, NLRC4 and AIM2 inflammasome activity were not affected, suggesting that DMSO is a selective inhibitor of the NLRP3 inflammasomes. The anti-inflammatory effect of DMSO was further confirmed in animal, LPS-endotoxin sepsis and inflammatory bowel disease models. In addition, DMSO inhibited LPS-mediating IL-1s transcription. Taken together, DMSO shows anti-inflammatory characteristics, attenuates NLRP3 inflammasome activation, and mediates inhibition of IL-1s transcription.

  12. Thermal Sensitivity and Dimethyl Sulfoxide (DMSO).

    PubMed

    Takeda, Kotaro; Pokorski, Mieczyslaw; Okada, Yasumasa

    2016-01-01

    Dimethyl sulfoxide (DMSO) is commonly used as a solvent for hydrophobic substances, but the compound's innate bioactivity is an area of limited understanding. In this investigation we seek to determine the analgesic potential of DMSO. We addressed the issue by assessing the perception of thermal pain stimulus, using a 55 °C hotplate design, in conscious mice. The latency of withdrawal behaviors over a range of incremental accumulative intraperitoneal DMSO doses (0.5-15.5 g/kg) in the same mouse was taken as a measure of thermal endurance. The findings were that the latency, on average, amounted to 15-30 s and it differed inappreciably between the sequential DMSO conditions. Nor was it different from the pre-DMSO control conditions. Thus, DMSO did not influence the cutaneous thermal pain perception. The findings do not lend support to those literature reports that point to the plausible antinociceptive potential of DMSO as one of a plethora of its innate bioactivities. However, the findings concern the mouse's footpad nociceptors which have specific morphology and stimulus transduction pathways, which cannot exclude DMSO's antinociceptive influence on other types of pain or in other types of skin. Complex and as yet unresolved neural mechanisms of perception of cutaneous noxious heat stimulus should be further explored with alternative experimental designs.

  13. Modulation of dipalmitoylphosphatidylcholine monolayers by dimethyl sulfoxide.

    PubMed

    Dabkowska, Aleksandra P; Collins, Louise E; Barlow, David J; Barker, Robert; McLain, Sylvia E; Lawrence, M Jayne; Lorenz, Christian D

    2014-07-29

    The action of the penetration-enhancing agent, dimethyl sulfoxide (DMSO), on phospholipid monolayers was investigated at the air-water interface using a combination of experimental techniques and molecular dynamics simulations. Brewster angle microscopy revealed that DPPC monolayers remained laterally homogeneous at subphase concentrations up to a mole fraction of 0.1 DMSO. Neutron reflectometry of the monolayers in combination with isotopic substitution enabled the determination of solvent profiles as a function of distance perpendicular to the interface for the different DMSO subphase concentrations. These experimental results were compared to those obtained from molecular dynamic (MD) simulations of the corresponding monolayer systems. There was excellent agreement found between the MD-derived reflectivity curves and the measured data for all of the H/D contrast variations investigated. The MD provide a detailed description of the distribution of water and DMSO molecules around the phosphatidylcholine headgroup, and how this distribution changes with increasing DMSO concentrations. Significantly, the measurements and simulations that are reported here support the hypothesis that DMSO acts by dehydrating the phosphatidylcholine headgroup, and as such provide the first direct evidence that it does so primarily by displacing water molecules bound to the choline group.

  14. Toward novel antiparasitic formulations: Complexes of Albendazole desmotropes and β-cyclodextrin.

    PubMed

    Chattah, Ana K; Pfund, Laura Y; Zoppi, Ariana; Longhi, Marcela R; Garnero, Claudia

    2017-05-15

    Novel complexes of two different solid forms of Albendazol and β-cyclodextrin were investigated in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. The interaction between each form of Albendazol and β-cyclodextrin was studied in solution and solid state, in order to investigate their effect on the solubility and dissolution rate of Albendazol solid forms. The solid supramolecular systems were characterized using a variety of techniques including natural-abundance (13)C cross-polarization magic-angle-spinning nuclear magnetic resonance, powder X-ray diffraction, Fourier transform-infrared spectroscopy and scanning electron microscopy. The results obtained showed the highest increment of solubility and dissolution rate, in simulated gastric fluid, for the Albendazole II:β-cyclodextrin systems. Thus, these new complexes constitute an interesting alternative for improving the oral bioavailability of Albendazol.

  15. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

    PubMed Central

    Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

    2016-01-01

    Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole

  16. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-07

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

  17. Glass transition dynamics of enantiomer (+)-ibuprofen

    NASA Astrophysics Data System (ADS)

    Kim, Tae Hyun; Ko, Jae-Hyeon; Takayama, Haruki; Shibata, Tomohiko; Kojima, Seiji

    2013-02-01

    The acoustic properties and dynamic heat capacity of enantiomer (+)-Ibuprofen were investigated in a wide temperature including glassy and supercooled liquid and equilibrium liquid states. The Brillouin frequency shift and the full width at half maximum of the longitudinal acoustic waves of glassy ibuprofen exhibited clear changes at the glass transition temperature of 223 K. The fragility of (+)-Ibuprofen was determined to be 68 using the temperature dependence of relaxation time obtained from the imaginary part of the complex dynamic heat capacity. The sound velocity, the attenuation coefficient, and the thermal expansion coefficient were determined in the liquid (+)-Ibuprofen based on the measurements of the refractive index.

  18. A Novel Method for Assigning R, S Labels to Enantiomers.

    ERIC Educational Resources Information Center

    Huheey, James E.

    1986-01-01

    Discusses ways of teaching students about how to assign R (rectus) and S (sinister) labels to enantiomers by using their hands as models. The chirality of the human hands follows the Cahn-Ingold-Prelog Rules for assigning enantiomers and infers the correct chirality of molecules shown in two-dimensional drawings. (TW)

  19. Toxicity of Triadimefon Racemate and Enantiomers to Black Fly Larvae

    EPA Science Inventory

    Triadimefon is a conazole fungicide commonly used for commercial and agricultural fungal control on trees, ornamentals and fruits. It is a chiral compound, existing as R-(-) and S-(+) enantiomers and used as the racemate. This is of interest since the triadimefon enantiomers ca...

  20. Voltammetric discrimination of mandelic acid enantiomers.

    PubMed

    Zor, Erhan; Saf, Ahmet O; Bingol, Haluk; Ersoz, Mustafa

    2014-03-15

    We report a novel electrochemical biosensor for direct discrimination of D- and L-mandelic acid (D- and L-MA) in aqueous medium. The glassy carbon electrode (GCE) surface was modified with reduced graphene oxide (rGO) and γ-globulin (GLOB). Electrochemical characterization of the modified electrodes was investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The modified electrode surfaces were also characterized by scanning electron microscopy. Electrochemical response of the prepared electrode (GCE/rGO/GLOB) for discrimination of D- and L-MA enantiomers was investigated by cyclic voltammetry and was compared with bare GCE in the concentration range of 2 to 10 mM. Whereas the bare GCE showed no electrochemical response for the MA enantiomers, the GCE/rGO/GLOB electrode exhibited direct and selective discrimination with different oxidation potential values of 1.47 and 1.71 V and weak reduction peaks at potential values of -1.37 and -1.48 V, respectively. In addition, electrochemical performance of the modified electrode was investigated in mixed solution of D- and L-MA. The results show that the produced electrode can be used as electrochemical chiral biosensor for MA.

  1. Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

    PubMed Central

    Ryan, Michael C; Rao, Meera

    2016-01-01

    Summary A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent. PMID:27559366

  2. Polymer-based monolithic column with incorporated chiral metal-organic framework for enantioseparation of methyl phenyl sulfoxide using nano-liquid chromatography.

    PubMed

    Wang, Xin; Lamprou, Alexandros; Svec, Frantisek; Bai, Yu; Liu, Huwei

    2016-12-01

    A new approach to the preparation of enantioselective porous polymer monolithic columns with incorporated chiral metal-organic framework for nano-liquid chromatography has been developed. While no enantioseparation was achieved with monolithic poly(4-vinylpyridine-co-ethylene dimethacrylate) column, excellent separations of both enantiomers of (±)-methyl phenyl sulfoxide were achieved with its counterpart prepared after admixing metal-organic framework [Zn2 (benzene dicarboxylate)(l-lactic acid)(dmf)], which is synthesized from zinc nitrate, l-lactic acid, and benzene dicarboxylic acid in the polymerization mixture. These novel monolithic columns combined selectivity of the chiral framework with the excellent hydrodynamic properties of polymer monoliths, may provide a great impact on future studies in the field of chiral analysis by liquid chromatography.

  3. 21 CFR 524.981e - Fluocinolone and dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Fluocinolone and dimethyl sulfoxide otic solution... ANIMAL DRUGS § 524.981e Fluocinolone and dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 60 percent dimethyl sulfoxide....

  4. 21 CFR 524.981d - Fluocinolone and dimethyl sulfoxide solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Fluocinolone and dimethyl sulfoxide solution. 524... ANIMAL DRUGS § 524.981d Fluocinolone and dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent dimethyl sulfoxide....

  5. Albendazole kinetics in patients with echinococcosis: delayed absorption and impaired elimination in cholestasis.

    PubMed

    Cotting, J; Zeugin, T; Steiger, U; Reichen, J

    1990-01-01

    The pharmacokinetics of albendazole and its main metabolite, albendazole sulphoxide, have been examined after giving a single oral dose of 200 mg albendazole to 19 patients with either Echinococcus multilocularis or E. granulosus, 5 of whom had significant extrahepatic obstruction due to the underlying disease. The AUC of albendazole sulphoxide was increased in the latter patients (mean 122 mumols.h.l-1 compared to 17 mumols.h.l-1 in the non-obstructed group). Obstructed patients had delayed absorption, ka averaging 0.39 compared to 1.41 h-1 in non-obstructed patients. The corresponding elimination rate constant, ke was also prolonged, averaging 0.041 and 0.13 h-1 in the two groups, respectively. Four patients were restudied after complete or partial resolution of the cholestasis. The pharmacokinetic parameters in them had returned towards values comparable to those in the non-obstructed patients.

  6. [Albendazole in Japanese juvenile with enterobiasis in whom pyrantel pamoate is not effective].

    PubMed

    Ohnishi, Kenji; Kobayashi, Ken-ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi

    2011-09-01

    A 18-year-old Japanese woman seen as an outpatient for refractory enterobiasis had been treated with pyrantel pamoate over 40 times since the age of 11. She washed her hands and cleaned house frequently, and all family members took pyrantel pamoate, but Enterobius vermicularis eggs remained. She was orally administered 400 mg of albendazole 3 times in clinic visits, after which eggs have not been seen for 1 year. Pyrantel pamoate is used widely against enterobiasis in Japan. Our case shows albendazole to also be effective against enterobiasis. Albendazole thus appears to be a useful anti-helminthic in enterobiasis patients in whom pyrantel pamoate is not effective. This is, to our knowledge, the first case of enterobiasis treated with albendazole in Japan.

  7. Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos.

    PubMed

    Carlsson, Gunnar; Patring, Johan; Ullerås, Erik; Oskarsson, Agneta

    2011-07-01

    Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3μM. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity.

  8. A case of ocular toxocariasis successfully treated with albendazole and triamcinolon.

    PubMed

    Seong, San; Moon, Daruchi; Lee, Dong Kyu; Kim, Hyung Eun; Oh, Hyun Sup; Kim, Soon Hyun; Kwon, Oh Woong; You, Yong Sung

    2014-10-01

    We present a case of ocular toxocariasis treated successfully with oral albendazole in combination with steroids. A 26-year-old male visited the authors' clinic with the chief complaint of flying flies in his right eye. The fundus photograph showed a whitish epiretinal scar, and the fluorescein angiography revealed a hypofluorescein lesion of the scar and late leakage at the margin. An elevated retinal surface and posterior acoustic shadowing of the scar were observed in the optical coherence tomography, and Toxocara IgG was positive. The patient was diagnosed with toxocariasis, and the condition was treated with albendazole (400 mg twice a day) for a month and oral triamcinolone (16 mg for 2 weeks, once a day, and then 8 mg for 1 week, once a day) from day 13 of the albendazole treatment. The lesions decreased after the treatment. Based on this study, oral albendazole combined with steroids can be a simple and effective regimen for treating ocular toxocariasis.

  9. The cytotoxicity study of praziquantel enantiomers.

    PubMed

    Sun, Qian; Mao, Ruifeng; Wang, Dongling; Hu, Changyan; Zheng, Yang; Sun, Dequn

    2016-01-01

    Praziquantel (PZQ) is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ), which is composed of (R)-PZQ and (S)-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R)-PZQ and (S)-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay. Results revealed that (R)-PZQ had negligible cytotoxicity against L-02, SH-SY5Y, HUVEC, A549, HCT-15, and Raw264.7 cells but selectively inhibited tumor cell lines (prf-plc-5 and HepG2). However, in contrast to (R)-PZQ, the (S)-isomer showed higher cytotoxicity against L-02 cells and lower inhibition on prf-plc-5 and HepG2 cells. Besides, (R)-PZQ showed lower cytotoxicity on SH-SY5Y cells than (S)-PZQ. Meanwhile, (R)-PZQ at <80 μM concentration could promote proliferation of macrophage cells (Raw264.7). Our research revealed that (R)-PZQ has lower cytotoxicity than (S)-PZQ and has similar cytotoxicity with rac-PZQ. (S)-PZQ is the principal enantiomer to cause side effects on human definitive hosts. These findings gave the reasonable reasons for World Health Organization to produce (R)-PZQ as a replacement for rac-PZQ for the treatment of schistosomiasis.

  10. Effect of dimethyl sulfoxide on sulindac disposition in rats.

    PubMed

    Swanson, B N; Mojaverian, P; Boppana, V K; Dudash, M R

    1981-01-01

    Sulindac and dimethyl sulfoxide (DMSO) are both effective antiinflammatory agents in man. Since the sulfoxide moiety in these compounds is metabolized similarly, a biochemical interaction between the two drugs in vivo was thought to be possible. After iv injections of sulindac (5 mg/kg), plasma concentrations of sulindac, and its sulfide and sulfone metabolites, were measured in normal rats and in rats that had received, 30 min earlier, a single ip dose of DMSO (0.1, 0.5, or 1.0 ml). The half-life of sulindac (normally 94 min) was increased significantly by DMSO (0.1, 0.5, or 1.0 ml). The half-life of sulindac (normally 94 min) was increased significantly by DMSO (408 min after 1.0 ml of DMSO). Plasma sulfide metabolite levels were reduced in a dose-related manner by DMSO (93% reduction in peak concentration after 1.0 ml of DMSO). Sulfone metabolite concentration was also significantly diminished by the highest dose of DMSO. Similarly, DMSO was shown to decrease conversion of sulindac to sulfide and sulfone metabolites by rat liver enzymes in vitro. Sulfoxide reductase was more sensitive to DMSO inhibition than was sulfoxide oxidase both in vivo and in vitro. These data demonstrate that DMSO can significantly alter in vivo the formation of the pharmacologically active, sulfide metabolite of sulindac; therefore, concurrent use of DMSO and sulindac should be approached with caution.

  11. Efficacy of intraruminal albendazole boluses against Dicrocoelium dendriticum in sheep.

    PubMed

    Corba, J; Krupicer, I

    1992-01-01

    The anthelmintic potential of albendazole (ABZ) in intraruminal boluses (Proftril-Captec) was investigated in sheep harbouring naturally acquired Dicrocoelium infection. The anthelmintic efficacy was assessed by coprological testing during the autumn pasture and comparison of worm counts in 22 necropsied animals (11 treated and 11 untreated) at the end of the experiment. The mean faecal egg count (EPG) in treated animals dropped significantly during week 2, and between the 4th and the 12th week the faecal samples were almost negative. The health status of treated animals improved significantly during the first 2 weeks. Helminthological dissection of livers and small intestines revealed 91.8% efficacy, but a small number of live adult flukes were found in all treated animals.

  12. Demonstration of Enantiomer Specificity of Proteins and Drugs

    ERIC Educational Resources Information Center

    Anderson, Gretchen L.; Page, Shallee T.

    2004-01-01

    Classroom demonstrations and activities are used to illustrate the properties of enantiomer. During this activity, in a relatively short time students develop a working knowledge of the importance of stereochemistry in biochemistry and its effect on drug design and metabolism.

  13. Methionine Sulfoxide Reductases Are Essential for Virulence of Salmonella Typhimurium

    PubMed Central

    Rouf, Syed Fazle; Kitowski, Vera; Böhm, Oliver M.; Rhen, Mikael; Jäger, Timo; Bange, Franz-Christoph

    2011-01-01

    Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H2O2, and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H2O2, as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium. PMID:22073230

  14. Monitoring ibuprofen enantiomers released from polymeric systems.

    PubMed

    Simó, C; Gallardo, A; Parejo, C; San Román, J; Barbas, C; Cifuentes, A

    2002-07-01

    Two methacrylic derivatives of ibuprofen (N-[4-[2-(4-isobutylphenyl)propionyloxy]phenyl] methacrylamide (MAI) and 2-[(4-isobutylphenyl)propionyloxy]ethyl methacrylate (MEI)) were used together with 2-hydroxyethyl methacrylate (HEMA) to synthesize four polymeric materials: two hydrophobic homopolymers, PMAI and PMEI, and two hydrophilic copolymers containing 70% (w/w) HEMA, MAI-HEMA 30 and MEI-HEMA 30. The enantiomeric determination of R- and S-IBU released from these four systems has been carried out by capillary electrophoresis. Release of R- and S-IBU was monitored during in vitro assays done at 37 degrees C at pH 7.4 and 10 in buffered solutions and rat plasma. There is a hydrolytical activation in plasma and at pH 10 compared to pH 7.4; moreover, the release rate from the copolymers is much higher than from the homopolymers as a consequence of the greater hydrophilic character. A slight excess of the S-enantiomer of IBU is observed in all the experiments, being more relevant at higher release rates, i.e. copolymers at pH 10.

  15. Chromatographic Separation of Vitamin E Enantiomers.

    PubMed

    Fu, Ju-Yen; Htar, Thet-Thet; De Silva, Leanne; Tan, Doryn Meam-Yee; Chuah, Lay-Hong

    2017-02-04

    Vitamin E is recognized as an essential vitamin since its discovery in 1922. Most vegetable oils contain a mixture of tocopherols and tocotrienols in the vitamin E composition. Structurally, tocopherols and tocotrienols share a similar chromanol ring and a side chain at the C-2 position. Owing to the three chiral centers in tocopherols, they can appear as eight different stereoisomers. Plant sources of tocopherol are naturally occurring in the form of RRR while synthetic tocopherols are usually in the form of all-racemic mixture. Similarly, with only one chiral center, natural tocotrienols occur as the R-isoform. In this review, we aim to discuss a few chromatographic methods that had been used to separate the stereoisomers of tocopherols and tocotrienols. These methods include high performance liquid chromatography, gas chromatography and combination of both. The review will focus on method development including selection of chiral columns, detection method and choice of elution solvent in the context of separation efficiency, resolution and chiral purity. The applications for separation of enantiomers in vitamin E will also be discussed especially in terms of the distinctive biological potency among the stereoisoforms.

  16. Enantiomer-specific selection of amino acids

    PubMed Central

    Ren, Xueying; Tellez, Luis A; de Araujo, Ivan E

    2013-01-01

    Dietary intake of L-amino acids impacts on several physiological functions, including the control of gastrointestinal motility, pancreatic secretion, and appetite. However, the biological mechanisms regulating behavioral predilections for certain amino acid types remain poorly understood. We tested the hypothesis that, in mice, the potency with which a given glucogenic amino acid increases glucose utilization reflects its rewarding properties. We have found that: 1. During long-, but not short-, term preference tests, L-alanine and L-serine were preferred over their D-enantiomer counterparts, while no such effect was observed for L-threonine vs. D-threonine; 2. These behavioral patterns were closely associated with the ability of L-amino acids to promote increases in respiratory exchange ratios such that those, and only those, L-amino acids able to promote increases in respiratory exchange ratios were preferred over their D-isomers; 3. These behavioral preferences were independent of gustatory influences, since taste-deficient Trpm5 knockout mice displayed ingestive responses very similar to those of their wild-type counterparts. We conclude that the ability to promote increases in respiratory exchange ratios enhances the reward value of nutritionally relevant amino acids, and suggest a mechanistic link between substrate utilization and amino acid preferences. PMID:24072505

  17. Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity

    PubMed Central

    Zhang, Qingzhou; Jiang, Fan; Zhao, Bingchuan; Lin, Huacan; Tian, Yuan; Xie, Mingsheng; Bai, Guoyun; Gilbert, Adam M.; Goetz, Gilles H.; Liras, Spiros; Mathiowetz, Alan A.; Price, David A.; Song, Kun; Tu, Meihua; Wu, Yujie; Wang, Tao; Flanagan, Mark E.; Wu, Yun-Dong; Li, Zigang

    2016-01-01

    Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity. PMID:27934919

  18. Inhibition of sulindac metabolism by dimethyl sulfoxide in the rat.

    PubMed

    Swanson, B N; Mojaverian, P; Boppana, V K

    1983-01-01

    Dimethyl sulfoxide (DMSO) suppresses conversion of the prodrug sulindac to its bioactive sulfide metabolite (SD) by competitively inhibiting sulfoxide reductase. During continuous iv infusions of sulindac (1 mg/kg X h), plasma concentrations of SD at steady-state equilibrium were 80% lower when DMSO was infused concomitantly at 0.34 ml/kg X h, whereas sulindac plasma concentrations were not significantly affected by DMSO. Dermal application and intragastric administration of DMSO also inhibited SD accumulation in plasma. DMSO was only a weak inhibitor of SD oxidation in vitro and did not affect the rate of SD elimination in vivo. In contrast, dimethyl sulfide, a metabolite of DMSO, was a potent inhibitor of SD oxidase in vitro. These data suggest that DMSO can inhibit bioactivation and, hence, the antiinflammatory effects of sulindac.

  19. CHARACTERIZATION OF THE METHIONINE SULFOXIDE REDUCTASES OF SCHISTOSOMA MANSONI

    PubMed Central

    Oke, Tolulope T.; Moskovitz, Jackob; Williams, David L.

    2013-01-01

    Schistosomiasis, also known as Bilharzia, is an infectious disease caused by several species of Schistosoma. Twenty million individuals suffer severe symptoms and 200,000 people die annually from the disease. The host responds to the presence of S. mansoni by producing reactive oxygen species that cause oxidative stress. We hypothesized that schistosomes produce antioxidants in response to oxidative stress. A known antioxidant protein is methionine sulfoxide reductase (Msr). Methionine residues can be oxidized to methionine sulfoxide in the presence of oxidizing agents, which is readily reversed by the action of the Msr system. Two S. mansoni MsrB genes (MsrB1 and MsrB2) were cloned and the recombinant proteins expressed in bacteria and purified. The S. mansoni MsrB proteins contained the common conserved catalytic and zinc coordinating cysteines. Analysis of the proteins showed that both proteins promote the reduction of both free methionine sulfoxide (Met[O]) and dabsyl-Met(O) to free methionine (Met) and dabsyl-Met, respectively, while exhibiting differences in their specific activities towards these substrates. Using real-time PCR, both proteins were found to be expressed in all stages of the parasite’s life cycle with the highest level of expression of both proteins in the egg stage. This is the first description of MsrB proteins from a parasite. PMID:19604033

  20. Photoinduced conformational switch of enantiopure azobenzenes controlled by a sulfoxide.

    PubMed

    Carreño, M Carmen; García, Isabel; Núñez, Irene; Merino, Estíbaliz; Ribagorda, María; Pieraccini, Silvia; Spada, Gian Piero

    2007-06-06

    Two series of enantiopure azobenzenes with a p-tolylsulfoxide at the ortho or meta position with respect to the azo group, have been regioselectively synthesized. Both can act as enantiopure molecular switches showing different structural features owing to the presence of the stereogenic sulfur. The photoisomerization process, studied by UV-vis, circular dichroism (CD), NMR, and chiral HPLC evidenced a double role of the sulfoxide. A transfer of chirality from the sulfoxide to the azo system was observed by CD in both cis and trans-isomers of the meta sulfinyl derivatives 3, whereas this perturbation was evident for the ortho sulfinyl series 7 only in the cis isomer. The NMR study evidenced that the s-cis rigid conformation of the bisaromatic sulfoxide was fixing a different orientation of the overall system in each series both in the trans and cis isomers, by forcing a final U-shaped structure in cis-3 and an S-shaped structure in cis-7. Very different values of specific optical rotations were measured in both trans and cis isomers, also reflecting the existence of distinct chiral entities in the photostationary states. The easy and reversible changes occurring between different conformational states could find applications in the photocontrol of several molecular switches.

  1. Resolution of a disputed albendazole result in the UK Official Control System - time for more guidance?

    PubMed

    Walker, Michael; Gray, Kirstin; Hopley, Christopher; Mussell, Christopher; Clifford, Louise; Meinerikandathevan, Jayanie; Firpo, Leonardo; Topping, Joanna; Santacruz, Daniel

    2017-04-01

    Albendazole, one of the benzimidazole anthelmintics, is used in ruminants and has maximum residue limits in muscle, fat and other tissue owing to reported teratogenicity. Albendazole is extensively metabolised in domestic animals and humans with rapid conversion to a sulphoxide and subsequently sulphone and amino sulphone metabolites. Sulphoxide metabolites are responsible for the systemic biological activity of benzimidazole drugs. Herein we report a case of disputed results for albendazole in a consignment sampled at import in which the Official Analyst certified against the consignment for excess albendazole. A laboratory acting for the importer reported data below the MRL, including a finding of the parent drug which is not included in the residue definition. The Government Chemist has a statutory duty as a route of technical appeal in the UK Official Food Control system and the case was referred for referee analysis. We report our findings based on a LC-MS/MS method, which confirmed the official findings, did not reveal the presence of the parent drug but identified hot spots of albendazole marker residues in the consignment. We discuss the need for recommendations on official sampling at import and interpretation of results.

  2. Environmental behavior of benalaxyl and furalaxyl enantiomers in agricultural soils.

    PubMed

    Qin, Fang; Gao, Yong X; Guo, Bao Y; Xu, Peng; Li, Jian Z; Wang, Hui L

    2014-01-01

    The enantioselective environmental behavior of the chiral fungicides benalaxy and furalaxyl in agricultural soils in China was studied. Although sorption onto soils was non-enantioselective, the leaching of benalaxy and furalaxyl was enantioselective in soil columns. The concentrations of the S-enantiomers of both fungicides in the leachates were higher than the R-enantiomers. This can be attributed to enantioselective degradation of the two fungicides in the soil column. Enantioselective degradation of the two fungicides was verified by soil dissipation experiments, and the R-enantiomers degraded faster than the S-enantiomers in partial soils. The half-life was 27.7-57.8 days for S-benalaxyl, 20.4-53.3 days for R-benalaxyl, 19.3-49.5 days for S-furalaxyl and 11.4-34.7 days for R-furalaxyl. The degradation process of the two fungicide enantiomers followed the first-order kinetics (R(2) > 0.96). Compared to furalaxyl, benalaxyl degraded more slowly and degradation was less enantioselective. These results are attributed to the influence of soil physicochemical properties, soil microorganisms, and environmental factors.

  3. #2) Enantiomer Specific Measurements of Current-use ...

    EPA Pesticide Factsheets

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide enantiomers is dictated by the formulation (e.g., racemic or enriched), transport and degradation rates (usually stereoselective if biotic, non-selective if abiotic) which can vary between the mirror images. We developed a new GC/MS method for stereoisomer-specific analysis of the current-use pesticides fipronil, cis-bifenthrin, cis-permethrin, cypermethrin, and cyfluthrin. Single enantiomer standards were obtained for the first four compounds to allow a direct link to enantiomer toxicity. The method was applied to several different sets of extracts including lab dosed salmon and various environmental media (concrete runoff, sediment, river-, surface-, storm-, and waste- water) that were collected from California aquatic systems. Enantiomer fractions (EFs) for racemic standards ranged from 0.351 to 0.592 for fipronil, 0.457 to 0.521 for bifenthrin, and 0.429 to 0.525 for cis-permethrin. At least in part due to the wide range, EFs for most environmental samples were the same as racemic standards. An interesting exception was for permethrin washed off of concrete, which had EFs ranging from 0.094 to 0.502. As expected, the biological fish samples (dosed with bifenthrin) were also non-race

  4. Odour character differences for enantiomers correlate with molecular flexibility

    PubMed Central

    Brookes, Jennifer C; Horsfield, A.P; Stoneham, A.M

    2008-01-01

    The olfactory system sensitively discerns scents from many small molecules as the brain analyses signals from nasal receptors. These receptors are selective to some degree, though the mechanism for selectivity is still controversial. Enantiomers, chiral pairs of left- and right-handed structures, are an important class of molecules in assessing proposed mechanisms. We show that there is a correlation between molecular (structural) flexibility and whether or not the left- and right-handed enantiomers smell the same. In particular, for the fairly extensive class of enantiomers with six-membered ring flexibility, enantiomers do not smell the same. There are, of course, significant experimental uncertainties, which we discuss here. We discuss models of receptor selectivity, both those based on shape and those where discrimination is based on other factors, such as electron affinity, proton affinity or vibration frequencies. The differences in scent of these enantiomers appear to be consistent with simple generalizations of a ‘swipe card’ model in which, while the shape must be good enough, critical information for actuation is a separate factor. PMID:18595834

  5. An insect growth inhibitor--lufenuron--enhances albendazole activity against hydatid cyst.

    PubMed

    Breijo, Martín; Isnardi, Fernanda; Brauer, Mónica; Schenker, Rudolf; Ferrari, Mariana; Ferreira, Ana M

    2011-09-27

    The aim of this work was to evaluate the potential of lufenuron, a benzylphenylurea with ability to interfere with the formation of insect exoskeleton, as a therapeutic drug for larval echinococcosis (hydatid disease). For this purpose lufenuron, alone or in combination with albendazole, was administered to CD1 mice bearing Echinococcus granulosus hydatid cysts in the peritoneal cavity. Neither of the drugs alone was able to exert parasiticidal effects. However, in combination with albendazole, lufenuron reduced the growth of cysts (30-40% in cyst diameter respect to control, p<0.05). This effect was associated with ultrastructural alterations of the hydatid cyst wall and a reduction of the content of myo-inositol-hexakisphosphate, the major component of the electron dense granules of the laminated layer. Overall, this work provides evidence that lufenuron could represent a useful compound for the use in chemotherapy against larval echinococcosis, by enhancing albendazole parasiticidal activity.

  6. Influence of glutamic acid enantiomers on C-mineralization.

    PubMed

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

    Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils from selected ecosystems was determined and subjected to a range of treatments: ambient x elevated CO2 level and meadow x dense x thinned forest environment. Mineralization of glutamic acid was determined by incubation of the soil with 2 mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the course of a vegetation season, following a similar trend across a range of ecosystems. Mineralization is affected by environmental changes and management practices, including elevated CO2 level and thinning intensity. L-glutamic acid metabolism is more dependent on soil type as compared to metabolism of its D-enantiomer. The results support the hypothesis that the slower rate of D- compared to L- amino acid mineralization is due to different roles in anabolism and catabolism of the soil microbial community.

  7. Adsorption geometry of propranolol enantiomers on silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Stiufiuc, Rares; Iacovita, Cristian; Lucaciu, Constantin M.; Stiufiuc, Gabriela; Nicoara, Raul; Oltean, Mircea; Chis, Vasile; Bodoki, Ede

    2013-01-01

    In the present work we report an experimental and theoretical study on propranolol a widely used beta-blocking drug. Raman and Surface Enhanced Raman Spectroscopies (SERSs) have been employed for the detection of the molecular vibrations, while quantum chemical calculations based on density functional theory (DFT) have been used to determine the geometrical, energetic and vibrational characteristics of propranolol. Using a 785 nm laser line, the SERS spectra of the two propranolol enantiomers adsorbed on hydroxylamine reduced silver colloids have been measured in the 3-11 pH range. Based on DFT calculations performed at the B3LYP level of theory the FT-IR, Raman and SERS spectra of propranolol enantiomers were assigned. The adsorption geometry of both enantiomers onto the silver surface was predicted using the calculated molecular electrostatic potential (MEP) in association with data obtained from SERS.

  8. [Ascariasis: comparison of the therapeutic efficacy between paico and albendazole in children from Huaraz].

    PubMed

    López De Guimaraes, D; Neyra Llanos, R S; Romero Acevedo, J H

    2001-01-01

    A therapeutical clinical trial was designed to study the effectiveness of Paico and Albendazole, for the treatment of ascariasis in a group of 60 children, between 3 and 14 years old, from a rural community in Huaraz. It was carried out between May and August, 2000. The sample was randomly divided into 30 cases for Paico and 30 for Albendazole, the criteria for entering the trial being a positive examination for Ascaris lumbricoides in feces. The treatment consisted in Paico juice: 1 ml/Kg for less than 10 Kg, and 2 ml/Kg in larger children, one dose before breakfast, for three consecutive days. The Albendazole was administered in a single dose of 400 mg in those over five years of age, and 200 mg in younger children. The effectiveness was evaluated qualitatively (the disappearance of the ascaris eggs from the feces) and quantitatively (decrease in the parasitic burden); in the stool examinations carried out in all cases on entering the study and 15 days after the treatment. All the stool samples were processed in the Referential Laboratory of the Regional Health Authority in Ancash. The qualitative effectiveness between Paico and Albendazole for the eradication of ascariasis was similar at 86.7%. The quantitative effectiveness was 59.5% for Paico and 58.3% for Albendazole. However, it was observed that, unlike Albedazole, Paico is 100% effective in the treatment of Hymenolepsis nana. Adverse effects were presented in 23.3% of the cases for both drugs. It is concluded that, although Paico and Albendazole have a similar effectiveness against Ascaris lumbricoides, Paico has the additional benefit of being effective against Hymenolepsis nana.

  9. Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography.

    PubMed

    Wistuba, D; Schurig, V

    2000-04-14

    Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography (CEC) is achieved with open-tubular capillaries (o-CEC), with packed capillaries (p-CEC) or with monolithic capillaries. In o-CEC, capillaries are coated with a thin film containing cyclodextrin derivatives, cellulose, proteins, poly-terguride or molecularly imprinted polymers as chiral selectors. In p-CEC, typical chiral HPLC stationary phases such as silica-bonded cyclodextrin or cellulose derivatives, proteins, glycoproteins, macrocyclic antibiotics, quinine-derived and 'Pirkle' selectors, polyacrylamides and molecularly imprinted polymers are used as chiral selectors. Chiral monolithic stationary phases prepared by in situ polymerization into the capillary were also developed for electrochromatographic enantiomer separation.

  10. Simplified Production of Organic Compounds Containing High Enantiomer Excesses

    NASA Technical Reports Server (NTRS)

    Cooper, George W. (Inventor)

    2015-01-01

    The present invention is directed to a method for making an enantiomeric organic compound having a high amount of enantiomer excesses including the steps of a) providing an aqueous solution including an initial reactant and a catalyst; and b) subjecting said aqueous solution simultaneously to a magnetic field and photolysis radiation such that said photolysis radiation produces light rays that run substantially parallel or anti-parallel to the magnetic field passing through said aqueous solution, wherein said catalyst reacts with said initial reactant to form the enantiomeric organic compound having a high amount of enantiomer excesses.

  11. Chromatographic Separations of Enantiomers and Underivatized Oligosaccharides

    SciTech Connect

    Liu, Ying

    2004-01-01

    My graduate research has focused on separation science and bioanalytical analysis, which emphasized in method development. It includes three major areas: enantiomeric separations using high performance liquid chromatography (HPLC), Super/subcritical fluid chromatography (SFC), and capillary electrophoresis (CE); drug-protein binding behavior studies using CE; and carbohydrate analysis using liquid chromatograph-electrospray ionization mass spectrometry (LC-ESI-MS). Enantiomeric separations continue to be extremely important in the pharmaceutical industry. An in-depth evaluation of the enantiomeric separation capabilities of macrocyclic glycopeptides CSPs with SFC mobile phases was investigated using a set of over 100 chiral compounds. It was found that the macrocyclic based CSPs were able to separate enantiomers of various compounds with different polarities and functionalities. Seventy percent of all separations were achieved in less than 4 min due to the high flow rate (4.0 ml/min) that can be used in SFC. Drug-protein binding is an important process in determining the activity and fate of a drug once it enters the body. Two drug/protein systems have been studied using frontal analysis CE method. More sensitive fluorescence detection was introduced in this assay, which overcame the problem of low sensitivity that is common when using UV detection for drug-protein studies. In addition, the first usage of an argon ion laser with 257 nm beam coupled with CCD camera as a frontal analysis detection method enabled the simultaneous observation of drug fluorescence as well as the protein fluorescence. LC-ESI-MS was used for the separation and characterization of underivatized oligosaccharide mixtures. With the limits of detection as low as 50 picograms, all individual components of oligosaccharide mixtures (up to 11 glucose-units long) were baseline resolved on a Cyclobond I 2000 column and detected using ESI-MS. This system is characterized by high chromatographic

  12. TOXICITY OF FIPRONIL ENANTIOMERS TO THE WATER FLEA AND BLACK FLY

    EPA Science Inventory

    In this research, we analyzed the enantiomer-specific toxicity of fipronil using two aquatic invertebrate species. Acute toxicity to Ceriodaphnia dubia (water flea) indicated that the (+) enantiomer was significantly more toxic than the (-) enantiomer, with about a 3-fold differ...

  13. Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

    PubMed

    Ismail, M M; Jayakody, R L; Weil, G J; Fernando, D; De Silva, M S; De Silva, G A; Balasooriya, W K

    2001-01-01

    In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.

  14. FATE AND EFFECTS OF THE ENANTIOMERS OF CHIRAL ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    Enantiomers, the mirror image isomers of chiral compounds, are known to be selective in their interaction with other chiral molecules, including enzymes and other biochemicals. This holds true for pesticides, about 25% of which are chiral molecules, and other chiral environmental...

  15. Optimization of preparative electrophoretic chiral separation of ritalin enantiomers.

    PubMed

    Schneiderman, Eva; Gratz, Samuel R; Stalcup, Apryll M

    2002-01-15

    Continuous free flow electrophoresis (CFFE) was applied to the preparative chiral separation of ritalin enantiomers. Sulfated beta-cyclodextrin (sbeta-CD) was used as the chiral additive. Liquid chromatography-mass spectrometry (LC-MS) experiments were applied to study the time averaged concentration of sbeta-CD in the separation chamber. The distribution of sbeta-CD in the separation chamber greatly influenced resolution and the angle of deflection. To optimize the separation, several parameters (methanol, concentration of sbeta-CD in the cathodic wash and in the separation buffer, and the introduction of a low conductivity zone) were investigated. The dependence of the resolution and deflection angles of ritalin enantiomers on the concentration of sbeta-CD in both the separation buffer and in the cathode wash solution appeared to be non-linear. Under close to optimal conditions, resolution of ritalin enantiomers was about 0.8 with an average processing rate of 0.5 mg/h. Overall, the enantiomeric purity of the individual isomers was approximately 83%; however, of the 20 vials containing ritalin, the presence of both enantiomers was only detected in three vials.

  16. THE ENANTIOMERS OF CHIRAL POLLUTANTS POSE DIFFERENT RISKS

    EPA Science Inventory

    In order to make more accurate risk assessments for chiral pesticides and other pollutants, it is necessary to understand the relative persistence and effects of their enantiomers. A major effort is underway in the USEPA to measure exposure in the home environment to various pes...

  17. The real gordian knot: racemic mixtures versus pure enantiomers.

    PubMed

    Szelenyi, I; Geisslinger, G; Polymeropoulos, E; Paul, W; Herbst, M; Brune, K

    1998-04-01

    Many drugs exist as asymmetric three-dimensional (chiral) molecules and will therefore have several stereoisomers. There are often pharmacodynamic, pharmacokinetic and/or toxicological differences between enantiomers. The choice between developing a racemate or single enantiomers depends on therapeutic advances and developmental costs involved. Regarding the target environment for drug intervention, even if natural physiological mediators are achiral, their receptors may demonstrate a preference for the (-)- or (+)-enantiomer of agonists or antagonists. It is also obvious that the majority of enzymes and channels are stereospecific, at least to a variable extent. From a pharmacokinetics point of view, chirality can have an influence on drug absorption, distribution, metabolism and elimination. With a few exceptions, toxicological differences between isomers of known drugs are less dramatic than thought to be and only seldom substantiate the necessity of a racemic switch. The pharmaceutical industry is currently very interested in the so-called "racemic switch." Before proceeding to a racemic switch it is necessary to determine if 1) it is chemically feasible to produce a single enantiomer; 2) a clinical advantage is obtainable through a racemic switch; and 3) a marketing advantage is obtainable. The real goal of a racemic switch should be the rational development of compounds that are profitable for the company and--first of all--beneficial for the patient.

  18. Single-enantiomer drugs: elegant science, disappointing effects.

    PubMed

    Mansfield, Peter; Henry, David; Tonkin, Anne

    2004-01-01

    Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

  19. FT-IR SOLUTION SPECTRA OF PROPYL SULFIDE, PROPYL SULFOXIDE, AND PROPYL SULFONE

    EPA Science Inventory

    FT-IR spectra were obtained of 0.5% volumetric solutions of propyl sulfide, propyl sulfoxide, and propyl sulfone in hexane, CCl4, CS2, and CHCl3 to assist in the assignment of FT-IR-PAS spectra of propyl sulfoxide sorbed within the structure of several peats and onto cellulose. T...

  20. Determination of the specific activities of methionine sulfoxide reductase A and B by capillary electrophoresis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A capillary electrophoresis (CE) method for the determination of methionine sulfoxide reductase A and methionine sulfoxide reductase B activities in mouse liver is described. The method is based on detection of the 4-(dimethylamino)azobenzene-4’-sulfonyl derivative of L-methionine (dabsyl Met), the ...

  1. SWELLING OF PEATS IN LIQUID METHYL, TETRAMETHYLENE AND PROPYL SULFOXIDES AND IN LIQUID PROPYL SULFONE

    EPA Science Inventory

    The interactions of methyl, tetramethylene, and propyl sulfoxides and propyl sulfone during sorption onto four de-waxed, acid-form peats have been studied by means of swelling measurements. The results for sulfoxides are displayed as het-eromolecular sorption isotherms, which plo...

  2. tert-Butyl Sulfoxide as a Starting Point for the Synthesis of Sulfinyl Containing Compounds.

    PubMed

    Wei, Juhong; Sun, Zhihua

    2015-11-06

    Sulfoxides bearing a tert-butyl group can be activated using N-bromosuccinimide (NBS) under acidic conditions and then subsequently treated with a variety of nitrogen, carbon, or oxygen nucleophiles to afford a wide range of the corresponding sulfinic acid amides, new sulfoxides, and sulfinic acid esters.

  3. The natural history of cystic echinococcosis in untreated and albendazole-treated patients.

    PubMed

    Solomon, N; Kachani, M; Zeyhle, E; Macpherson, C N L

    2017-03-21

    The World Health Organization (WHO) treatment protocols for cystic echinococcosis (CE) are based on the standardized ultrasound (US) classification. This study examined whether the classification reflected the natural history of CE in untreated and albendazole-treated patients. Data were collected during mass US screenings in CE endemic regions among transhumant populations, the Turkana and Berber peoples of Kenya and Morocco. Cysts were classified using the WHO classification. Patient records occurring prior to treatment, and after albendazole administration, were selected. 852 paired before/after observations of 360 cysts from 257 patients were analyzed. A McNemar-Bowker χ(2) test for symmetry was significant (p<0.0001). 744 observations (87.3%) maintained the same class, and 101 (11.9%) progressed, consistent with the classification. Regression to CE3B occurred in seven of 116 CE4 cyst observations (6.0%). A McNemar-Bowker χ(2) test of 1414 paired before/after observations of 288 cysts from 157 albendazole-treated patients was significant (p<0.0001). 1236 observations (87.4%) maintained the same class, and 149 (10.5%) progressed, consistent with the classification. Regression to CE3B occurred in 29 of 206 CE4 observations (14.1%). Significant asymmetry confirms the WHO classification's applicability to the natural history of CE and albendazole-induced changes. Regressions may reflect the stability of CE3B cysts.

  4. Effectiveness Evaluation of Levamisole, Albendazole, Ivermectin, and Vernonia amygdalina in West African Dwarf Goats

    PubMed Central

    Adediran, Oyeduntan A.; Uwalaka, Emmanuel C.

    2015-01-01

    Anthelmintic drug resistance has led to the search for alternatives in controlling helminth infections. Fifty West African Dwarf goats without history of anthelmintic treatment were divided equally into five groups. Group A was treated with ivermectin injection subcutaneously, group B with levamisole subcutaneously, group C with albendazole orally, and group D with aqueous extract of Vernonia amygdalina and group E was untreated control. Faecal samples were collected before treatment from each animal and larval culture was carried out. Faecal egg count reduction (FECR) test was carried out for each group and the data analysed using FECR version 4 to calculate percent reduction in faecal egg count. Predominant helminth infections from larval culture were Haemonchus contortus (70%), Trichostrongylus spp. (61%), and Oesophagostomum spp. (56%). Mixed infection was present in all the animals. From the FECR test Vernonia amygdalina extract was more effective against helminths (100%), compared to ivermectin 96%, levamisole 96%, and albendazole 99%. The lower 95% confidence limit was 89 for ivermectin and levamisole and 91 for albendazole. There is low resistance to ivermectin and levamisole and susceptibility to albendazole while V. amygdalina has great potentials that could be explored for the treatment of helminth diseases in goats. PMID:26579232

  5. Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti.

    PubMed

    Dreyer, Gerusa; Addiss, David; Williamson, John; Norões, Joaquim

    2006-12-01

    Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n=25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n=22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P=0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P=0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.

  6. Identification of activators of methionine sulfoxide reductases A and B

    PubMed Central

    Cudic, Predrag; Joshi, Neelambari; Sagher, Daphna; Williams, Brandon T.; Stawikowski, Maciej J.; Weissbach, Herbert

    2016-01-01

    The methionine sulfoxide reductase (Msr) family of enzymes has been shown to protect cells against oxidative damage. The two major Msr enzymes, MsrA and MsrB, can repair oxidative damage to proteins due to reactive oxygen species, by reducing the methionine sulfoxide in proteins back to methionine. A role of MsrA in animal aging was first demonstrated in D. melanogaster where transgenic flies over-expressing recombinant bovine MsrA had a markedly extended life span. Subsequently, MsrA was also shown to be involved in the life span extension in C. elegans. These results supported other studies that indicated up-regulation, or activation, of the normal cellular protective mechanisms that cells use to defend against oxidative damage could be an approach to treat age related diseases and slow the aging process. In this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB. PMID:26718410

  7. Lithium solvation in dimethyl sulfoxide-acetonitrile mixtures

    SciTech Connect

    Semino, Rocío; Zaldívar, Gervasio; Calvo, Ernesto J.; Laria, Daniel

    2014-12-07

    We present molecular dynamics simulation results pertaining to the solvation of Li{sup +} in dimethyl sulfoxide-acetonitrile binary mixtures. The results are potentially relevant in the design of Li-air batteries that rely on aprotic mixtures as solvent media. To analyze effects derived from differences in ionic size and charge sign, the solvation of Li{sup +} is compared to the ones observed for infinitely diluted K{sup +} and Cl{sup −} species, in similar solutions. At all compositions, the cations are preferentially solvated by dimethyl sulfoxide. Contrasting, the first solvation shell of Cl{sup −} shows a gradual modification in its composition, which varies linearly with the global concentrations of the two solvents in the mixtures. Moreover, the energetics of the solvation, described in terms of the corresponding solute-solvent coupling, presents a clear non-ideal concentration dependence. Similar nonlinear trends were found for the stabilization of different ionic species in solution, compared to the ones exhibited by their electrically neutral counterparts. These tendencies account for the characteristics of the free energy associated to the stabilization of Li{sup +}Cl{sup −}, contact-ion-pairs in these solutions. Ionic transport is also analyzed. Dynamical results show concentration trends similar to those recently obtained from direct experimental measurements.

  8. A clinical and microbiological study on the enantiomers of delmopinol.

    PubMed

    Sjödin, Torgny; Nilner, Krister; Sparre, Birgitta; Bernet, Catarina; Åström, Mikael

    2016-07-01

    Objective The clinical part of this study aimed to investigate whether the racemate of delmopinol [(±)-delmopinol] is equivalent to its two enantiomers [(+)-delmopinol and (-)-delmopinol] with respect to efficiency and to determine and compare their pharmacokinetic properties. The purpose of the pre-clinical part was to elucidate possible differences in antimicrobial efficiency. Materials and methods The compounds were tested clinically in a double-blind, randomized, cross-over study comprising three treatment periods of 4 days each. The antimicrobial efficacy of the enantiomers was compared in vitro with respect to planktonic and biofilm bacteria of different species. Results No statistically significant differences in prevention of plaque formation were observed. Except for a somewhat higher systemic exposure in terms of AUC and Cmax indicated for (-)-delmopinol compared to (+)-delmopinol, the pharmacokinetic properties were similar. The most common adverse event was a transient anaesthetic feeling in the mouth. This event was reported with the same frequency for all three test solutions. The enantiomers showed similar antimicrobial effects on planktonic bacteria and their biofilms. Conclusions The enantiomers were found to be equally effective with respect to inhibition of plaque development and only minor differences were observed with respect to their pharmacokinetic properties. No differences could be observed in the adverse events reports. There is, therefore, no reason to use one of the enantiomers of delmopinol instead of the racemate. This was further supported by the antimicrobial tests. It is suggested that the combined action of cationic and neutral delmopinol is important for its effect on biofilms.

  9. Enantioselective DNA condensation induced by heptameric lanthanum helical supramolecular enantiomers.

    PubMed

    Bao, Fei-Fei; Xu, Xin-Xin; Zhou, Wen; Pang, Chun-Yan; Li, Zaijun; Gu, Zhi-Guo

    2014-09-01

    DNA condensation induced by a pair of heptameric La(III) helical enantiomers M-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O and P-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O (M-La and P-La, L=2-(2-hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and SEM. The enantiomers M-La and P-La could induce CT-DNA condensation at a low concentration as observed in UV/vis spectroscopy. DNA condensates possessed globular nanoparticles with nearly homogeneous sizes in solid state determined by SEM (ca. 250 nm for M-La and ca. 200 nm for P-La). The enantiomers bound to DNA through electrostatic attraction and hydrogen bond interactions in a major groove, and rapidly condensed free DNA into its compact state. DNA decompaction has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M-La and P-La displayed discernible discrimination in DNA interaction and DNA condensation, as well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M-La and P-La were efficient DNA packaging agents with potential applications in gene delivery.

  10. Stereoselective analysis of thioridazine-2-sulfoxide and thioridazine-5-sulfoxide: an investigation of rac-thioridazine biotransformation by some endophytic fungi.

    PubMed

    Borges, Keyller Bastos; De Souza Borges, Warley; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

    2008-04-14

    The purpose of this study was to develop a method for the stereoselective analysis of thioridazine-2-sulfoxide (THD-2-SO) and thioridazine-5-sulfoxide (THD-5-SO) in culture medium and to study the biotransformation of rac-thioridazine (THD) by some endophytic fungi. The simultaneous resolution of THD-2-SO and THD-5-SO diastereoisomers was performed on a CHIRALPAK AS column using a mobile phase of hexane:ethanol:methanol (92:6:2, v/v/v)+0.5% diethylamine; UV detection was carried out at 262 nm. Diethyl ether was used as extractor solvent. The validated method was used to evaluate the biotransformation of THD by 12 endophytic fungi isolated from Tithonia diversifolia, Viguiera arenaria and Viguiera robusta. Among the 12 fungi evaluated, 4 of them deserve prominence for presenting an evidenced stereoselective biotransformation potential: Phomopsis sp. (TD2) presented greater mono-2-sulfoxidation to the form (S)-(SE) (12.1%); Glomerella cingulata (VA1) presented greater mono-5-sulfoxidation to the forms (S)-(SE)+(R)-(FE) (10.5%); Diaporthe phaseolorum (VR4) presented greater mono-2-sulfoxidation to the forms (S)-(SE) and (R)-(FE) (84.4% and 82.5%, respectively) and Aspergillus fumigatus (VR12) presented greater mono-2-sulfoxidation to the forms (S)-(SE) and (R)-(SE) (31.5% and 34.4%, respectively).

  11. Effect of albendazole administration on pharmacokinetic aspects of tylosin in lactating goats.

    PubMed

    Atef, M; Ramadan, A; Darwish, A S; Fahim, Aisha M M

    2009-08-01

    Tylosin concentrations and its disposition kinetics in serum, urine, and milk of lactating goats following a single intravenous (i.v.) or intramuscular (i.m.) injection (10 mg kg(-1) b.wt.) were carried out using high performance liquid chromatography (HPLC).The concentration-time curve of tylosin after i.v. injection could be described by a two-compartment open model. Tylosin was rapidly distributed and eliminated from goat's bodies with t(1/2(beta)) value of 1.25 h. The V((d)) was less than one litre/kg and the MRT was 1.40 h. Concomitant administration with albendazole decreased tylosin concentrations in serum after its i.v. injection and the MRT was 1.17 h. The AUC and AUMC showed a significant decrease in goats given albendazole prior to injection as compared with those given tylosin only. Following i.m. administration, the absorption half-life and the corresponding t(max) revealed rapid absorption rate with systemic bioavailability (F%) of 76.2 %. Albendazole when given concurrently with tylosin decreased its serum concentrations due to lower bioavailability (43.25 %). Following i.v. or i.m. injection, tylosin was excreted rapidly in urine in concentration much higher than those determined in serum and milk. Tylosin administered in goats pretreated with albendazole was excreted at lower concentration in urine, with a significant decrease from 1(st) to 10(th) hours as compared with animals given tylosin only. Following i.v. or i.m. administration of tylosin, the drug was excreted in high concentrations in milk. A significant decrease in milk concentrations was reported in goats pretreated with albendazole.

  12. Efficacy of single-dose diethylcarbamazine compared with diethylcarbamazine combined with albendazole against Wuchereria bancrofti infection in Papua New Guinea.

    PubMed

    Bockarie, Moses J; Tavul, Livingstone; Ibam, Irvin; Kastens, Will; Hazlett, Fred; Tisch, Daniel J; Alpers, Michael P; Kazura, James W

    2007-01-01

    The efficacy of diethylcarbamazine alone was compared with diethylcarbamazine plus albendazole in residents of an island in Papua New Guinea endemic for Wuchereria bancrofti. There was no statistically significant difference between the two drug regimens in decreasing the microfilaria positive rate at 12 and 24 months after a single-dose treatment with either regimen, e.g., 50.0% clearance of microfilaria at 24 months for diethylcarbamazine alone versus 65.7% clearance of microfilaria for diethylcarbamazine plus albendazole (P > 0.05). In contrast, diethylcarbamazine plus albendazole resulted in a significant decrease in Og4C3 antigen prevalence (17%; P = 0.003) at 24 months whereas diethylcarbamazine did not (10%; P = 0.564). These data showed no statistically significant difference in the efficacy of the two drug regimens in lowering the microfilaria reservoir, but they support the use of diethylcarbamazine combined with albendazole in mass treatment programs on the basis of greater activity against adult worms.

  13. Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

    PubMed

    Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

    2016-09-01

    An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.

  14. Bisguanidinium dinuclear oxodiperoxomolybdosulfate ion pair-catalyzed enantioselective sulfoxidation

    PubMed Central

    Zong, Lili; Wang, Chao; Moeljadi, Adhitya Mangala Putra; Ye, Xinyi; Ganguly, Rakesh; Li, Yongxin; Hirao, Hajime; Tan, Choon-Hong

    2016-01-01

    Catalytic use of peroxomolybdate for asymmetric transformations has attracted increasing attention due to its catalytic properties and application in catalysis. Herein, we report chiral bisguanidinium dinuclear oxodiperoxomolybdosulfate [BG]2+[(μ-SO4)Mo2O2(μ-O2)2(O2)2]2− ion pair, as a catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation of a range of dialkyl sulfides. The practical utility was illustrated using a gram-scale synthesis of armodafinil, a commercial drug, with the catalyst generated in situ from 0.25 mol% of bisguanidinium and 2.5 mol% of Na2MoO4·2H2O. Structural characterization of this ion pair catalyst has been successfully achieved using single-crystal X-ray crystallography. PMID:27869124

  15. Supported oligomethionine sulfoxide and Ellman's reagent for cysteine bridges formation.

    PubMed

    Ronga, Luisa; Verdié, Pascal; Sanchez, Pierre; Enjabal, Christine; Maurras, Amélie; Jullian, Magalie; Puget, Karine; Martinez, Jean; Subra, Gilles

    2013-02-01

    A large number of bioactive peptides are cyclized through a disulfide bridge. This structural feature is very important for both bioactivity and stability. The oxidation of cysteine side chains is challenging not only to avoid intermolecular reaction leading to oligomers and oxidation of other residues but also to remove solvents and oxidant such as dimethyl sulfoxide. Supported reagents advantageously simplify the work-up of such disulfide bond formation, but may lead to a significant decrease in yield of the oxidized product. In this study, two resins working through different mechanisms were evaluated: Clear-Ox, a supported version of Ellman's reagent and Oxyfold, consisting in a series of oxidized methionine residues. The choice of the supported reagent is discussed on the light of reaction speed, side-products formation and yield considerations.

  16. Bisguanidinium dinuclear oxodiperoxomolybdosulfate ion pair-catalyzed enantioselective sulfoxidation

    NASA Astrophysics Data System (ADS)

    Zong, Lili; Wang, Chao; Moeljadi, Adhitya Mangala Putra; Ye, Xinyi; Ganguly, Rakesh; Li, Yongxin; Hirao, Hajime; Tan, Choon-Hong

    2016-11-01

    Catalytic use of peroxomolybdate for asymmetric transformations has attracted increasing attention due to its catalytic properties and application in catalysis. Herein, we report chiral bisguanidinium dinuclear oxodiperoxomolybdosulfate [BG]2+[(μ-SO4)Mo2O2(μ-O2)2(O2)2]2- ion pair, as a catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation of a range of dialkyl sulfides. The practical utility was illustrated using a gram-scale synthesis of armodafinil, a commercial drug, with the catalyst generated in situ from 0.25 mol% of bisguanidinium and 2.5 mol% of Na2MoO4.2H2O. Structural characterization of this ion pair catalyst has been successfully achieved using single-crystal X-ray crystallography.

  17. Effects of dimethyl sulfoxide on lipid membrane electroporation.

    PubMed

    Fernández, M Laura; Reigada, Ramon

    2014-08-07

    Pores can be generated in lipid membranes by the application of an external electric field or by the addition of particular chemicals such as dimethyl sulfoxide (DMSO). Molecular dynamics (MD) has been shown to be a useful tool for unveiling many aspects of pore formation in lipid membranes in both situations. By means of MD simulations, we address the formation of electropores in cholesterol-containing lipid bilayers under the influence of DMSO. We show how a combination of physical and chemical mechanisms leads to more favorable conditions for generating membrane pores and, in particular, how the addition of DMSO to the medium significantly reduces the minimum electric field required to electroporate a lipid membrane. The strong alteration of membrane transversal properties and the energetic stabilization of the hydrophobic pore stage by DMSO provide the physicochemical mechanisms that explain this effect.

  18. Transformation and adsorption of Fenamiphos, f. sulfoxide and f. sulfone in molokai soil and simulated movement with irrigation

    NASA Astrophysics Data System (ADS)

    Lee, Chee-Chow; Green, Richard E.; Apt, Walter J.

    1986-02-01

    The ban of commonly used soil fumigants, DBCP and EDB, for control of nematodes in pineapple fields has prompted investigations into a non-fumigant nematicide, fenamiphos (Nemacur ®). The transformation and adsorption in soil of fenamiphos and its transformation products, f. sulfoxide and f. sulfone were studied in the laboratory. Fenamiphos adsorption on soil exceeded that of f. sulfoxide and f. sulfone. F. sulfoxide, however, was the most persistent. A one-dimensional simulation model was used to assess the impact of transformation and adsorption on the mobility and distribution of fenamiphos and f. sulfoxide in soil. Simulated results showed that fenamiphos stayed in the topsoil and transformed rapidly to f. sulfoxide. Because of the persistence and mobility of f. sulfoxide, this metabolite leached rapidly and significant amounts remained in the soil. This suggests that for times exceeding three weeks, f. sulfoxide may be the dominant compound providing nematode control in drip-irrigated pineapple.

  19. Resolving enantiomers using the optical angular momentum of twisted light

    PubMed Central

    Brullot, Ward; Vanbel, Maarten K.; Swusten, Tom; Verbiest, Thierry

    2016-01-01

    Circular dichroism and optical rotation are crucial for the characterization of chiral molecules and are of importance to the study of pharmaceutical drugs, proteins, DNA, and many others. These techniques are based on the different interactions of enantiomers with circularly polarized components of plane wave light that carries spin angular momentum (SAM). For light carrying orbital angular momentum (OAM), for example, twisted or helical light, the consensus is that it cannot engage with the chirality of a molecular system as previous studies failed to demonstrate an interaction between optical OAM and chiral molecules. Using unique nanoparticle aggregates, we prove that optical OAM can engage with materials’ chirality and discriminate between enantiomers. Further, theoretical results show that compared to circular dichroism, mainly based on magnetic dipole contributions, the OAM analog helical dichroism (HD) is critically dependent on fundamentally different chiral electric quadrupole contributions. Our work opens new venues to study chirality and can find application in sensing and chiral spectroscopy. PMID:26998517

  20. Chirality detection of enantiomers using twisted optical metamaterials

    PubMed Central

    Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

    2017-01-01

    Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies. PMID:28120825

  1. Chirality detection of enantiomers using twisted optical metamaterials

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

    2017-01-01

    Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies.

  2. Pharmacokinetics of terazosin enantiomers in healthy Chinese male subjects.

    PubMed

    Liu, Man; Zhang, Dan; Yang, Man; Zhao, Ting; Wang, Xiaolin; Zhang, Yanan; Han, Jing; Liu, Huichen

    2012-12-01

    The purpose of this study was to elucidate the pharmacokinetics of terazosin enantiomers in healthy Chinese male subjects. After a single oral dose of 2-mg terazosin, the plasma concentrations of terazosin enantiomers were measured over the course of 48 h in 12 healthy subjects. The plasma concentrations of (+)-(R)-terazosin at all time points were higher than those of (-)-(S)-terazosin. The area under the plasma concentration-time curve (AUC(0-∞) ) and maximum plasma concentration of (+)-(R)-terazosin were significantly greater than those of the (-)-(S)-terazosin (P < 0.01, respectively). The R/S ratio of AUC(0-∞) of terazosin was 1.68. For the first time, it was proven that the pharmacokinetics of terazosin was stereoselective in healthy Chinese male subjects.

  3. Chiral Recognition Mechanisms in Enantiomers Separations: A General View

    NASA Astrophysics Data System (ADS)

    Berthod, Alain

    In 1858, Louis Pasteur, the first to accomplish the separation of two enantiomers wrote: “Most natural organic products, the essential products of life, are asymmetric and possess such asymmetry that they are not superimposable on their image. This establishes perhaps the only well-marked line of demarcation that can at present be drawn between the chemistry of dead matter and the chemistry of living matter.” Enantiomers have exactly the same properties in isotropic conditions. They behave differently only in anisotropic conditions. Chiral-chiral interactions are needed for enantiomeric separations. The fundamental mechanisms for chiral separations are listed along with the commercially available chiral selectors. Two chemometric examples are commented: one on quantitative structure enantioselectivity relationship and the second one on linear solvation energy relationships. It is shown that the solvents used in the mobile phase may play the most critical role in the chiral mechanism.

  4. Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole

    PubMed Central

    Qavi, Abdul; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Kumar, Neeraj; Malhotra, Kiran Preet; Srivastava, Pradeep Kumar; Verma, Rajesh; Sharma, Praveen Kumar

    2016-01-01

    Abstract In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India. Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available. There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment. Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in

  5. Distribution of zirconium in petroleum sulfoxides during extraction and sorption from nitric and hydrochloric acid solutions

    SciTech Connect

    Turanov, A.N.

    1988-11-20

    Petroleum sulfoxides (PSO) are effective extractants for several metals. We discussed the distribution of petroleum sulfoxides and zirconium between aqueous solutions of hydrochloric and nitric acid and organic solvents, and also the macroporous sorbent impregnated with PSO. For the investigation we used a macroposous copolymer of styrene with divinylbenzene. Our investigation showed a noticeable decrease in the contamination of the raffinates by petroleum sulfoxides and their more complete utilization as extractant of metals from solutions of acids when PSO is deposited on a macroporous copolymer of styrene with divinylbenzene.

  6. Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?

    PubMed

    Markowitz, John S; Patrick, Kennerly S

    2008-06-01

    d,l-threo-methylphenidate (MPH) is an effective first-line treatment for the symptoms associated with attention-deficit/hyperactivity disorder. threo-methylphenidate inhibits the dopamine transporter and the norepinephrine transporter, resulting in elevations of these monoamines after impulse release. Although MPH has long been administered as a racemic mixture of the 2 enantiomers, d-MPH and l-MPH, converging lines of evidence drawn from investigations using in vitro systems, animal models, and humans indicate that it is predominantly, if not exclusively, d-MPH that mediates the pharmacological/therapeutic actions of MPH. In both rodent and primate animal models, the binding of radiolabeled d-MPH to dopamine transporter was found to be selective, saturable, and reversible, whereas binding of l-MPH was diffuse and nonspecific. The behavioral effects of the enantiomers of MPH have been tested in several animal models, and results indicate these observed behavioral changes are likewise mediated by d-MPH, whereas l-MPH has little or no effect.The contribution of the l-isomer to the overall pharmacological profile of the racemate remains unclear, owing to several studies suggesting that l-MPH may not be merely an inert isomeric ballast. For example, behavioral studies conducted in rats demonstrate an attenuation of the effect of d-MPH in animals pretreated with l-MPH, suggesting that l-MPH may interfere with the action of the active enantiomer. The importance of MPH chirality to central nervous system MPH receptor targeting has culminated in human imaging studies revealing that d-MPH binds specifically to striatal structures, whereas l-MPH binding is nonspecific. Taken together, data from in vitro, animal, and human studies support the premise that the d-enantiomer of MPH mediates the neurophysiological actions of MPH and therefore likely mediates its clinical efficacy.

  7. Can enantiomers be separated in achiral chromatographic systems?

    NASA Astrophysics Data System (ADS)

    Davankov, V. A.

    2016-10-01

    Consideration of chromatography of a nonracemic mixture on an achiral sorbent from a stereochemical point of view allows the claim that partial separation of the excess enantiomer zone from the racemate zone is possible only with analytes capable of self-associating under the conditions of the chromatographic column. It is from these positions that features of this process can be explained and conditions for its maximal proceeding formulated.

  8. On the asymmetric adsorption of phenylalanine enantiomers by kaolin.

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Flores, J.

    1973-01-01

    The attempt is described to verify a recent report that kaolin adsorbs D- and L-phenylalanine enantiomers to different extents from aqueous solutions at both pH 5.8 and pH 2. No evidence whatsoever could be found for the differential adsorption of D- versus L-phenylalanine by kaolin from either pH 6 or pH 2 solutions.

  9. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy

    NASA Astrophysics Data System (ADS)

    Shubert, V. Alvin; Schmitz, David; Medcraft, Chris; Patterson, David; Doyle, John M.; Schnell, Melanie

    2014-06-01

    In nature and as products of chemical syntheses, chiral molecules often exist in mixtures with other chiral molecules. The analysis of these complex mixtures to identify the components, determine which enantiomers are present, and to measure the enantiomeric excesses (ee) is still one of the challenging but very important tasks of analytical chemistry. These analyses are required at every step of modern drug development, from candidate searches to production and regulation. We present here a new method of identifying individual enantiomers in mixtures of chiral molecules in the gas phase. It is based on broadband rotational spectroscopy and employs a sum or difference frequency generation three-wave mixing process that involves a closed cycle of three rotational transitions. The phase of the acquired signal bares the signature of the enantiomer (see figure), as it depends upon the combined quantity, μaμbμc, which is of opposite sign between members of an enantiomeric pair. Furthermore, because the signal amplitude is proportional to the ee, this technique allows for both determining which enantiomer is in excess and by how much. The high resolution of our technique allows us to perform molecule specific measurements of mixtures of chiral molecules with μaμbμc ≠ 0, even when the molecules are very similar (e.g. conformational isomers). We introduce the technique and present results on the analysis of mixtures of the terpenes, carvone, menthone, and carvomenthenol. D. Patterson, M. Schnell, J. M. Doyle, Nature. 497, 475-477, 2013 V. A. Shubert, D. Schmitz, D. Patterson, J. M. Doyle, M. Schnell, Ang. Chem. Int. Ed. 53, 1152-1155,2014

  10. Chemoenzymatic synthesis of both enantiomers of alpha-tocotrienol.

    PubMed

    Chênevert, Robert; Courchesne, Gabriel; Pelchat, Nicholas

    2006-08-01

    The stereoselective acylation of the achiral chromanedimethanol derivative 1 by vinyl acetate in the presence of Candida antarctica lipase B gave the (S)-monoester 2 in high enantiomeric purity (ee > or = 98%). Enzymatic hydrolysis of diesters of compound 1 failed to give (R)-monoester 2 in good yield and high ee. Thus, both enantiomers of alpha-tocotrienol were synthesized from the (S)-monoester 2.

  11. Utilization of Alternate Chirality Enantiomers in Microbial Communities

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2010-01-01

    Our previous study of chirality led to interesting findings for some anaerobic extremophiles: the ability to metabolize substrates with alternate chirality enantiomers of amino acids and sugars. We have subsequently found that not just separate microbial species or strains but entire microbial communities have this ability. The functional division within a microbial community on proteo- and sugarlytic links was also reflected in a microbial diet with L-sugars and D-amino acids. Several questions are addressed in this paper. Why and when was this feature developed in a microbial world? Was it a secondary de novo adaptation in a bacterial world? Or is this a piece of genetic information that has been left in modern genomes as an atavism? Is it limited exclusively to prokaryotes, or does this ability also occur in eukaryotes? In this article, we have used a broader approach to study this phenomenon using anaerobic extremophilic strains from our laboratory collection. A series of experiments were performed on physiologically different groups of extremophilic anaerobes (pure and enrichment cultures). The following characteristics were studied: 1) the ability to grow on alternate chirality enantiomers -- L-sugars and D- amino acids; 2) Growth-inhibitory effect of alternate chirality enantiomers; 3) Stickland reaction with alternate chirality amino acids. The results of this research are presented in this paper.

  12. Toxicity and bioaccumulation of ethofumesate enantiomers in earthworm Eisenia fetida.

    PubMed

    Xu, Peng; Wang, Yinghuan; Zhang, Yanfeng; Li, Jianzhong; Wang, Huili

    2014-10-01

    Earthworms represent an important food source for many vertebrates and as a result, predators may encounter toxic effects via the food chain from consumption of contaminated worms. Therefore, including an assessment of xenobiotic to worms in risk assessment procedures is advisable. Here we studied the acute toxicity, bioaccumulation and elimination of ethofumesate enantiomers in earthworm, Eisenia fetida, in a soil. A slight difference in toxicity to earthworm between two enantiomers was found, and the calculated LC50 values for (+)-, rac- and (-)-ethofumesate were 4.51, 5.93 and 7.98 μg/cm(2), respectively, indicating that the acute toxicity of ethofumesate enantiomers was enantioselective. Earthworm can uptake ethofumesate but the bioaccumulation curve did not reach the steady state. In the elimination experiment, the concentrations of ethofumesate in earthworm declined following a first-order decay model with a short half life of 1.8d. The bioaccumulation and elimination of ethofumesate in earthworm were both nonenantioselective. In combination with other studies, a linear relationship between Log BSAFs and Log Kow was observed, and the Log BSAFs increased with increasing Log Kow. But the elimination rate did not show any correlation with the Kow value.

  13. Solubility properties of racemic praziquantel and its enantiomers.

    PubMed

    el-Arini, S K; Giron, D; Leuenberger, H

    1998-11-01

    The purpose of this study was to characterize the solubility and thermodynamic properties of the optical isomers of the anti-schistosomal drug, praziquantel (PZQ) and to compare these properties to those of the racemic product used in commercial preparations (Biltricide, generic drugs). The crystalline enantiomers of PZQ exhibited different thermal properties than the racemic drug. The melting points and the enthalpies of fusion obtained from the differential scanning calorimetry (DSC) scans were nearly identical between the isomers and were substantially lower than those of racemic PZQ [(+/-)-PZQ]. The DSC results indicate that (+/-)-PZQ is a racemic compound and not a racemic mixture. This was confirmed by powder x-ray diffraction analysis and the IR spectra. The 30 degrees decrease in the melting point was reflected in increased solubility of the enantiomers, which amounted to twice that of the racemic PZQ. The behavior of the isomers in the presence of beta-cyclodextrin (beta-CD) was studied in water at 37 degrees C. The solubility data (phase solubility diagrams) were linear for up to the highest concentration of added beta-CD investigated. The apparent stability constants determined from the phase solubility diagrams showed that both the (+) and (-) enantiomers as well as (+/-)-PZQ exhibited moderate affinity to form a 1:1 complex in solution with beta-CD. The findings of this study may be of importance when efforts are considered to improve pharmaceutical formulation of this anti-schistosomal drug.

  14. Liquid-vapor equilibrium in the systems hexane-benzene-petroleum sulfoxides-diethylene glycol and hexane-benzene-petroleum sulfoxides-dimethylformamide

    SciTech Connect

    Vakhitova, N.G.; Baikova, A.Y.; Murinov, Y.I.; Nikitin, Y.E.

    1985-12-01

    This paper reports the results of studies of liquid-vapor equilibrium in the benzene-hexane system in presence of binary extractants: petroleum sulfoxide-dimethylformamide (DMFA) and petroleum sulfoxide-diethylene glycol (DEG). The physicochemical properties of the extractants are presented and the influence of the content of slelective solvent on vapor-liquid equilibrium was studied; the total concentration of the binary solvent in the experiments was 50 vol. %. Results also show that the introduction of a second solvent into petroleum sulfoxides alters the vapor-liquid equilibrium in the system substantially. The volatility of hexane is increased considerably, especially in the case of the PSO-DMFA mixed extractant. In the case of benzene, petroleum sulfoxides and their mixtures with diethylene glycol and dimethylformamide are approximately equal in effectiveness in the region of low benzene concentrations. In the region of high benzene concentrations mixed extractants are more effective than petroleum sulfoxides; this is decisive for isolation of aromatic hydrocarbons from mixtures rich in aromatics.

  15. Dimethyl sulfoxide elevates hydrogen peroxide-mediated cell death in Saccharomyces cerevisiae by inhibiting the antioxidant function of methionine sulfoxide reductase A.

    PubMed

    Kwak, Geun-Hee; Choi, Seung Hee; Kim, Hwa-Young

    2010-09-01

    Dimethyl sulfoxide (DMSO) can be reduced to dimethyl sulfide by MsrA, which stereospecifically catalyzes the reduction of methionine-S-sulfoxide to methionine. Our previous study showed that DMSO can competitively inhibit methionine sulfoxide reduction ability of yeast and mammalian MsrA in both in vitro and in vivo, and also act as a non-competitive inhibitor for mammalian MsrB2, specific for the reduction of methionine-R-sulfoxide, with lower inhibition effects. The present study investigated the effects of DMSO on the physiological antioxidant functions of methionine sulfoxide reductases. DMSO elevated hydrogen peroxide-mediated Saccharomyces cerevisiae cell death, whereas it protected human SK-Hep1 cells against oxidative stress. DMSO reduced the protein-carbonyl content in yeast cells in normal conditions, but markedly increased protein-carbonyl accumulation under oxidative stress. Using Msr deletion mutant yeast cells, we demonstrated the DMSO's selective inhibition of the antioxidant function of MsrA in S. cerevisiae, resulting in an increase in oxidative stress-induced cytotoxicity.

  16. A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.

    PubMed Central

    Belizario, V. Y.; Amarillo, M. E.; de Leon, W. U.; de los Reyes, A. E.; Bugayong, M. G.; Macatangay, B. J. C.

    2003-01-01

    OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems. PMID:12640474

  17. In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents.

    PubMed

    Cedillo-Rivera, R; Muñoz, O

    1992-09-01

    The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5-nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5-nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated.

  18. Comparison of albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model.

    PubMed Central

    Taylor, D H; Morris, D L; Reffin, D; Richards, K S

    1989-01-01

    The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01). Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:2583567

  19. Recurrent toxocariasis due to chronic urticaria and successful treatment with prolonged albendazole therapy.

    PubMed

    Karagöz, Ergenekon; Selek, Mehmet Burak; Aydın, Ersin; Hatipoğlu, Mustafa; Turhan, Vedat; Acar, Ali; Öncül, Oral; Görenek, Levent

    2015-03-01

    Toxocariasis is a worldwide human helminthiasis, especially seen in temperate and tropical climate regions around the world. The diagnosis of this disease is performed on the basis of clinical symptoms and laboratory findings. Albendazole is one of the treatment choices for toxocariasis, with a currently recommended regimen of 10 mg/kg/day in two doses (400 mg twice daily) for 5 days. However, there is no precise consensus about the duration of the treatment. In this article, we report a case of toxocariasis; the patient visited our infectious disease polyclinic with complaints of long-term itching and urticarial skin lesions that were resistant to routine treatment and that recurred. Then, recurrent disease was resolved and skin lesions were diminished after prolonged albendazole therapy.

  20. Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A

    DTIC Science & Technology

    2011-03-01

    of Betti Reaction Product Enantiomers : Absolute Configuration and Inhibition of Botulinum Neurotoxin A John H. Cardellina II,† Rebecca C. Vieira...observing sufficient resolution of the two enantiomers on a Chiralcel OD column to permit semipreparative purification of adequate quantities of (þ)-1...comparison of the botulinum neurotoxin serotype A (BoNT/A) inhibitory activity of the (þ) and () enantiomers of 1 was accomplished via an HPLC-based assay

  1. Evaluating Effect of Albendazole on Trichuris trichiura Infection: A Systematic Review Article

    PubMed Central

    AHMADI JOUYBARI, Toraj; NAJAF GHOBADI, Khadije; LOTFI, Bahare; ALAVI MAJD, Hamid; AHMADI, Nayeb Ali; ROSTAMI-NEJAD, Mohammad; AGHAEI, Abbas

    2016-01-01

    Background: The aim of the study was assessment of defaults and conducted meta-analysis of the efficacy of single-dose oral albendazole against T. trichiura infection. Methods: We searched PubMed, ISI Web of Science, Science Direct, the Cochrane Central Register of Controlled Trials, and WHO library databases between 1983 and 2014. Data from 13 clinical trial articles were used. Each article was included the effect of single oral dose (400 mg) albendazole and placebo in treating two groups of patients with T. trichiura infection. For both groups in each article, sample size, the number of those with T. trichiura infection, and the number of those recovered following the intake of albendazole were identified and recorded. The relative risk and variance were computed. Funnel plot, Beggs and Eggers tests were used for assessment of publication bias. The random effect variance shift outlier model and likelihood ratio test were applied for detecting outliers. In order to detect influence, DFFITS values, Cook’s distances and COVRATIO were used. Data were analyzed using STATA and R software Results: The article number 13 and 9 were outlier and influence, respectively. Outlier is diagnosed by variance shift of target study in inferential method and by RR value in graphical method. Funnel plot and Beggs test did not show the publication bias (P=0.272). However, the Eggers test confirmed it (P=0.034). Meta-analysis after removal of article 13 showed that relative risk was 1.99 (CI 95% 1.71 – 2.31). Conclusion: The estimated RR and our meta-analyses show that treatment of T. trichiura with single oral doses of albendazole is unsatisfactory. New anthelminthics are urgently needed. PMID:28127355

  2. Selective oxidation of glycosyl sulfides to sulfoxides using magnesium monoperoxyphthalate and microwave irradiation.

    PubMed

    Chen, Ming-Yi; Patkar, Laxmikant Narhari; Lin, Chun-Cheng

    2004-04-16

    A protocol that uses moist magnesium monoperoxyphthalate (MMPP) as an oxidant under microwave irradiation rapidly yields a variety of glycosyl sulfoxides from corresponding sulfides in high yields with high selectivity.

  3. Does dimethyl sulfoxide increase protein immunomarking efficiency for dispersal and predation studies?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marking biological control agents facilitates studies of dispersal and predation. This study examines the effect of a biological solvent, dimethyl sulfoxide (DMSO), on retention of immunoglobulin G (IgG) protein solutions applied to Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae) eit...

  4. In vivo albendazole treatment of Taenia crassiceps cysticerci strain WFU: proliferation, damage, and recovery.

    PubMed

    Zurabian, R; Aguilar-Vega, L; Terrones Vargas, E; Cervera Hernández, M E; Willms, K; Ruíz-Velasco Acosta, S

    2013-11-01

    Taenia crassiceps has been widely experimented as a model for in vitro and in vivo studies on drug responses. The purpose of this study was to treat BALB/c mice infected with T. crassiceps strain WFU with commercially available albendazole and to analyze the reduction in parasite infrapopulations. Here, we describe the reduction and apparent damage of T. crassicceps WFU cysticerci in infected mice after antihelminthic drug treatment and subsequent inoculation of those treated parasites into a naïve host. We were able to reduce significantly the parasite counts to 33 and 48% after albendazole treatment for 20 or 25 days and compared with the untreated mice. We also observed morphological damage such as the partial blebbing in the tegument and parenchyma of treated parasites, as well as disorganized musculature and the loss of cell membranes in subtegumental tissue section. However, larvae from albendazole-treated mice inoculated into the next host were able to become re-established in the next murine host due, probably, to the survival of proliferative parasite cells.

  5. Stereochemistry of 10-sulfoxidation catalyzed by a soluble delta9 desaturase

    SciTech Connect

    Tremblay, A.E.; Shanklin, J.; Tan, N.; Whittle, E.; Hodgson, D. J.; Dawson, B.; Buist, P. H.

    2010-03-21

    The stereochemistry of castor stearoyl-ACP 9 desaturase-mediated 10-sulfoxidation has been determined. This was accomplished by 19F NMR analysis of a fluorine-tagged product, 18-fluoro-10-thiastearoyl ACP S-oxide, in combination with a chiral solvating agent, (R)-AMA. Sulfoxidation proceeds with the same stereoselectivity as hydrogen removal from the parent stearoyl substrate. These data validate the use of thia probes to determine the stereochemistry and cryptoregiochemistry of desaturase-mediated oxidations.

  6. Stereospecific micellar electrokinetic chromatography assay of methionine sulfoxide reductase activity employing a multiple layer coated capillary.

    PubMed

    Zhu, Qingfu; El-Mergawy, Rabab G; Heinemann, Stefan H; Schönherr, Roland; Jáč, Pavel; Scriba, Gerhard K E

    2013-09-01

    A micellar electrokinetic chromatography method for the analysis of the l-methionine sulfoxide diastereomers employing a successive multiple ionic-polymer layer coated fused-silica capillary was developed and validated in order to investigate the stereospecificity of methionine sulfoxide reductases. The capillary coating consisted of a first layer of hexadimethrine and a second layer of dextran sulfate providing a stable strong cathodic EOF and consequently highly repeatable analyte migration times. The methionine sulfoxide diastereomers, methionine as product as well as β-alanine as internal standard were derivatized by dabsyl chloride and separated using a 35 mM sodium phosphate buffer, pH 8.0, containing 25 mM SDS as BGE and a separation voltage of 25 kV. The method was validated in the range of 0.15-2.0 mM with respect to linearity and precision. The LODs of the analytes ranged between 0.04 and 0.10 mM. The assay was subsequently applied to determine the stereospecificity of methionine sulfoxide reductases as well as the enzyme kinetics of human methionine sulfoxide reductase A. Monitoring the decrease of the l-methionine-(S)-sulfoxide Km = 411.8 ± 33.8 μM and Vmax = 307.5 ± 10.8 μM/min were determined.

  7. Role of Helicobacter pylori methionine sulfoxide reductase in urease maturation

    PubMed Central

    Kuhns, Lisa G.; Mahawar, Manish; Sharp, Joshua S.; Benoit, Stéphane; Maier, Robert J.

    2014-01-01

    The persistence of the gastric pathogen Helicobacter pylori is due in part to urease and Msr (methionine sulfoxide reductase). Upon exposure to relatively mild (21% partial pressure of O2) oxidative stress, a Δmsr mutant showed both decreased urease specific activity in cell-free extracts and decreased nickel associated with the partially purified urease fraction as compared with the parent strain, yet urease apoprotein levels were the same for the Δmsr and wild-type extracts. Urease activity of the Δmsr mutant was not significantly different from the wild-type upon non-stress microaerobic incubation of strains. Urease maturation occurs through nickel mobilization via a suite of known accessory proteins, one being the GTPase UreG. Treatment of UreG with H2O2 resulted in oxidation of MS-identified methionine residues and loss of up to 70% of its GTPase activity. Incubation of pure H2O2-treated UreG with Msr led to reductive repair of nine methionine residues and recovery of up to full enzyme activity. Binding of Msr to both oxidized and non-oxidized UreG was observed by cross-linking. Therefore we conclude Msr aids the survival of H. pylori in part by ensuring continual UreG-mediated urease maturation under stress conditions. PMID:23181726

  8. Chemical Instability of Dimethyl Sulfoxide in Lithium-Air Batteries.

    PubMed

    Kwabi, David G; Batcho, Thomas P; Amanchukwu, Chibueze V; Ortiz-Vitoriano, Nagore; Hammond, Paula; Thompson, Carl V; Shao-Horn, Yang

    2014-08-21

    Although dimethyl sulfoxide (DMSO) has emerged as a promising solvent for Li-air batteries, enabling reversible oxygen reduction and evolution (2Li + O2 ⇔ Li2O2), DMSO is well known to react with superoxide-like species, which are intermediates in the Li-O2 reaction, and LiOH has been detected upon discharge in addition to Li2O2. Here we show that toroidal Li2O2 particles formed upon discharge gradually convert into flake-like LiOH particles upon prolonged exposure to a DMSO-based electrolyte, and the amount of LiOH detectable increases with increasing rest time in the electrolyte. Such time-dependent electrode changes upon and after discharge are not typically monitored and can explain vastly different amounts of Li2O2 and LiOH reported in oxygen cathodes discharged in DMSO-based electrolytes. The formation of LiOH is attributable to the chemical reactivity of DMSO with Li2O2 and superoxide-like species, which is supported by our findings that commercial Li2O2 powder can decompose DMSO to DMSO2, and that the presence of KO2 accelerates both DMSO decomposition and conversion of Li2O2 into LiOH.

  9. Dimethyl sulfoxide induces oxidative stress in the yeast Saccharomyces cerevisiae.

    PubMed

    Sadowska-Bartosz, Izabela; Pączka, Aleksandra; Mołoń, Mateusz; Bartosz, Grzegorz

    2013-12-01

    Dimethyl sulfoxide (DMSO) is used as a cryoprotectant for the preservation of cells, including yeast, and as a solvent for chemical compounds. We report that DMSO induces oxidative stress in the yeast. Saccharomyces cerevisiae wt strain EG-103 and its mutants Δsod1, Δsod2, and Δsod1 Δsod2 were used. Yeast were subjected to the action of 1-14% DMSO for 1 h at 28 °C. DMSO induced a concentration-dependent inhibition of yeast growth, the effect being more pronounced for mutants devoid of SOD (especially Δsod1 Δsod2). Cell viability was compromised. DMSO-concentration-dependent activity loss of succinate dehydrogenase, a FeS enzyme sensitive to oxidative stress, was observed. DMSO enhanced formation of reactive oxygen species, estimated with dihydroethidine in a concentration-dependent manner, the effect being again more pronounced in mutants devoid of superoxide dismutases. The content of cellular glutathione was increased with increasing DMSO concentrations, which may represent a compensatory response. Membrane fluidity, estimated by fluorescence polarization of DPH, was decreased by DMSO. These results demonstrate that DMSO, although generally considered to be antioxidant, induces oxidative stress in yeast cells.

  10. Diapause prevention effect of Bombyx mori by dimethyl sulfoxide.

    PubMed

    Yamamoto, Takayuki; Mase, Keisuke; Sawada, Hiroshi

    2013-01-01

    HCl treatment has been, for about 80 years, the primary method for the prevention of entry into embryonic diapauses of Bombyx mori. This is because no method is as effective as the HCl treatment. In this study, we discovered that dimethyl sulfoxide (DMSO) prevented entry into the diapause of the silkworm, Bombyx mori. The effect of diapause prevention was 78% as a result of treatment with 100% DMSO concentration, and the effect was comparable to that of the HCl treatment. In contrast, in the case of non-diapause eggs, hatchability was decreased by DMSO in a concentration-dependent manner. The effect of DMSO was restricted within 24 hours after oviposition of diapause eggs, and the critical period was slightly shorter than the effective period of the HCl treatment. DMSO analogs, such as dimethyl formamide (DMF) and dimethyl sulfide (DMS), did little preventive effect against the diapause. Furthermore, we also investigated the permeation effects of chemical compounds by DMSO. When treated with an inhibitor of protein kinase CK2 (CK2) dissolved in DMSO, the prevention rate of the diapause was less than 40%. This means that the inhibition effect by the CK2 inhibitor was the inhibition of embryonic development after diapause prevention by DMSO. These data suggest that DMSO has the effects of preventing from entering into the diapause and permeation of chemicals into diapause eggs.

  11. Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation.

    PubMed

    Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B; Baillargeon, Joanie; Hébert, Sébastien S; Planel, Emmanuel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro.

  12. Disposition of mepivacaine and bupivacaine enantiomers in sheep.

    PubMed

    Mather, L E

    1991-09-01

    Mepivacaine and bupivacaine are used clinically as racemic mixtures of enantiomers. In these studies the enantiomers of each agent were administered separately to sheep by i.v. bolus injection on separate occasions. Enantioselective disposition was deemed if the R:S ratio of the relevant pharmacokinetic parameter differed significantly from unity. Both enantiomers of both agents were cleared principally by the liver; urinary excretion of unmetabolized agents accounted for less than 2% of the doses. For R(-)-and S(+)-mepivacaine, respective mean (SEM) values of parameters were: total body clearance 1.20 (0.29) litre min-1 and 0.97 (0.20) litre min-1 (ns); total volume of distribution 144 (39) litre and 80 (21) litre (P less than 0.05); slow half-life 120 (40) min and 84 (22) min (ns); mean hepatic extraction ratio 0.50 (0.14) and 0.52 (0.09) (ns); mean hepatic clearance 0.75 (0.23) litre min-1 and 0.75 (0.18) litre min-1 (ns). For R(+)- and S(-)-bupivacaine, respective values were: total body clearance 0.77 (0.33) litre min-1 and 0.53 (0.26) litre min-1 (P less than 0.05); total volume of distribution 40 (10) litre and 43 (10) litre (ns); slow half-life 57 (10) min and 104 (21) min (P less than 0.05); mean hepatic extraction ratio 0.46 (0.15) and 0.29 (0.13) (P less than 0.05); mean hepatic clearance 0.85 (0.31) litre min-1 and 0.54 (0.26) litre min-1 (P less than 0.05). Thus there was enantioselective distribution of mepivacaine and enantioselective clearance of bupivacaine, but the magnitude of the effect was relatively small.

  13. Synthesis of L-enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides.

    PubMed

    Satoh, H; Yoshimura, Y; Sakata, S; Miura, S; Machida, H; Matsuda, A

    1998-05-05

    L-Enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides were synthesized from D-xylose. Methyl 2,3,5-tri-O-benzyl-D-xylofuranoside 6 was converted to the corresponding xylitol 7, which was treated with MsCl and then Na2S to give 1,4-anhydro-L-4-thioarabitol 8. As previously reported, Pummerer rearrangement of 8 followed by glycosylation with a silylated thymine and N4-acetylcytosine derivative and deprotection gave the corresponding alpha- and beta-L-4'-thioarabinofuranosyl pyrimidine nucleosides.

  14. Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

    PubMed

    Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

    2015-09-11

    Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

  15. Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding

    PubMed Central

    Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

    2015-01-01

    Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (−)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite “supersensitivity” to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 108-fold differential sensitivity of ΔD mice to (−)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >1010-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (−)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This “enantiomer odour discrimination paradox” indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification. PMID:26361056

  16. Differentiations of Enantiomers via Their Diasteriomeric Association Complexes--There Are Two Ways of Shaking Hands

    ERIC Educational Resources Information Center

    Mannschreck, Albrecht; Kiesswetter, Roland

    2005-01-01

    The intermolecular interaction of one enantiomer with a chiral auxiliary molecule may differ from the interaction of the other enantiomer with the same auxiliary molecule, explained by the example of unequal handshakes. This methodology helps present a lecture to the students that emphasizes the basic similarity of the association-based…

  17. Determination of the relative toxicity of enantiomers with cell-based assays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is an important need to determine the relative biological effects of toxin enantiomers found in poisonous plants. Current estimations of plant toxicities are based on total toxin levels without considering stereochemistry. However, if the predominant enantiomer found in a plant is of a less ...

  18. Capillary electrophoresis to quantitate gossypol enantiomers in cottonseed and flower petals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gossypol occurs as a mixture of enantiomers in cotton plant tissues including seed and flower petals. The (-)-enantiomer is less toxic to non-ruminant animals. Efforts to breed cottonseed with a low percentage of (-)-gossypol requires the determination of the (+)- to (-)-gossypol ratio in seed and...

  19. Albendazole inhibits endothelial cell migration, tube formation, vasopermeability, VEGF receptor-2 expression and suppresses retinal neovascularization in ROP model of angiogenesis

    SciTech Connect

    Pourgholami, Mohammad H.; Khachigian, Levon M.; Fahmy, Roger G.; Badar, Samina; Wang, Lisa; Chu, Stephanie Wai Ling; Morris, David Lawson

    2010-07-09

    The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.

  20. Enantiomer labelling, a method for the quantitative analysis of amino acids.

    PubMed

    Frank, H; Nicholson, G J; Bayer, E

    1978-12-21

    Enantiomer labelling a method for the quntitative analysis of optically active natural compounds by gas chromatography, involves the use of the unnatural enantiomer as an internal standard. With Chirasil-Val, a chiral stationary phase that is thermally stable up to up to 240 degrees, the enantiomers of amino acids and a variety of other compounds can be separated and quantitated. Incomplete recovery from the sample, incomplete derivatization, hydrolysis and thermal decomposition of the derivative and shifting response factors can be compensated for by adding the unnatural enantiomer. The accuracy of amino acid analysis by enantiomer labelling is equal or superior to that of hitherto known methods. The procedure affords a complete analysis of peptides with respect to both amino acid composition and the optical purity of each amino acid.

  1. A consideration of the patentability of enantiomers in the pharmaceutical industry in the United States.

    PubMed

    Miller, Chris P; Ullrich, John W

    2008-06-01

    During the last thirty years, concern over stereoselectivity of drug action has drawn a great deal of interest within the pharmaceutical field due to an improved understanding of the pharmacology and pharmacokinetics of enantiomers. Developing single enantiomers versus racemates or introducing a single enantiomer following the development of the racemic mixture appears to be the new trend. The intellectual property status of single enantiomers from racemates may be unclear. Drug discoverers and patent attorneys must examine the examples of the past to establish an appropriate pathway towards the development and intellectual property protection of chiral drugs. The review will focus on the patenting of an enantiomer in view of the prior art disclosure for the racemic mixture.

  2. Determination of tolperisone enantiomers in plasma and their disposition in rats.

    PubMed

    Yokoyama, T; Fukuda, K; Mori, S; Ogawa, M; Nagasawa, K

    1992-01-01

    A stereoselective assay for the determination of tolperisone enantiomers in plasma by high performance liquid chromatography was developed. Calibration curves obtained for the enantiomers were linear over plasma concentrations of 0.1-3.0 micrograms/ml with a detection limit of 20 ng/ml. Following intravenous bolus administration of 10 mg/kg of racemic tolperisone to rats, stereoselective disposition of tolperisone enantiomers was observed, and plasma concentrations were significantly higher for l-tolperisone than for d-tolperisone at 5, 15 and 30 min after administration. When either enantiomer was administered alone to rats, both enantiomers were found in plasma, indicating that a mutual chiral inversion occurs in the body.

  3. The determination of botanical origin of honeys based on enantiomer distribution of chiral volatile organic compounds.

    PubMed

    Špánik, Ivan; Pažitná, Alexandra; Šiška, Peter; Szolcsányi, Peter

    2014-09-01

    The enantiomer ratios of chiral volatile organic compounds in rapeseed, chestnut, orange, acacia, sunflower and linden honeys were determined by multi-dimensional gas chromatography using solid phase microextraction (SPME) as a sample pre-treatment procedure. Linalool oxides, linalool and hotrienol were present at the highest concentration levels, while significantly lower amounts of α-terpineol, 4-terpineol and all isomers of lilac aldehydes were found in all studied samples. On the other hand, enantiomer distribution of some chiral organic compounds in honey depends on their botanical origin. The significant differences in enantiomer ratio of linalool were observed for rapeseed honey that allows us to distinguish this type of honey from the other ones. The enantiomer ratios of lilac aldehydes were useful for distinguishing of orange and acacia honey from other studied monofloral honeys. Similarly, different enantiomer ratio of 4-terpineol was found for sunflower honeys.

  4. Dimethyl sulfoxide modulation of diabetes onset in NOD mice.

    PubMed

    Klandorf, H; Chirra, A R; DeGruccio, A; Girman, D J

    1989-02-01

    Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.

  5. Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets.

    PubMed

    Slichter, Sherrill J; Jones, Melinh; Ransom, Janet; Gettinger, Irena; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Corson, Jill; Bolgiano, Doug

    2014-10-01

    A literature review was conducted to assess the efficacy and safety of dimethyl sulfoxide (DMSO) cryopreserved platelets for potential military use. In vivo DMSO cryopreserved platelet studies published between 1972 and June of 2013 were reviewed. Assessed were the methods of cryopreservation, posttransfusion platelet responses, prevention or control of bleeding, and adverse events. Using the Department of Defense's preferred 6% DMSO cryopreservation method with centrifugation to remove the DMSO plasma before freezing at -65°C and no postthaw wash, mean radiolabeled platelet recoveries in 32 normal subjects were 33% ± 10% (52% ± 12% of the same subject's fresh platelet recoveries), and survivals were 7.5 ± 1.2 days (89% ± 15% of fresh platelet survivals). Using a variety of methods to freeze autologous platelets from 178 normal subjects, mean radiolabeled platelet recoveries were consistently 39% ± 9%, and survivals, 7.4 ± 1.4 days. More than 3000 cryopreserved platelet transfusions were given to 1334 patients. There were 19 hematology/oncology patient studies, and, in 9, mean 1-hour corrected count increments were 11 100 ± 3600 (range, 5700-15 800) after cryopreserved autologous platelet transfusions. In 5 studies, bleeding times improved after transfusion; in 3, there was either no improvement or a variable response. In 4 studies, there was immediate cessation of bleeding after transfusion; in 3 studies, patients being supported only with cryopreserved platelets had no bleeding. In 1 cardiopulmonary bypass study, cryopreserved platelets resulted in significantly less bleeding vs standard platelets. In 3 trauma studies, cryopreserved platelets were hemostatically effective. No significant adverse events were reported in any study. In summary, cryopreserved platelets have platelet recoveries that are about half of fresh platelets, but survivals are only minimally reduced. The platelets appear hemostatically effective and have no significant adverse events.

  6. Luminescence of Lanthanide-Dimethyl Sulfoxide Compound Solutions

    SciTech Connect

    Yao, Mingzhen; Li, Yuebin; Hossu, Marius; Joly, Alan G.; Liu, Zhongxin; Liu, Zuli; Chen, Wei

    2011-08-04

    Dimethyl sulfoxide (DMSO) has the ability to penetrate living tissues without causing significant damage. Of foremost importance to our understanding of the possible functions of DMSO in biological systems is its ability to replace some of the water molecules associated with the cellular constituents, or to affect the structure of the omnipresent water. Luminescence probes have been widely used for biological studies such as labeling, imaging and detection. Luminescence probes formed in DMSO may find new applications. Here, luminescence compounds formed by refluxing lanthanide nitrates of Ce, La, Tb, Yb, Nd, Gd and Eu in DMSO are reported and their luminescence properties investigated. Based on their luminescence spectral properties, the compounds can be classified into four classes. For compounds-I with Yb, Ce, and La, the excitation and emission spectra are very broad and their excitation or emission peaks are shifted to longer wavelengths when the monitored emission or excitation wavelength is longer . For compounds-II with Gd and Nd, both the excitation and emission spectra are very broad but their emission wavelengths change little at different excitation wavelengths. For Tb-DMSO as compound-III, both the typical emissions from the f - f transitions of Tb3+ and a broad emission at 445 nm are observed. At low temperatures of reaction, the f - f emissions are dominant, while at high temperatures such as 180 oC of reaction, the broad emission at 445 nm is dominant. For compound-IV with Eu-DMSO compounds, the dominant emissions are from the f - f transitions of Eu3+ and only a weak broad emission is observed, which is likely from the d - f transition of Eu2+ rather than from the metal to ligand charge transfer states.

  7. Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction.

    PubMed

    Song, Young Mi; Song, Sun-Ok; Jung, Yong-Keun; Kang, Eun-Seok; Cha, Bong Soo; Lee, Hyun Chul; Lee, Byung-Wan

    2012-07-01

    Induction of autophagy is known not only to regulate cellular homeostasis but also to decrease triglyceride accumulation in hepatocytes. The aim of this study is to investigate whether DMSO (dimethyl sulfoxide) has a beneficial role in free fatty acid-induced hepatic fat accumulation. In HepG2 cells, treatment with 0.5 mM palmitate for six hours significantly increased lipid and triglyceride (TG) accumulation, assessed by Oil-red O staining and TG quantification assay. Treatment with 0.01% DMSO for 16 h statistically reduced palmitate-induced TG contents. Pretreatment of 10 mM 3-methyladenine (3MA) for 2 h restored hepatocellular lipid contents, which were attenuated by treatment with DMSO. DMSO increased LC3-II conversion and decreased SQSTM1/p62 expression in a time and dose-dependent manner. In addition, the number of autophagosomes and autolysosomes, as seen under an electron microscopy, as well as the percentage of RFP-LAMP1 colocalized with GFP-LC3 dots in cells transfected with both GFP-LC3 and RFP-LAMP1, as seen under a fluorescent microscopy, also increased in DMSO-treated HepG2 cells. DMSO also suppressed p-eIF2α/p-EIF2S1, ATF4, p-AKT1, p-MTOR and p-p70s6k/p-RPS6KB2 expression as assessed by western blotting. Knockdown of ATF4 expression using siRNA suppressed ATF4 expression and phosphorylation of AKT1, MTOR and RPS6KB2, but increased LC3-II conversion. DMSO reduced not only soluble but also insoluble mtHTT (mutant huntingtin aggregates) expressions, which were masked in the presence of autophagy inhibitor. DMSO, a kind of chemical chaperone, activated autophagy by suppressing ATF4 expression and might play a protective role in the development of fatty acid-induced hepatosteatosis.

  8. Probing the stereochemistry of successive sulfoxidation of the insecticide fenamiphos in soils.

    PubMed

    Cai, Xiyun; Xiong, Weina; Xia, Tingting; Chen, Jingwen

    2014-10-07

    Successive sulfoxidation is widely recognized as a general characteristic of the metabolism of chiral or prochiral thioethers, producing sulfoxides, and sulfones. However, information related to the stereochemistry of this process in soils is rare. In this study, the biotic transformation of the insecticide fenamiphos (a model thioether) was followed over two months in three soils, through separate incubations with fenamiphos parent, the sulfoxide intermediate (FSO), the sulfone intermediate (FSO2), and their respective stereoisomers. The results showed that the successive sulfoxidation involved oxidation of fenamiphos to FSO and subsequently to FSO2 as well as diastereomerization/enantiomerization of FSO, all of which were primarily biotic and stereoselective. The concomitant hydrolysis of fenamiphos, FSO, and FSO2 to phenols that occurred at lower rates was biotically favorable, but not stereoselective. The stereochemistry of this successive sulfoxidation transferred principally through two parallel systems, R(+)-fenamiphos → SRPR(+)-/SSPR(-)-FSO → R(+)-FSO2 and S(-)-fenamiphos → SRPS(+)-/SSPS(-)-FSO → S(-)-FSO2, between which unidirectional intersystem crossing occurred at FSO via isomeric conversions and created a system of S(-)-fenamiphos → SRPR(+)-/SSPR(-)-FSO → R(+)-FSO2. This pattern accounts for the enrichment of the intermediates SSPR(-)-/SSPS(-)-FSO and R(+)-FSO2 that are toxicologically close to the highly toxic S(-)-fenamiphos, associated with soil application of fenamiphos. Selective formation/depletion of these intermediate stereoisomers leads to dramatic variations in the ecotoxicological effects of the thioether insecticide.

  9. Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse sewage samples.

    PubMed

    Oertel, Reinhard; Schubert, Sara; Mühlbauer, Viktoria; Büttner, Bozena; Marx, Conrad; Kirch, Wilhelm

    2014-10-01

    In a research project on risk management of harmful substances in water cycles, clindamycin and 12 further antibiotics were determined in different sewage samples. In contrast to other antibiotics, an increase of the clindamycin concentration in the final effluent in comparison to the influent of the sewage treatment plant (STP) was observed. A back transformation from the main metabolite clindamycin sulfoxide to clindamycin during the denitrification process has been discussed. Therefore, the concentration of this metabolite was measured additionally. Clindamycin sulfoxide was stable in the STP and the assumption of back transformation of the metabolite to clindamycin was confuted. To explain the increasing clindamycin concentration in the STP, the ratio of clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry spells with concentrated samples and with long dwell time in the sewer system. A short hydraulic retention in waste water system and diluted samples in periods of extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin concentration. A plausible explanation of this behavior could be that clindamycin was adsorbed strongly to a component of the sewage during this long residence time and in the STP, clindamycin was released. In the common sample preparation in the lab, clindamycin was not released. Measurements of clindamycin and clindamycin sulfoxide in the influent and effluent of STP is advised for sewage monitoring.

  10. Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis

    PubMed Central

    Nakajima, Hideaki; Huang, Tong-Yi; Sun, Kai-Yu; Chen, Shu-Ling; Chen, Ke-Bing

    2016-01-01

    Background Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. PMID

  11. Comparative Performances of Flubendazole and Albendazole in Cystic Echinococcosis: Ex Vivo Activity, Plasma/Cyst Disposition, and Efficacy in Infected Mice ▿

    PubMed Central

    Ceballos, Laura; Elissondo, Celina; Sánchez Bruni, Sergio; Denegri, Guillermo; Lanusse, Carlos; Alvarez, Luis

    2011-01-01

    The need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg·h/ml) and cysts (AUC = 0.3 μg·h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences

  12. Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis trophozoites.

    PubMed

    Pérez-Rangel, Armando; Hernández, José Manuel; Castillo-Romero, Araceli; Yépez-Mulia, Lilián; Castillo, Rafael; Hernández-Luis, Francisco; Nogueda-Torres, Benjamín; Luna-Arias, Juan Pedro; Radilla, Gerardo; León-Avila, Gloria

    2013-09-01

    In the present study, we evaluated the effect of an albendazole (ABZ) derivative JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated the tubulin cytoskeleton by confocal microscopy, and we found that the characteristic staining was modified. The scanning electron microscopy images revealed extremely damaged trophozoites and cyst-like cells. The confocal images revealed that this drug triggered the expression of cyst wall protein 1 and encystation. We also found that at low doses, AL triggered the encystation process too.

  13. Structure of the hydrated and dimethyl sulfoxide solvated rubidium ions in solution.

    PubMed

    D'Angelo, Paola; Persson, Ingmar

    2004-05-31

    The structure of the hydrated and the dimethyl sulfoxide solvated rubidium ions in solution has been determined by means of large-angle X-ray scattering (LAXS) and extended X-ray absorption fine structure (EXAFS) studies. The models of the hydrated and dimethyl sulfoxide solvated rubidium ions fitting the experimental data best are square antiprisms with Rb-O bond distances of 2.98(2) and 2.98(3) A, respectively. The EXAFS data show a significant asymmetry in the Rb-O bond distance distribution with C(3) values of 0.0076 and 0.015 A(3), respectively. No second hydration sphere is observed around the hydrated rubidium ion. The dimethyl sulfoxide solvated rubidium ion displays a Rb-O-S bond angle of ca. 130 degrees, which is typical for a medium hard electron acceptor such as rubidium.

  14. Selective molecular oxygen oxidation of thioethers to sulfoxides catalyzed by Ce(IV)

    SciTech Connect

    Riley, D.P.; Smith, M.R.; Correa, P.E.

    1988-01-06

    The selective molecular oxygen conversion of thioethers to sulfoxides is catalyzed by ceric ammonium nitrate (CAN) with rate enhancements that are at least three orders of magnitude greater than the uncatalyzed autoxidation of thioethers. Mechanistic studies (including spectroscopic, labeling, uptake, mixed reactant, and autocatalysis studies) of this novel reaction reveal that both atoms of dioxygen are incorporated into product sulfoxide, that a novel oxygen-driven Ce(IV)Ce(III) redox cycle gives rise to the catalysis, and that molecular oxygen efficiently traps a sulfur-centered radial cation of the thioether (produced by Ce(IV) oxidation of thioether) to yield the oxygenated radical cation R/sub 2/S/sup +/OO/sup ./, which, it is proposed, reoxidizes Ce(III) to Ce(IV). The zwitterionic R/sub 2/S/sup +/OO/sup -/ intermediate (persulfoxide) reacts with thioether to yield two sulfoxide product molecules.

  15. Morphologic Effect of Dimethyl Sulfoxide on the Blood-Brain Barrier

    NASA Astrophysics Data System (ADS)

    Broadwell, Richard D.; Salcman, Michael; Kaplan, Richard S.

    1982-07-01

    Dimethyl sulfoxide (DMSO) opens the blood-brain barrier of mice to the enzymatic tracer horseradish peroxidase. A single injection of horseradish peroxidase in 10 to 15 percent DMSO into the tail vein along with 10 to 15 percent DMSO delivered intraperitoneally allowed horseradish peroxidase to fill the extracellular clefts throughout the brain within 2 hours. In the absence of DMSO, peroxidase failed to enter brain parenchyma except through the circumventricular organs. Opening of the blood-brain barrier by DMSO is reversible. Dimethyl sulfoxide stimulated the pinocytosis of horseradish peroxidase by the cerebral endothelium; the peroxidase was then directed to lysosomal dense bodies for degradation. Vesicular transport of horseradish peroxidase from the luminal to the abluminal wall of the endothelial cell was not observed. Dimethyl sulfoxide did not alter the morphology of endothelial cells or brain parenchyma.

  16. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    SciTech Connect

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D. , Hopital Beaujon, Clichy )

    1990-11-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of (1-{sup 14}C)palmitic acid but not that of (1-{sup 14}C)palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of (1-{sup 14}C)palmitic acid and markedly inhibited the beta oxidation of (1-{sup 14}C)octanoic acid and (1-{sup 14}C)butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of ({sup 14}C)CO{sub 2} from (1-{sup 14}C)fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids.

  17. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs.

    PubMed

    Jacques, Vincent; Czarnik, Anthony W; Judge, Thomas M; Van der Ploeg, Lex H T; DeWitt, Sheila H

    2015-03-24

    Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using "deuterium-enabled chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics.

  18. Phototransformation of carboxin in water. Toxicity of the pesticide and its sulfoxide to aquatic organisms.

    PubMed

    DellaGreca, Marina; Iesce, Maria Rosaria; Cermola, Flavio; Rubino, Maria; Isidori, Marina

    2004-10-06

    Sunlight exposure of aqueous suspensions of carboxin (1) causes its phototransformation to sulfoxide 2 and minor components. Similar effects are observed in the presence of humic acid or nitrate or at different pH values. Photoproducts 2-9 were isolated by chromatographic techniques and/or identified by spectroscopic means. Carboxin 1 and its main photoproduct sulfoxide 2 were tested to evaluate acute toxicity to primary consumers typical of the aquatic environment: the rotifer Brachionus calyciflorus and two crustaceans, Daphnia magna and Thamnocephalus platyurus. Chronic tests comprised a producer, the alga Pseudokirchneriella subcapitata, and a consumer, the crustacean Ceriodaphnia dubia.

  19. Enantiomer-Specific State Transfer of Chiral Molecules

    NASA Astrophysics Data System (ADS)

    Eibenberger, Sandra; Doyle, John; Patterson, David

    2017-03-01

    State-selective enantiomeric excess is realized using microwave-driven coherent population transfer. The method selectively promotes either R or S molecules to a higher rotational state by phase-controlled microwave pulses that drive electric-dipole allowed rotational transitions. We demonstrate the enantiomer-specific state transfer method using enantiopure samples of 1,2-propanediol. This method of state-specific enantiomeric enrichment can be applied to a large class of asymmetric, chiral molecules that can be vaporized and cooled to the point where rotationally resolved spectroscopy is possible, including molecules that rapidly racemize. The rapid chiral switching demonstrated here allows for new approaches in high-precision spectroscopic searches for parity violation in chiral molecules.

  20. Nano-liquid chromatography applied to enantiomers separation.

    PubMed

    Fanali, Salvatore

    2017-02-24

    This paper presents the state of the art concerning the separation of chiral compounds by means of nano-liquid chromatography (nano-LC). The enantiomers' separation and determination are a subject of fundamental importance in various application fields such as pharmaceutical industry, biomedicine, food, agrochemical etc. Nano-LC is a miniaturized chromatographic technique offering some advantages over conventional ones such as low consumption of mobile phase, sample volume and amount of chiral stationary phase, reduced costs etc. This is reported in the first part of the paper illustrating the features of the nano-LC. In addition, chiral resolution methods are briefly illustrated. Some chiral selectors, used in high-performance liquid chromatography have also been applied in nano-LC including cyclodextrins, glycopeptide antibiotics, modified polysaccharides etc. This is discussed in the second part of the review. Finally some examples of the applications available in literature are reported.

  1. Pharmacokinetics of venlafaxine enantiomers and their metabolites in psoriasis patients.

    PubMed

    Godoy, Ana Leonor Pardo Campos; Rocha, Adriana; da Silva Souza, Cacilda; Lanchote, Vera Lucia

    2016-05-01

    Psoriasis is a chronic inflammatory disease associated with several comorbidities, including depression. Previous studies have shown that inflammatory diseases downregulate the expression and suppress activity of CYP isoforms. Venlafaxine (VLX) is an antidepressant metabolized mainly by CYP2D6 to O-desmethylvenlafaxine (ODV), CYP3A to N-desmethylvenlafaxine (NDV), and CYP2D6 and CYP3A to N,O-didesmethylvenlafaxine (DDV). This study evaluated the influence of psoriasis on the enantioselective pharmacokinetics of VLX. Psoriasis patients (n = 13) and healthy volunteers (n = 11) phenotyped as CYP2D6 extensive (EM) or poor metabolizers (n = 1) received a single oral dose of 150 mg racemic VLX. Plasma concentrations of TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines were higher in EM psoriasis patients when compared with healthy volunteers. IL-6 plasma concentrations varied from 0.4 to 12.9 pg/mL (mean, 2.1 pg/mL) in healthy volunteers and from 0.4 to 29.3 pg/mL (mean, 4.2 pg/mL) in psoriatic patients. VLX pharmacokinetics are enantioselective in healthy volunteers and psoriasis patients phenotyped as EM. Higher AUC values for the (S)-VLX, (S)-NDV, and (S)-DDV enantiomers were observed in healthy volunteers, whereas higher AUC values for (S)-VLX and (R)-ODV were found in psoriasis patients phenotyped as EM. Psoriasis does not alter the pharmacokinetics of the VLX enantiomers probably because of the low levels of IL-6 plasma concentrations.

  2. Albumin's Influence on Carprofen Enantiomers-Hymecromone Interaction.

    PubMed

    Tang, Mingjie; Guo, Yanjie; Gao, Youshui; Tang, Chao; Dang, Xiaoqian; Zhou, Zubin; Sun, Yuqiang; Wang, Kunzheng

    2016-03-01

    Hymecromone is an important coumarin drug, and carprofen is one of the most important nonsteroidal antiinflammatory drugs (NSAIDs). The present study aims to determine the influence of bovine serum albumin (BSA) on the carprofen-hymecromone interaction. The inhibition of carprofen enantiomers on the UDP-glucuronosyltransferase (UGT) 2B7-catalyzed glucuronidation of hymecromone was investigated in the UGTs incubation system with and without BSA. The inhibition capability of increased by 20% (P < 0.001) of (R)-carprofen after the addition of 0.5% BSA in the incubation mixture. In contrast, no significant difference was observed for the inhibition of (S)-carprofen on UGT2B7 activity in the absence or presence of 0.5% BSA in the incubation system. The Lineweaver-Burk plot showed that the intersection point was located in the vertical axis, indicating the competitive inhibition of (R)-carprofen on UGT2B7 in the incubation system with BSA, which is consistent with the inhibition kinetic type of (R)-carprofen on UGT2B7 in the incubation system without BSA. Furthermore, the second plot using the slopes from the Lineweaver-Burk versus the concentrations of (R)-carprofen showed that the fitting equation was y=39.997x+50. Using this equation, the inhibition kinetic parameter was calculated to be 1.3 μM. For (S)-carprofen, the intersection point was located in the horizontal axis in the Lineweaver-Burk plot for the incubation system with BSA, indicating the noncompetitive inhibition of (S)-carprofen on the activity of UGT2B7. The fitting plot of the second plot was y=24.6x+180, and the inhibition kinetic parameter was 7.3 μM. In conclusion, the present study gives a short summary of BSA's influence on the carprofen enantiomers-hymecromone interaction, which will guide the clinical application of carprofen and hymecromone.

  3. [Escitalopram and citalopram: the unexpected role of the R-enantiomer].

    PubMed

    Jacquot, C; David, D J; Gardier, A M; Sánchez, C

    2007-01-01

    Citalopram, a selective serotonin reuptake inhibitor, is composed of 2 enantiomers, R-citalopram and S-citalopram, 2 different non-superimposable mirror image forms of the same molecule. Separating these 2 enantiomers has enabled studying their individual properties. Citalopram's pharmacologic activity is centered on the S enantiomer's high affinity for the serotonin transporter which is twice as high as citalopram's and 30 to 40 times higher than R-citalopram. This leads to an inhibition of serotonin reuptake two times higher for escitalopram compared with citalopram and confirms that citalopram's pharmacologic activity is due to the S-enantiomer. Contrary to what might be expected, the effect of escitalopram (DCI of S-citalopram) is not superimposable on an equivalent dose of citalopram but is superior. Several hypotheses could explain this superiority. First, conversions of the S-enantiomer into the R-enantiomer may occur, but there is no reason why this phenomenon would happen more when both enantiomers are present than when escitalopram is alone. Furthermore, pharmacokinetic studies have shown that S or R configurations are stable in vivo. Second, a particular action of R-citalopram may influence the S-enantiomer's kinetic from intestinal absorption to blood-brain barrier. But concentrations of both enantiomers in the frontal cortex are the same. Therefore, R-citalopram does not interfere with escitalopram's kinetic. Finally, interactions may appear at the synaptic level. Results of experimentation, after in situ injection to the cortex level, confirm that an interaction between the 2 enantiomers takes place at that level. A direct negative interaction of R-citalopram on one or several effectors that create the antidepressive effect seems justified. This negative interaction has been studied in depth. Animal models have shown that the R-enantiomer has no antidepressive potential and when associated with escitalopram prohedonic effects disappear. Escitalopram

  4. Persistent eosinophilia and Strongyloides infection in Montagnard refugees after presumptive albendazole therapy.

    PubMed

    Goswami, Neela D; Shah, J Jina; Corey, G Ralph; Stout, Jason E

    2009-08-01

    Chronic helminth infections are common in refugee populations and may persist years after immigration. Asymptomatic Strongyloides stercoralis infection raises particular concern because of its potential for complications in immunosuppressed patients. We examined 172 Montagnard refugees resettled to Wake County, North Carolina from 2002 through 2003. Refugees were pretreated with albendazole for five days and screened for health conditions after arrival. Eosinophilia was present in 41 of 171 refugees at the first blood draw. Only 1 of 172 had a stool helminth (Fasciola) identified by microscopy. On repeat testing, 13 people had persistent eosinophilia. Results of serologic analysis for Strongyloides were available in 24 persons. Eosinophil counts decreased significantly after treatment with ivermectin in nine refugees (P = 0.039). Persistent eosinophilia, likely caused by Strongyloides infection, was common in this cohort of Montagnard refugees. Clinicians should understand the limitations of stool microscopy in diagnosis of strongyloidiasis, the limited effectiveness of albendazole in treating strongyloidiasis, and the importance of following-up refugees with persistent eosinophilia.

  5. In vitro Effects of Albendazole on Raillietina echinobothrida, the Cestode of Chicken, Gallus domesticus

    PubMed Central

    Lalchhandama, K

    2010-01-01

    Albendazole, a member of benzimidazole group of compounds, has been shown to have a broad spectrum activity against all classes of helminth parasites. Although it has also been experimentally proven to be effective against cestode infection of poultry, the actual effects of the drug are not yet described. The present in vitro study demonstrated that the commercial prescription drug Zentel® was significantly effective against adult Raillietina echinobothrida Mégnin, the major cestode parasite of domestic chicken, Gallus domesticus Linnaeus. It clearly exhibited dose-dependent lethal activity at the different concentrations that were tested. Scanning electron microscopy (SEM) revealed that the drug caused extensive structural alterations on the body surface of the cestode. Severe contraction and shrinkage were evident throughout the entire length of the body. The suckers on the scolex became invaginated due to shrinkage. The distinct body segments, the proglottides, were completely distorted. The fine hairy microtriches on the tegument were obliterated and in its place were formed abnormal clumps of tissues. The results of this investigation are in favor of the use of albendazole as a drug of choice in the management of poultry helminthiasis. PMID:21264097

  6. The anthelmintic efficacy of albendazole against gastrointestinal roundworms, tapeworms, lungworms and liverflukes in sheep.

    PubMed

    van Schalkwyk, P C; Geyser, T L; Récio, M; Erasmus, F P

    1979-03-01

    Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica.

  7. Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole.

    PubMed

    Bundy, D A; Thompson, D E; Cooper, E S; Blanchard, J

    1985-01-01

    The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

  8. The CGC enantiomer separation of 2-arylcarboxylic acid esters by using β-cyclodextrin derivatives as chiral stationary phases.

    PubMed

    Shi, Xueyan; Liu, Feipeng; Mao, Jianyou

    2016-03-17

    Chiral 2-arylcarboxylic acid esters are important intermediates in preparation of enantioenriched 2-arylpropionic acids type Non-steroidal anti-inflammatory drugs (NSAIDs). Enantiomer separation of 2-arylcarboxylic acid esters is crucial for evaluation of the asymmetric synthesis efficiency and the enantiomer excess of chiral 2-arylcarboxylic acid derivatives. The capillary gas chromatography (CGC) enantiomer separation of 17 pairs of 2-arylcarboxylic acid esters enantiomers was conducted by using seven different β-cyclodextrin derivatives (CDs) as chiral stationary phases. It was found that for the 7 pairs of 2-phenylpropionates enantiomers, CDs with both alkyl and acyl substituents especially 2,6-di-O-pentyl-3-O-butyryl-β-cyclodextrin exhibited better enantiomer separation abilities than the other CDs examined. For the 7 pairs of 2-(4-substituted phenyl)propionates enantiomers, 2,3,6-tri-O-methyl-β-cyclodextrin possessed better enantiomer separation abilities than the other CDs. Among the 3 pairs of 2-phenylbutyrates enantiomers examined, only methyl 2-phenylbutyrate enantiomers could be separated by three CDs among the 7 CDs tested, while enantiomers of ethyl 2-phenylbutyrate and isopropyl 2-phenylbutyrate couldn't be separated by any of the 7 CDs tested. Besides the structures of CDs, the structures of 2-arylcarboxylic acid esters including different ester moieties, substituents of phenyl, and different carboxylic acids moieties in 2-arylcarboxylic acid esters also affected the enantiomer separation results greatly. The CGC enantiomer separation results of 2-arylcarboxylic acid esters on different CDs are useful for solving the enantiomer separation problem of 2-arylcarboxylic acid esters.

  9. Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?

    PubMed

    Romo, Matthew L; Carpio, Arturo; Kelvin, Elizabeth A

    2014-04-01

    Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized.

  10. A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis

    PubMed Central

    Solaymani-Mohammadi, Shahram; Genkinger, Jeanine M.; Loffredo, Christopher A.; Singer, Steven M.

    2010-01-01

    Background Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans. Methodology and Principal Findings We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion. Conclusions/Significance The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement

  11. Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

    PubMed

    Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

    2009-10-01

    A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

  12. Asymmetric synthesis of both the enantiomers of trans-3-hydroxypipecolic acid.

    PubMed

    Kumar, Pradeep; Bodas, Mandar S

    2005-01-07

    Both the enantiomers of trans-3-hydroxypipecolic acid have been synthesized employing the Sharpless asymmetric dihydroxylation and epoxidation as the key steps starting from a commercially available starting material 1,4-butanediol.

  13. Detection and discrimination of carvone enantiomers in rats with olfactory bulb lesions.

    PubMed

    Slotnick, B; Bisulco, S

    2003-01-01

    Rats with lesions of dorsal and dorsolateral bulbar sites known to be differentially responsive to carvone enantiomers were tested for their ability to detect (+)-carvone, to discriminate between (+)-carvone from (-)-carvone, and to discriminate (+)-carvone from mixtures of both enantiomers after they had been pre-trained or not pre-trained on these tasks prior to surgery. In postoperative tests, rats pre-trained on the enantiomer discrimination problems made somewhat fewer errors than those not pre-trained, but experimental rats performed as well as controls (those that had one intact olfactory bulb) within both conditions and on each task. These results indicate that removal of most bulbar sites known to be differentially responsive to carvone enantiomers and the consequent disruption of normal patterns of bulbar input produced in response to carvones are largely without effect on the ability of rats to discriminate between these odors.

  14. ANALYSIS OF THE ENANTIOMERS OF CHIRAL PESTICIDES AND OTHER POLLUTANTS IN ENVIRONMENTAL SAMPLES BY CAPILLARY ELECTROPHORESIS

    EPA Science Inventory

    The generic method described here involves typical capillary electrophoresis (CE) techniques, with the addition of cyclodextrin chiral selectors to the electrolyte for enantiomer separation and also, in the case of neutral analytes, the further addition of a micelle forming comp...

  15. Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.

    PubMed

    Dou, Xiaorui; Su, Xin; Wang, Yue; Chen, Yadong; Shen, Weiyang

    2015-11-01

    Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP.

  16. CAPILLARY ELECTROPHORESIS FOR ENANTIOMER SEPARATION AND MEASUREMENT OF ENANTIOSELECTIVITY OF CHIRAL POLLUTANTS IN THE ENVIRONMENT

    EPA Science Inventory

    Chiral pollutants exist as 2 species, -- enantiomers - that have identical physical and chemical properties except when they interact with enzymes or other chiral molecules; then they usually react selectively. This enantioselectivity results in different rates of microbial trans...

  17. Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites.

    PubMed

    Cooper, George; Rios, Andro C

    2016-06-14

    Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers.

  18. Capillary electrophoresis to quantitate gossypol enantiomers in cotton flower petals and seed.

    PubMed

    Vshivkov, Sergey; Pshenichnov, Egor; Golubenko, Zamira; Akhunov, Alik; Namazov, Shadman; Stipanovic, Robert D

    2012-11-01

    Gossypol is a toxic compound that occurs as a mixture of enantiomers in cotton plant tissues including seed and flower petals. The (-)-enantiomer is more toxic to non-ruminant animals. Efforts to breed cottonseed with a low percentage of (-)-gossypol requires determination of the (+)- to (-)-gossypol ratio in seed and flower petals. We report a method to quantitatively determine the total gossypol and percent of its enantiomers in cotton tissues using high performance capillary electrophoresis (HPCE). The method utilizes a borate buffer at pH 9.3 using a capillary with internal diameter of 50μm, effective length of 24.5cm, 15kV and cassette temperature of 15°C. This method provides high accuracy and reproducible results with a limit of detection of the individual enantiomers of less than 36ng/mL providing base line separation in less than 6min.

  19. HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC SEPARATION OF THE ENANTIOMERS OF ORGANOPHOSPHORUS PESTICIDES ON POLYSACCHARIDE CHIRAL STATIONARY PHASES

    EPA Science Inventory

    High-performance liquid chromatographic separation of the individual enantiomers of 12 organophosphorus pesticides (OPs) was obtained on polysaccharide enantioselective HPLC columns using alkane-alcohol mobile phase. The OP pesticides were crotoxyphos, dialifor, fonofos, fenamiph...

  20. HBCD stereoisomer pattern in mirror carps following dietary exposure to pure gamma-HBCD enantiomers.

    PubMed

    Esslinger, Susanne; Becker, Roland; Müller-Belecke, Andreas; Bremser, Wolfram; Jung, Christian; Nehls, Irene

    2010-09-08

    1,2,5,6,9,10-hexabromocyclododecane (HBCD) is a brominated flame retardant consisting of a mixture of diastereomeric pairs of enantiomers that is a known omnipresent, environmental contaminant. The present study investigated the possibility of bioisomerization of HBCD stereoisomers. Therefore, mirror carps (Cyprinus carpio morpha noblis) were exposed to pure (+)- and (-)-gamma-HBCD, randomly sampled biweekly over a period of three and a half months and the fillets were subjected to enantiomer-specific determination of HBCD. Considering the background contamination of the fish at the beginning of the feeding period, significant enrichment of the respectively fed gamma-enantiomer was already detectable after two weeks of exposure. However, no significant enrichment of the respectively expected alpha-enantiomer was observed within this period. Thus, no evidence for the isomerization of HBCD stereoisomers was found in mirror carp under the applied conditions.

  1. Distribution of enantiomers of volatile organic compounds in selected fruit distillates.

    PubMed

    Vyviurska, Olga; Zvrškovcová, Helena; Špánik, Ivan

    2017-01-01

    The enantiomer ratios of chiral volatile organic compounds in fruit distillates were determined by multidimensional gas chromatography using solid-phase microextraction (SPME) as a sample treatment procedure. Linalool and its oxides, limonene, α-terpineol, and nerolidol, were present at the highest concentration levels, while significantly lower amounts of β-citronellol and lactones were found in the studied samples. However, almost all terpenoids mainly occur as a racemic or near-racemic mixture; enantiomer distribution of some chiral organic compounds in fruit distillates correlated to a botanical origin. In particular, a significant enantiomeric excess of (R)-linalool and (S)-α-terpineol was found only for pear brandy, and likewise the dominance (R)-limonene and the second eluted enantiomer of nerolidol for Sorbus domestica and strawberry, respectively. The distribution of γ-lactones stereoisomers was more nonspecific, with a general excess of the R-enantiomer.

  2. Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development.

    PubMed

    Leek, Hanna; Andersson, Shalini

    2017-01-18

    The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates.

  3. Exploring the Use of a Guanine-Rich Catalytic DNA for Sulfoxide Preparation.

    PubMed

    Dellafiore, María A; Montserrat, Javier M; Iribarren, Adolfo M

    2015-01-01

    A guanine-rich DNA oligonucleotide complexed with hemin was used to catalyze controlled oxygen transfer reactions to different sulfides for sulfoxide preparation in the presence of H2O2. Comparable activities were obtained when using fully modified L-DNA. In addition, oligonucleotide immobilization led to an active catalyst which could be successfully recovered and reused without loss of activity.

  4. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  5. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  6. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  7. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  8. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  9. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  10. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  11. Organization of dimethyl sulfoxide reductase in the plasma membrane of Escherichia coli.

    PubMed Central

    Sambasivarao, D; Scraba, D G; Trieber, C; Weiner, J H

    1990-01-01

    Dimethyl sulfoxide reductase is a trimeric, membrane-bound, iron-sulfur molybdoenzyme induced in Escherichia coli under anaerobic growth conditions. The enzyme catalyzes the reduction of dimethyl sulfoxide, trimethylamine N-oxide, and a variety of S- and N-oxide compounds. The topology of dimethyl sulfoxide reductase subunits was probed by a combination of techniques. Immunoblot analysis of the periplasmic proteins from the osmotic shock and chloroform wash fluids indicated that the subunits were not free in the periplasm. The reductase was susceptible to proteases in everted membrane vesicles, but the enzyme in outer membrane-permeabilized cells became protease sensitive only after detergent solubilization of the E. coli plasma membrane. Lactoperoxidase catalyzed the iodination of each of the three subunits in an everted membrane vesicle preparation. Antibodies to dimethyl sulfoxide reductase and fumarate reductase specifically agglutinated the everted membrane vesicles. No TnphoA fusions could be found in the dmsA or -B genes, indicating that these subunits were not translocated to the periplasm. Immunogold electron microscopy of everted membrane vesicles and thin sections by using antibodies to the DmsABC, DmsA, DmsB subunits resulted in specific labeling of the cytoplasmic surface of the inner membrane. These results show that the DmsA (catalytic subunit) and DmsB (electron transfer subunit) are membrane-extrinsic subunits facing the cytoplasmic side of the plasma membrane. Images PMID:2170332

  12. Ruthenium(II) sulfoxide-maltolato and -nitroimidazole complexes: synthesis and MTT assay.

    PubMed

    Wu, Adam; Kennedy, David C; Patrick, Brian O; James, Brian R

    2003-11-17

    Ru(II) sulfoxide-maltolato complexes, Ru(ma)(2)(L)(2) (L = DMSO (1a) and TMSO (1b) or L(2) = BESE (1c)), were synthesized, as well as the analogous ethylmaltolato derivatives, Ru(etma)(2)(L)(2) (2a-c) (ma = 3-hydroxy-2-methylpyran-4-onate, etma = 2-ethyl-3-hydroxypyran-4-onate, TMSO = tetramethylene sulfoxide, BESE = 1,2-bis(ethylsulfinyl)ethane). A Ru(II) bidentate sulfoxide-metronidazole complex, RuCl(2)(BESE)(metro)(2) (3), was also synthesized (metro = metronidazole = 2-methyl-5-nitroimidazole-1-ethanol). The complexes were characterized generally by (1)H NMR, UV-vis, and IR spectroscopies, as well as MS, elemental analysis, solution conductivity, and cyclic voltammetry. The molecular structures of Ru(ma)(2)(S,R-BESE) (1c) and trans-RuCl(2)(R,R-BESE)(metro)(2) (3) were determined by X-ray crystallography. All sulfoxide ligands are S-bonded. The complexes were tested against human breast cancer cells (MDA-MB-435S) using an in vitro MTT assay, a colorimetric determination of cell viability: 2a,b exhibit the lowest IC(50) values of 190 +/- 10 and 220 +/- 10 microM, respectively. Cisplatin exhibits an IC(50) value of 30 +/- 5 microM.

  13. Unusual nickel-mediated C-S cleavage of alkyl and aryl sulfoxides.

    PubMed

    Schaub, Thomas; Backes, Marc; Radius, Udo

    2007-05-28

    The first examples of transition metal mediated C-S cleavage of sulfoxides containing sp2- and sp3-hybridized carbon bonds attached to the sulfur atom and the first example of a structurally characterized complex featuring an oxygen-bound sulfinyl ligand are presented.

  14. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a...-responsive lesions may be due to the presence of an infection which requires identification or...

  15. A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates-Bioinspired Sulfoxidation Catalysts.

    PubMed

    Tomanová, Petra; Šturala, Jiří; Buděšínský, Miloš; Cibulka, Radek

    2015-11-04

    A click chemistry approach based on the reaction between alkynylflavins and mono(6-azido-6-deoxy)-β-cyclodextrin has proven to be a useful tool for the synthesis of flavin-cyclodextrin conjugates studied as monooxygenase mimics in enantioselective sulfoxidations.

  16. Palladium-catalyzed decarboxylative ortho-arylation of 2-pyridyl sulfoxides with benzoyl peroxides.

    PubMed

    Sun, Meng; Wang, Zhe; Wang, Jiaxin; Guo, Peiyu; Chen, Xiangxiang; Li, Ya-Min

    2016-12-07

    A palladium catalyzed efficient strategy for regio-selective ortho-arylation of sulfoxides with benzoyl peroxides via decarboxylation has been developed. This reaction proceeds smoothly, tolerates a variety of functional groups, and provides easy access to the synthesis of different biaryl compounds.

  17. Comparative effects of medetomidine enantiomers on in vitro and in vivo microsomal drug metabolism.

    PubMed

    Pelkonen, O; Puurunen, J; Arvela, P; Lammintausta, R

    1991-09-01

    The effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, and its levo enantiomer (MPV-1441), on in vitro microsomal P450-dependent drug-metabolizing activities as well as on in vivo aminopyrine elimination and hexobarbital sleeping time were studied. Both enantiomers inhibited the oxidative metabolism of several model substrates and testosterone in rat liver microsomal incubations. Microsomal activities derived from control animals or rats pretreated with phenobarbital were more sensitive to inhibitory effects of dexmedetomidine than those from rats treated with 3-methylcholanthrene. Enzyme activities in human liver microsomes were also inhibited by dexmedetomidine. Retardation of the elimination of aminopyrine was dose-dependent; elimination was marginally retarded with doses up to 100 micrograms/kg (from 17 to 23 min.; both enantiomers). Higher doses of the levo enantiomer prolonged aminopyrine half-life to 78 (1 mg/kg) and 162 min. (10 mg/kg). The hexobarbital sleeping time was prolonged by the dose of 1 mg/kg of the levo enantiomer (128 min. versus 20 min. in controls), while the dose of 0.1 mg/kg had no effect (23 versus 20 min.). These studies indicate that both enantiomers of medetomidine are inhibitors of microsomal drug metabolism in vitro, but significant effects on aminopyrine elimination or hexobarbital sleeping time are apparent only at doses, which do not allow the use of dexmedetomidine because of excessive sedative effect.

  18. Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

    PubMed

    Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

    2006-07-01

    Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

  19. Study of the solubility of petroleum sulfoxides and their extraction from sulfate and fluoride-sulfate solutions

    SciTech Connect

    Nikolaev, A.I.; Zalkind, L.M.; Babkin, A.G.; Kasikova, N.I.; Toropov, Y.A.

    1983-02-20

    Study of the influence of the ammonium sulfate and sulfuric and hydrochloric acid concentrations and of temperature on the solubility of petroleum sulfoxides in aqueous solutions showed that the solubility of petroleum sulfoxides is in the range 0.1-2.1 g/liter. The solubility of petroleum sulfoxides under conditions of extraction of metals from fluoride-sulfate solutions was determined with the aid of factorial experimental design. The initial and constant solubilities of petroleum sulfoxides were determined. Washing of the sulfoxides with a 600-fold volume of 1.0 M H/sub 2/SO/sub 4/ solution lowers the solubility of petroleum sulfoxides from 1.26-1.02 to 0.12-0.10 g/liter. The conditions for extraction of PSO from aqueous solutions by kerosine were found, and it was shown that under these conditions the extraction of sulfoxides into kerosine reaches 85% in a single stage and more than 96% in three stages.

  20. Population genetics of concurrent selection with albendazole and ivermectin or diethylcarbamazine on the possible spread of albendazole resistance in Wuchereria bancrofti.

    PubMed

    Schwab, A E; Churcher, T S; Schwab, A J; Basáñez, M-G; Prichard, R K

    2006-11-01

    The Global Program for the Elimination of Lymphatic Filariasis (GPELF) intends to achieve its aims through yearly mass treatments with albendazole (ABZ) combined with ivermectin (IVM) or diethylcarbamazine (DEC). The use of ABZ and IVM separately to combat parasites of veterinary importance has, on many occasions, resulted in widespread drug resistance. In order to help predict the spread of potential ABZ resistance alleles through a population of Wuchereria bancrofti, we have developed a mathematical model that incorporates population genetics into EPIFIL, a model which examines the transmission dynamics of the parasite. Our model considers the effect of the combined treatments on the frequency of a recessive allele, which confers ABZ resistance. The model predicts that after 10 yearly treatments with ALB and DEC, 85% coverage and an initial resistance allele frequency of 5%, the frequency of the resistance genotype will increase from 0.25 to 12.7%. If non-random mating is assumed, the initial genotype frequency will be 2.34% and will increase to 62.7%. ABZ and IVM combination treatment may lead to weaker selection for this genotype. Treatment coverage, initial allele frequencies and number of treatments also affect the rate of selection.

  1. Molecular Chirality: Enantiomer Differentiation by High-Resolution Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hirota, Eizi

    2014-06-01

    I have demonstrated that triple resonance performed on a three-rotational-level system of a chiral molecule of C1 symmetry exhibits signals opposite in phase for different enantiomers, thereby making enantiomer differentiation possible by microwave spectroscopy This prediction was realized by Patterson et al. on 1,2-propanediol and 1,3-butanediol. We thus now add a powerful method: microwave spectroscopy to the study of chiral molecules, for which hitherto only the measurement of optical rotation has been employed. Although microwave spectroscopy is applied to molecules in the gaseous phase, it is unprecedentedly superior to the traditional method: polarimeter in resolution, accuracy, sensitivity, and so on, and I anticipate a new fascinating research area to be opened in the field of molecular chirality. More versatile and efficient systems should be invented and developed for microwave spectroscopy, in order to cope well with new applications expected for this method For C2 and Cn (n ≥ 3)chiral molecules, the three-rotational-level systems treated above for C1 molecules are no more available within one vibronic state. It should, however, be pointed out that, if we take into account an excited vibronic state in addition to the ground state, for example, we may encounter many three-level systems. Namely, either one rotational transition in the ground state is combined with two vibronic transitions, or such a rotational transition in an excited state may be connected through two vibronic transitions to a rotational level in the ground state manifold. The racemization obviously plays a crucial role in the study of molecular chirality. However, like many other terms employed in chemistry, this important process has been "defined" only in a vague way, in other words, it includes many kinds of processes, which are not well classified on a molecular basis. I shall mention an attempt to obviate these shortcomings in the definition of racemization and also to clarify the

  2. Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis

    PubMed Central

    Makunde, William H; Kamugisha, Leo M; Massaga, Julius J; Makunde, Rachel W; Savael, Zakana X; Akida, Juma; Salum, Fred M; Taylor, Mark J

    2003-01-01

    Background In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. Methods The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 μg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. Results In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co

  3. Recurrent Hemorrhagic Pericardial Effusion and Tamponade due to Filariasis Successfully Treated with Ivermectin and Albendazole.

    PubMed

    Sinha, Santosh Kumar; Goel, Amit; Sachan, Mohit; Saraf, Sameer; Verma, Chandra Mohan

    2015-01-01

    Filariasis presenting with pericardial effusion with tamponade is rare. We report a case of a 30-year-old female who was admitted with severe dyspnea and chest pain since 2 days. Echocardiogram showed massive pericardial effusion with tamponade. Pericardial fluid aspiration drained 1.2 L of hemorrhagic fluid. Cytology examination revealed microfilaria of Wuchereria bancrofti. She was treated with diethyl carbamazine and discharged. Six weeks later, she presented again with massive pericardial effusion with cardiac tamponade. Pericardiocentesis was done. Cytology examination revealed microfilaria of W. bancrofti. This time she was treated with ivermectin and albendazole and cured. Hemorrhagic effusion resolved completely. Though relatively uncommon, tropical diseases must always be considered in the etiological diagnosis of recurrent pericardial effusion.

  4. Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

    PubMed

    Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel

    2016-10-01

    Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.

  5. Effect of a controlled-release albendazole capsule on parasitism and productivity of sheep.

    PubMed

    Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L

    1991-11-01

    The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.

  6. Enhancement of the dissolution of albendazole from pellets using MTR technique

    PubMed Central

    Ibrahim, Mohamed A.; Al-Anazi, Fars K.

    2012-01-01

    Albendazole (ABZ), a broad-spectrum anthelmintic agent, is poorly absorbed after oral administration due to its low aqueous solubility. The aim of this study was to improve albendazole dissolution rate by formulating avicel pellets loaded with 10% w/w drug using extrusion/spheronization technique. In addition the wet masses were characterized by mix torque rheometry (MTR) prior to pelletization process. Different additives (i.e., lactose, Tween 80 and low molecular weight chitosan) were formulated with avicel to enhance the dissolution rate of ABZ from the produced pellets. Moreover, mix torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The produced pellets were characterized for their ABZ content, particle size, particle shape, dissolution profile and thermal behaviors. The maximum consistencies (the peak torques) of the wet granules were obtained using 0.667–1.333 ml/g of water or water containing surfactant. Also, the produced pellets have size range from 1036 to 1246 μm. The calculated drug RDR30 for 10%, 30% and 50% lactose concentrations were 1.08, 1.08 and 2.03, respectively, while that calculated for 10%, 30% and 50% w/w chitosan concentrations were 1.71, 3.62 and 3.62, respectively. The results revealed also that increasing the weight ratio of lactose and chitosan was accompanied by a significant reduction of the peak torque magnitude and this was accompanied by an enhanced ABZ dissolution rate. PMID:23960837

  7. In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

    PubMed

    Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

    2016-03-01

    Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole.

  8. The chiral herbicide beflubutamid (I): Isolation of pure enantiomers by HPLC, herbicidal activity of enantiomers, and analysis by enantioselective GC-MS.

    PubMed

    Buerge, Ignaz J; Bächli, Astrid; De Joffrey, Jean-Pierre; Müller, Markus D; Spycher, Simon; Poiger, Thomas

    2013-07-02

    For many chiral pesticides, little information is available on the properties and fate of individual stereoisomers. A basic data set would, first of all, include stereoisomer-specific analytical methods and data on the biological activity of stereoisomers. The herbicide beflubutamid, which acts as an inhibitor of carotenoid biosynthesis, is currently marketed as racemate against dicotyledonous weeds in cereals. Here, we present analytical methods for enantiomer separation of beflubutamid and two metabolites based on chiral HPLC. These methods were used to assign the optical rotation and to prepare milligram quantities of the pure enantiomers for further characterization with respect to herbicidal activity. In addition, sensitive analytical methods were developed for enantiomer separation and quantification of beflubutamid and its metabolites at trace level, using chiral GC-MS. In miniaturized biotests with garden cress, (-)-beflubutamid showed at least 1000× higher herbicidal activity (EC50, 0.50 μM) than (+)-beflubutamid, as determined by analysis of chlorophyll a in 5-day-old leaves. The agricultural use of enantiopure (-)-beflubutamid rather than the racemic compound may therefore be advantageous from an environmental perspective. In further biotests, the (+)-enantiomer of the phenoxybutanoic acid metabolite showed effects on root growth, possibly via an auxin-type mode of action, but at 100× higher concentrations than the structurally related herbicide (+)-mecoprop.

  9. 1,1′:4′,1′′-Terphenyl-2′,5′-dicarb­oxy­lic acid dimethyl sulfoxide-d 6 disolvate

    PubMed Central

    Pop, Lucian C.; Preite, Marcelo; Manriquez, Juan Manuel; Vega, Andrés; Chavez, Ivonne

    2012-01-01

    The asymmetric unit of the title solvate, C20H14O4·2C2D6OS, contains half of the substituted terephthalic acid mol­ecule and one solvent mol­ecule. The centroid of the central benzene ring in the acid mol­ecule is coincident with a crystallographic inversion center. Neither the carboxyl nor the phenyl substituents are coplanar with the central aromatic ring, showing dihedral angles of 53.18 (11) and 47.83 (11)°, respectively. The dimethyl sulfoxide solvent mol­ecules are hydrogen bonded to the carb­oxy­lic acid groups. PMID:22606132

  10. One-Pot Parallel Synthesis of Alkyl Sulfides, Sulfoxides, and Sulfones.

    PubMed

    Bogolubsky, Andrey V; Moroz, Yurii S; Mykhailiuk, Pavel K; Ostapchuk, Eugeniy N; Rudnichenko, Alexander V; Dmytriv, Yurii V; Bondar, Anna N; Zaporozhets, Olga A; Pipko, Sergey E; Doroschuk, Roman A; Babichenko, Liudmyla N; Konovets, Anzhelika I; Tolmachev, Andrey

    2015-06-08

    A simple and cost-effective one-pot parallel synthesis approach to sulfides, sulfoxides, and sulfones from thiourea was elaborated. The method combines two procedures optimized to the parallel synthesis conditions: alkylation of thiourea with alkyl chlorides and mono or full oxidation of in situ generated sulfides with H2O2 or H2O2-(NH4)2MoO4. The experimental set up required commonly used lab equipment: conventional oven and ultrasonic bath; the work up includes filtration or extraction with chloroform. The method was evaluated on an 81 member library of drug-like sulfides, sulfoxides, and sulfones yielding the compounds on a 30-300 mg scale. A small-scale synthesis of 2-(benzhydrylsulfinyl)acetamide (modafinil) utilizing our approach resulted in similar efficiency to the published procedures.

  11. Life detection using glucose and tetrasaccharide enantiomer pairs.

    PubMed

    Warmflash, David; Chu, Huanyi; Siefert, Johnathan; Fox, George E

    2009-04-01

    A life-detection system based on the expectation that any viable organism will utilize stereoisomers of a given compound asymmetrically is examined. Aqueous extracts of common soil, Mars regolith simulant JSC Mars-1, and suspensions of E. coli and S. cerevisiae were incubated with stereoisomer pairs. The enantiomeric pairs were either D- and L-glucose or a pair of chiral tetrasaccharides. Following an incubation period of 10 days, stereoisomeric selectivity is detectable with the glucose pair by mass spectrometry in extracts made from soil at 0.5 g/ml, in extracts made from JSC Mars-1 at 2.5 g/ml, and in cell suspensions down to 1.0 x 10(7) cells/ml. For the tetrasaccharide pair, stereoisomeric selectivity was detected in extracts made from 0.5 g/ml or more of common soil but not in JSC Mars-1 simulant. The effective sensitivity in extracts was 2.5 x 10(7) cells/ml or better for the glucose pair and 5.0 x 10(8) cells/ml or better for the tetrasaccharide pair. The sensitivity of the glucose pair was such that it could detect life in samples that would be found to be devoid of organic matter by the GCMS system carried by the Viking landers. The results demonstrate the utility of the approach in the search for biological activity on Mars. However, sensitivity is a function of the enantiomer pair used, and this might also be different for hypothetical martian organisms. Therefore, it will be necessary to characterize additional stereoisomeric pairs and, ultimately, to include several in a single test environment.

  12. Enantiomer fractions of chiral Perfluorooctanesulfonate (PFOS) in human sera.

    PubMed

    Wang, Yuan; Beesoon, Sanjay; Benskin, Jonathan P; De Silva, Amila O; Genuis, Stephen J; Martin, Jonathan W

    2011-10-15

    Perfluorooctane sulfonate (PFOS) is the most prominent perfluoroalkyl contaminant in humans and wildlife, but there is great uncertainty in exposure pathways, particularly with respect to the importance of PFOS-precursors (PreFOS). We explored the hypothesis that nonracemic proportions of chiral PFOS in serum are qualitative and semiquantitative biomarkers of human PreFOS exposure. A new chiral HPLC-MS/MS method was developed for alpha-perfluoromethyl branched PFOS (1m-PFOS, typically 2-3% of total PFOS) and applied to enantiomer fraction (EF) analysis in biological samples. In blood and tissues of rodents exposed subchronically to electrochemical PFOS, 1m-PFOS was racemic (EF = 0.485-0.511) and no evidence for enantioselective excretion was found in this model mammal. 1m-PFOS in serum of pregnant women, from Edmonton, was significantly nonracemic, with a mean EF (±standard deviation) of 0.432 ± 0.009, similar to pooled North American serum. In a highly exposed Edmonton family (mother, father, and 5 children) living in a house where ScotchGard had been applied repeatedly to carpet and upholstery, EFs ranged from 0.35 to 0.43, significantly more nonracemic than in pregnant women. Semiquantitative estimates of % serum 1m-PFOS coming from 1m-PreFOS biotransformation in both subpopulations were in reasonable agreement with model predictions of human exposure to PFOS from PreFOS. The data were overall suggestive that the measured nonracemic EFs were influenced by the relative extent of exposure to PreFOS. The possibility of using 1m-PFOS EFs for assessing the relative contribution of 1m-PreFOS (or PreFOS in general) in biological samples requires further application before being fully validated, but could be a powerful tool for probing general sources of PFOS in environments where the importance of PreFOS is unknown.

  13. Prevalence of soil-transmitted helminths after mass albendazole administration in an indigenous community of the Manu jungle in Peru.

    PubMed

    Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A

    2014-06-01

    Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5-19 years (51.8 %) and 20-35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5-19 years [odd ratio (OR) = 5.68; 95% CI: 2.71-11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon.

  14. Prevalence of soil-transmitted helminths after mass albendazole administration in an indigenous community of the Manu jungle in Peru

    PubMed Central

    Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A

    2014-01-01

    Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5–19 years (51.8 %) and 20–35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5–19 years [odd ratio (OR)  =  5.68; 95% CI: 2.71–11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon. PMID:24934795

  15. Determination of the impurities in drug products containing montelukast and in silico/in vitro genotoxicological assessments of sulfoxide impurity.

    PubMed

    Emerce, Esra; Cok, Ismet; Degim, I Tuncer

    2015-10-14

    Impurities affecting safety, efficacy, and quality of pharmaceuticals are of increasing concern for regulatory agencies and pharmaceutical industries, since genotoxic impurities are understood to play important role in carcinogenesis. The study aimed to analyse impurities of montelukast chronically used in asthma theraphy and perform genotoxicological assessment considering regulatory approaches. Impurities (sulfoxide, cis-isomer, Michael adducts-I&II, methylketone, methylstyrene) were quantified using RP-HPLC analysis on commercial products available in Turkish market. For sulfoxide impurity, having no toxicity data and found to be above the qualification limit, in silico mutagenicity prediction analysis, miniaturized bacterial gene mutation test, mitotic index determination and in vitro chromosomal aberration test w/wo metabolic activation system were conducted. In the analysis of different batches of 20 commercial drug products from 11 companies, only sulfoxide impurity exceeded qualification limit in pediatric tablets from 2 companies and in adult tablets from 7 companies. Leadscope and ToxTree programs predicted sulfoxide impurity as nonmutagenic. It was also found to be nonmutagenic in Ames MPF Penta I assay. Sulfoxide impurity was dose-dependent cytotoxic in human peripheral lymphocytes, however, it was found to be nongenotoxic. It was concluded that sulfoxide impurity should be considered as nonmutagenic and can be classified as ordinary impurity according to guidelines.

  16. Quantitative Determination of Lercanidipine Enantiomers in Commercial Formulations by Capillary Electrophoresis

    PubMed Central

    Lourenço, Luciana Pereira; Aguiar, Fernando Armani; de Oliveira, Anderson Rodrigo Moraes; de Gaitani, Cristiane Masetto

    2015-01-01

    An enantioselective method based on capillary electrophoresis (CE) using cyclodextrin (CD) as chiral selector was developed and validated for determination of lercanidipine (LER) enantiomers, a drug calcium channel blocker which exerts antihypertensive effects of long duration, in a pharmaceutical formulation. Optimum separation of LER enantiomers was obtained on a 50 cm × 50 μm id capillary using a sodium acetate buffer solution 200 mmol/L pH 4.0 containing 10 mmol/L of 2,3,6-o-methyl-β-cyclodextrin (TM-β-CD) as background electrolyte. The capillary temperature and voltage were 15°C and 25 kV, respectively, hydrodynamic injection and detection at 237 nm. Linearity was obtained in the range 12.5–100 μg/mL for both enantiomers (r ≥ 0.995). The RSD (%) and relative errors (E, %) obtained in precision and accuracy studies (intraday and interday) were lower than 5%. After validation, the method was applied to quantify the enantiomers of LER in commercial tablets and the results were satisfactory in terms of accuracy and precision, both less than 5%. Therefore, this method was found to be appropriate for enantioselective quality control of LER enantiomers in pharmaceutical formulations. PMID:25821632

  17. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers

    PubMed Central

    Xiao, Qi; Lu, Shuangyan; Huang, Chusheng; Su, Wei; Huang, Shan

    2016-01-01

    Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE), an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp) enantiomers was developed by differential pulse voltammograms (DPVs). Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C–N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C–N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications. PMID:27834863

  18. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers.

    PubMed

    Xiao, Qi; Lu, Shuangyan; Huang, Chusheng; Su, Wei; Huang, Shan

    2016-11-09

    Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE), an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp) enantiomers was developed by differential pulse voltammograms (DPVs). Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C-N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C-N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications.

  19. Differential field responses of the little fire ant, Wasmannia auropunctata (Roger), to alarm pheromone enantiomers.

    PubMed

    Yu, Yang; Jang, Eric B; Siderhurst, Matthew S

    2014-12-01

    The little fire ant, Wasmannia auropunctata (Roger) (Hymenoptera: Formicidae), is an invasive ant with negative impacts on both biodiversity and agriculture throughout the tropics and subtropics. Field experiments were conducted in order to elucidate the relative attractiveness of the enantiomers of the alarm pheromones, 2,5-dimethyl-3-(2-methylbutyl)pyrazine and 3-methyl-2-(2-methylbutyl)pyrazine. The enantiomers tested were synthesized from commercially available (S)-2-methylbutan-1-ol or kinetically resolved (R)-2-methylbutan-1-ol, prepared using Pseudomonas cepacia lipase (PCL). Bioassays conducted in a macadamia orchard on the island of Hawaii demonstrated that W. auropunctata were preferentially attracted to the (S)-enantiomers of both alkyl pyrazines over the racemic mixtures in all experiments. To our knowledge, this is the first instance of differential attraction of ants to the enantiomers of chiral pyrazine pheromones despite many examples of these compounds in the literature. In addition, using a chiral column it was determined that (S)-2,5-dimethyl-3-(2-methylbutyl)pyrazine and (S)-3-methyl-2-(2-methylbutyl)pyrazine are the only enantiomers produced by W. auropunctata.

  20. Enantioselective separation and determination of the dinotefuran enantiomers in rice, tomato and apple by HPLC.

    PubMed

    Chen, Xiu; Dong, Fengshou; Liu, Xingang; Xu, Jun; Li, Jing; Li, Yuanbo; Wang, Yunhao; Zheng, Yongquan

    2012-01-01

    An effective chiral analytical method was developed for the resolution and determination of dinotefuran enantiomers in rice, tomato and apple samples. Dinotefuran enantiomers were baseline-separated and determined on a novel chiral column, ChromegaChiral CCA, with n-hexane-ethanol-methanol (85:5:10, v/v/v) as the mobile phase at a flow rate of 1.0 mL/min with UV detection at 270 nm. The resolution of dinotefuran enantiomers was about 1.8. The first eluted enantiomer was (+)-dinotefuran and the second eluted one was (-)-dinotefuran. The effects of mobile-phase composition and column temperature on the enantioseparation were evaluated. The method was validated for linearity, repeatability, accuracy, LOD and LOQ. LOD was 0.15 mg/kg in rice and tomato, 0.05 mg/kg in apple, with an LOQ of 0.5 mg/kg in rice and tomato, 0.2 mg/kg in apple. The average recoveries of the pesticide from all matrices ranged from 75.8 to 92.9% for all fortification levels The precision values associated with the analytical method, expressed as RSD values, were <16.5% for the pesticide in all matrices. The methodology was successfully applied for the enantioselective analysis of dinotefuran enantiomers in real samples, indicating its efficiency in investigating the environmental stereochemistry of dinotefuran in food matrix.

  1. Gossypol enantiomers potently inhibit human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase activities.

    PubMed

    Dong, Yaoyao; Mao, Baiping; Li, Linxi; Guan, Hongguo; Su, Ying; Li, Xiaoheng; Lian, Qingquan; Huang, Ping; Ge, Ren-Shan

    2016-03-01

    Gossypol is a chemical isolated from cotton seeds. It exists as (+) or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+)- and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 μM, while (-) gossypol weakly inhibited it with IC50 over 100 μM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 μM, while (+) gossypol had no inhibition when the highest concentration (100 μM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects.

  2. Indirect chiral separation of tryptophan enantiomers by high performance liquid chromatography with indirect chemiluminiscence detection.

    PubMed

    Zhou, Jie; Chen, Shanshan; Sun, Fang; Luo, Pei; Du, Qiuzheng; Zhao, Suzhen

    2015-12-01

    In recent years, the study of chiral compounds in vivo has received much attention. In this study, a novel method based on high performance liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection was developed for the separation of tryptophan (Trp) enantiomers. o-Phthalaldehyde and N-acetyl-l-cysteine were used as chiral derivatization reagents for Trp before it can be detected by HPLC-CL method. The separation was carried out on an ODS column using a mobile phase composed of methanol-0.01mol/L phosphate buffer (40/60, v/v). Under the optimum conditions, satisfactory results were obtained, including complete separation, good relative standard deviations and low detection limits. The applicability of the proposed method has been validated by determining Trp in biological samples. Linear responses (r>0.9990) were observed over the range of 2.5×10(-7) to 1.2×10(-5)g/mL of Trp enantiomers, with quantitation limit of 2.5×10(-7)g/mL. The assay method shows good specificity to Trp enantiomers, and thus it will have great potential application in clinical diagnosis. The mean extraction efficiency of Trp enantiomers in mice plasma samples were 98.48% and 97.40%, respectively. The mean relative standard deviation (RSD) of Trp enantiomers were <3%.

  3. Axially chiral imidodiphosphoric Acid catalyst for asymmetric sulfoxidation reaction: insights on asymmetric induction.

    PubMed

    Jindal, Garima; Sunoj, Raghavan B

    2014-04-22

    Insights into chiral induction for an asymmetric sulfoxidation reaction involving a single oxygen atom transfer are gained through analyzing the stereocontrolling transition states. The fitting of the substrate into the chiral cavity of a new class of imidodiphosphoric Brønsted acids, as well as weak CH⋅⋅⋅π and CH⋅⋅⋅O noncovalent interactions, are identified as responsible for the observed chiral induction.

  4. Conference on Biological Actions and Medical Applications of Dimethyl Sulfoxide (DMSO), 15-17 September 1982.

    DTIC Science & Technology

    1983-06-01

    Toxicology of Dimethyl Sulfoxide and Effects on Retinitis Pigmentosa . By CHARLES A. GARCIA...indications with the addition of studies of the effect of DMSO on mental retardation, amyloidosis, retinitis pigmentosa , spinal cordl injury, cerebral edema...Experientia 36: 92. 1I r S., 5- 1 dM - 2 .,, 4 lmpmu OCULAR TOXICOLOGY OF DIMETHYL SUILFOXIDE AND EFFECTS ON RETINITIS PIGMENTOSA Charles A. Garcia" D

  5. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO).

    PubMed

    Nikolaou, Nikolaos; Green, Charlotte J; Gunn, Pippa J; Hodson, Leanne; Tomlinson, Jeremy W

    2016-11-01

    Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism. HepG2 cells were cultured in media containing 1% dimethyl sulfoxide for 2, 4, 7, 14, and 21 days. Gene expression, protein levels, intracellular triglyceride, and media concentrations of triglyceride, urea, and 3-hydroxybutyrate concentrations were measured. Dimethyl sulfoxide treatment altered the expression of genes involved in lipid (FAS, ACC1, ACC2, DGAT1, DGAT2, SCD) and glucose (PEPCK, G6Pase) metabolism as well as liver functionality (albumin, alpha-1-antitrypsin, AFP). mRNA changes were paralleled by alterations at the protein level. DMSO treatment decreased intracellular triglyceride content and lactate production and increased triglyceride and 3-hydroxybutyrate concentrations in the media in a time-dependent manner. We have demonstrated that the addition of 1% dimethyl sulfoxide to culture media changes the metabolic phenotype of HepG2 cells toward a more primary human hepatocyte phenotype. This will enhance the currently available in vitro model systems for the study of hepatocyte biology related to pathological processes that contribute to disease and their response to specific therapeutic interventions.

  6. Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

    PubMed Central

    Humphries, Debbie; Simms, Benjamin T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-01-01

    Children (n = 812) 6–11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564

  7. Hookworm infection among school age children in Kintampo north municipality, Ghana: nutritional risk factors and response to albendazole treatment.

    PubMed

    Humphries, Debbie; Simms, Benjamin T; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-09-01

    Children (n = 812) 6-11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana.

  8. The cost-effectiveness of ivermectin vs. albendazole in the presumptive treatment of strongyloidiasis in immigrants to the United States.

    PubMed Central

    Muennig, P.; Pallin, D.; Challah, C.; Khan, K.

    2004-01-01

    The presumptive treatment of parasitosis among immigrants with albendazole has been shown to save both money and lives, primarily via a reduction in the burden of Strongyloides stercoralis. Ivermectin is more effective than albendazole, but is also more expensive. This coupled with confusion surrounding the cost-effectiveness of guiding therapy based on eosinophil counts has led to disparate practices. We used the newly arrived year 2000 immigrant population as a hypothetical cohort in a decision analysis model to examine the cost-effectiveness of various interventions to reduce parasitosis among immigrants. When the prevalence of S. stercoralis is greater than 2%, the incremental cost-effectiveness ratios of all presumptive treatment strategies were similar. Ivermectin is associated with an incremental cost-effectiveness ratio of 1700 dollars per QALY gained for treatment with 12 mg ivermectin relative to 5 days of albendazole when the prevalence is 10%. Any presumptive treatment strategy is cost-effective when compared with most common medical interventions. PMID:15635962

  9. Modified β-Cyclodextrin Inclusion Complex to Improve the Physicochemical Properties of Albendazole. Complete In Vitro Evaluation and Characterization

    PubMed Central

    García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina

    2014-01-01

    The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084

  10. Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children.

    PubMed

    Fox, Leanne M; Furness, Bruce W; Haser, Jennifer K; Desire, Dardith; Brissau, Jean-Marc; Milord, Marie-Denise; Lafontant, Jack; Lammie, Patrick J; Beach, Michael J

    2005-07-01

    This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P < or = 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P < or = 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P < or = 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.

  11. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

    PubMed

    Gaballah, Samir T; El-Nezhawy, Ahmed O H; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2016-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

  12. Studies of a novel cysteine sulfoxide lyase from Petiveria alliacea: the first heteromeric alliinase.

    PubMed

    Musah, Rabi A; He, Quan; Kubec, Roman; Jadhav, Abhijit

    2009-11-01

    A novel alliinase (EC 4.4.1.4) was detected and purified from the roots of the Amazonian medicinal plant Petiveria alliacea. The isolated enzyme is a heteropentameric glycoprotein composed of two alpha-subunits (68.1 kD each), one beta-subunit (56.0 kD), one gamma-subunit (24.8 kD), and one delta-subunit (13.9 kD). The two alpha-subunits are connected by a disulfide bridge, and both alpha- and beta-subunits are glycosylated. The enzyme has an isoelectric point of 4.78 and pH and temperature optima of 8.0 and approximately 52 degrees C, respectively. Its activation energy with its natural substrate S-benzyl-l-cysteine sulfoxide is 64.6 kJ mol(-1). Kinetic studies showed that both K(m) and V(max) vary as a function of substrate structure, with the most preferred substrates being the naturally occurring P. alliacea compounds S-benzyl-l-cysteine sulfoxide and S-2-hydroxyethyl-l-cysteine sulfoxide. The alliinase reacts with these substrates to produce S-benzyl phenylmethanethiosulfinate and S-(2-hydroxyethyl) 2-hydroxyethanethiosulfinate, respectively.

  13. Oxygen atom transfer reactions from Mimoun complexes to sulfides and sulfoxides. A bonding evolution theory analysis.

    PubMed

    González-Navarrete, Patricio; Sensato, Fabricio R; Andrés, Juan; Longo, Elson

    2014-08-07

    In this research, a comprehensive theoretical investigation has been conducted on oxygen atom transfer (OAT) reactions from Mimoun complexes to sulfides and sulfoxides. The joint use of the electron localization function (ELF) and Thom's catastrophe theory (CT) provides a powerful tool to analyze the evolution of chemical events along a reaction pathway. The progress of the reaction has been monitored by structural stability domains from ELF topology while the changes between them are controlled by turning points derived from CT which reveal that the reaction mechanism can be separated in several steps: first, a rupture of the peroxo O1-O2 bond, then a rearrangement of lone pairs of the sulfur atom occurs and subsequently the formation of S-O1 bond. The OAT process involving the oxidation of sulfides and sulfoxides is found to be an asynchronous process where O1-O2 bond breaking and S-O1 bond formation processes do not occur simultaneously. Nucleophilic/electrophilic characters of both dimethyl sulfide and dimethyl sulfoxide, respectively, are sufficiently described by our results, which hold the key to unprecedented insight into the mapping of electrons that compose the bonds while the bonds change.

  14. Overexpression of methionine-R-sulfoxide reductases has no influence on fruit fly aging

    PubMed Central

    Shchedrina, Valentina A.; Vorbrüggen, Gerd; Cheon Lee, Byung; Kim, Hwa-Young; Kabil, Hadise; Harshman, Lawrence G.; Gladyshev, Vadim N.

    2009-01-01

    Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antioxidant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under calorie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized in any animal model systems. Here, the GAL4-UAS binary system was used to drive overexpression of cytosolic Drosophila MsrB and mitochondrial mouse MsrB2 in whole body, fatbody, and the nervous system of flies. In contrast to MsrA, MsrB overexpression had no consistent effect on the lifespan of fruit flies on both corn meal and sugar yeast diets. Physical activity, fecundity, and stress resistance were also similar in MsrB-overexpressing and control flies. Thus, MsrA and MsrB, the two proteins with identical function in antioxidant protein repair, have different effects on aging in fruit flies. PMID:19409408

  15. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    PubMed

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

  16. Chromatographic determination of amino acid enantiomers in beers and raw materials used for their manufacture.

    PubMed

    Erbe, T; Brückner, H

    2000-06-09

    Using gas chromatography (GC) on a chiral stationary phase, accompanied by high-performance liquid chromatography, beers and raw materials used for manufacturing (hops, barley grains, malts) were investigated for the pattern and quantities of amino acid enantiomers. Although L-amino acids were most abundant, certain D-amino acids were detected in all beers and most of the raw materials. Highest amounts of D-amino acids were detected in special beers such as Berliner Weisse that underwent bottle-conditioning with lactic cultures, and Belgian fruit beers produced by spontaneous fermentation. It is demonstrated that GC on chiral stationary phases is highly suitable for the quantitative determination of amino acid enantiomers in beers and raw materials used for their manufacture. Quantities, relative amounts and pattern of amino acid enantiomers can serve in particular as chiral markers for the authenticity of special beers.

  17. Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

    NASA Astrophysics Data System (ADS)

    Tang, Jian; Zhang, Shapopeng; Lin, Yuzhou; Zhou, Jie; Pang, Limin; Nie, Xuemei; Zhou, Baojing; Tang, Weihua

    2015-08-01

    The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities.

  18. Disposition and absorption of hydroxychloroquine enantiomers following a single dose of the racemate.

    PubMed

    McLachlan, A J; Tett, S E; Cutler, D J; Day, R O

    1994-01-01

    The disposition of hydroxychloroquine enantiomers has been investigated in nine patients with rheumatoid arthritis following administration of a single dose of the racemate. Blood concentrations of (-)-(R)-hydroxychloroquine exceed those of (+)-(S)-hydroxychloroquine following both an oral and intravenous dose of the racemate. Maximum blood concentrations of (-)-(R)-hydroxychloroquine were higher than (+)-(S)-hydroxychloroquine after oral dosing (121 +/- 56 and 99 +/- 42 ng/ml, respectively, P = 0.009). The time to maximum concentration and the absorption half-life, calculated using deconvolution techniques, were similar for both enantiomers. The fractions of the dose of each enantiomer absorbed were similar, 0.74 and 0.77 for (-)-(R)- and (+)-(S)-hydroxychloroquine, respectively (P = 0.77). The data suggest that absorption of hydroxychloroquine is not enantioselective. The stereoselective disposition of hydroxychloroquine appears to be due to enantioselective metabolism and renal clearance, rather than stereoselectivity in absorption and distribution.

  19. Determination of fluoxetine enantiomers in pharmaceutical formulations by electrokinetic chromatography-counter current technique.

    PubMed

    Asensi-Bernardi, Lucía; Martín-Biosca, Yolanda; Fornet-Herrero, Eder; Sagrado, Salvador; Medina-Hernández, María José

    2013-03-01

    In this work, an electrokinetic chromatography-counter current procedure for the separation of fluoxetine enantiomers using highly sulfated β-cyclodextrin was optimized and applied to the determination of the enantiomers in three pharmaceutical formulations according to the matrix features. Quality criteria were applied to facilitate its transferability to testing laboratories. Fluoxetine was used therapeutically as the racemate, although a stereospecificity associated with its interactions with the neuronal serotonin-uptake carrier was demonstrated. In this context, the development of enantioselective methods for the chiral analysis of pharmaceuticals allowing stereoisomer ratio estimations has increasing interest in pharmaceutical industry. The proposed method allows the quantification of both enantiomers in less than 2 min with high resolution (R(s) = 2.4).

  20. LIQUID CHROMATOGRAPHIC SEPARATION OF THE ENANTIOMERS OF TRANS-CHLORDANE, CIS-CHLORDANE, HEPTACHLOR, HEPTACHLOR EPOXIDE AND ALPHA-HEXACHLOROCYCLOHEXANE WITH APPLICATION TO SMALL-SCALE PREPARATIVE SEPARATION

    EPA Science Inventory

    Analytical high-performance liquid chromatographic separations of the individual enantiomers of five polychlorinated compounds were obtained on polysaccharide stereoselective HPLC columns. The enantiomers of the pesticides trans-chlordane, cis-chlordane and heptachlor were separa...

  1. Toxicokinetics of tabun enantiomers in anaesthetized swine after intravenous tabun administration.

    PubMed

    Tenberken, O; Mikler, J; Hill, I; Weatherby, K; Thiermann, H; Worek, F; Reiter, G

    2010-10-05

    In the present study, we report the first in vivo toxicokinetic study of tabun (O-ethyl-N,N-dimethylphosphoramidocyanidate). The toxicokinetics of the enantiomers of tabun were investigated in anesthetized swine after intravenous administration of 3xLD(50) (161.4mug/kg) tabun. Blood samples were taken for gas chromatographic-mass spectrometric determination of the tabun enantiomers and for measurement of the activity of red blood cell acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE). The tabun enantiomers could be quantified in swine blood to a minimum concentration of 3.0pg/ml (18.5pM) and could be detected to a minimum concentration of 1.0pg/ml (6.2pM). The concentration-time profiles of both tabun enantiomers were best described by a bi-exponential equation. The elimination of (+)-tabun and (-)-tabun were comparable in the initial phase. In the terminal phase a remarkable difference was found, with terminal half lives of 11.5min for (+)-tabun and 23.1min for (-)-tabun. (+)-Tabun showed a markedly longer persistence in vivo than (+)-enantiomers of other G-type nerve agents and could be detected in all swine at least up to 30min post-injection, (-)-tabun at least up to 90min post-injection. These results demonstrate a rather rapid elimination of tabun enantiomers in vivo and may provide a toxicokinetic basis for the further development and optimization of medical countermeasures against this nerve agent.

  2. Biological activities of α-pinene and β-pinene enantiomers.

    PubMed

    da Silva, Ana Cristina Rivas; Lopes, Paula Monteiro; de Azevedo, Mariana Maria Barros; Costa, Danielle Cristina Machado; Alviano, Celuta Sales; Alviano, Daniela Sales

    2012-05-25

    The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with MICs ranging from 117 to 4,150 µg/mL. However, no antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL. Time-kill curves showed that (+)-a-pinene and (+)-β-pinene were highly toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast, the bactericidal effect occurred after 6 h in methicillin-resistant Staphylococcus aureus (MRSA). In combination with commercial antimicrobials, ciprofloxacin plus (+)-a-pinene or (+)-β-pinene presented synergistic activity against MRSA whereas an indifferent effect against all fungi was detected when amphotericin B was combined with the positive enantiomers of pinene. The potential of (+)-a-pinene and (+)-β-pinene to inhibit phospholipase and esterase activities was also evaluated, and the best inhibition results were obtained with Cryptococcus neoformans. C. albicans biofilm formation was prevented with the MIC concentration of (+)-a-pinene and twice the MIC value of (+)-β-pinene. Finally, the cytotoxicity of the positive enantiomers of pinene to murine macrophages was evaluated, and 250 µg/mL of (+)-a-pinene and (+)-β-pinene reduced the cell viability to 66.8% and 57.7%, respectively.

  3. Biological activities of α-pinene and β-pinene enantiomers.

    PubMed

    Rivas da Silva, Ana Cristina; Lopes, Paula Monteiro; Barros de Azevedo, Mariana Maria; Costa, Danielle Cristina Machado; Alviano, Celuta Sales; Alviano, Daniela Sales

    2012-05-25

    The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the α- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with MICs ranging from 117 to 4,150 μg/mL. However, no antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL. Time-kill curves showed that (+)-α-pinene and (+)-β-pinene were highly toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast, the bactericidal effect occurred after 6 h in methicillin-resistant Staphylococcus aureus (MRSA). In combination with commercial antimicrobials, ciprofloxacin plus (+)-α-pinene or (+)-β-pinene presented synergistic activity against MRSA whereas an indifferent effect against all fungi was detected when amphotericin B was combined with the positive enantiomers of pinene. The potential of (+)-α-pinene and (+)-β-pinene to inhibit phospholipase and esterase activities was also evaluated, and the best inhibition results were obtained with Cryptococcus neoformans. C. albicans biofilm formation was prevented with the MIC concentration of (+)-α-pinene and twice the MIC value of (+)-β-pinene. Finally, the cytotoxicity of the positive enantiomers of pinene to murine macrophages was evaluated, and 250 μg/mL of (+)-α-pinene and (+)-β-pinene reduced the cell viability to 66.8% and 57.7%, respectively.

  4. Characterization of triacylglycerol enantiomers using chiral HPLC/APCI-MS and synthesis of enantiomeric triacylglycerols.

    PubMed

    Lísa, Miroslav; Holčapek, Michal

    2013-02-05

    In this work, the first systematic characterization of triacylglycerol (TG) enantiomers in real samples using chiral high-performance liquid chromatography (HPLC) with atmospheric pressure chemical ionization mass spectrometry (APCI-MS) is performed. Our chiral HPLC/APCI-MS method is based on the use of two cellulose-tris-(3,5-dimethylphenylcarbamate) columns connected in series using a gradient of hexane-2-propanol mobile phase. All TG enantiomers containing 1-8 DBs and different fatty acyl chain lengths are separated using our chiral HPLC method except for TGs having a combination of saturated and di- or triunsaturated fatty acyls in sn-1 and sn-3 positions. In our work, the randomization reaction of monoacyl TG standards is used for the preparation of all TG enantiomers and regioisomers in a mixture, while the stereospecific esterification of 1,2- or 2,3-isopropylidene-sn-glycerols by selected fatty acids is used for the synthesis of TG enantiomers. The composition of TG enantiomers and regioisomers in hazelnut oil and human plasma samples is determined. Unsaturated fatty acids are preferentially esterified in sn-2 position in hazelnut oil, while no significant preference of saturated or unsaturated fatty acyls is observed in case of human plasma sample. Fatty acids with the higher number of DBs are preferred in sn-1 position of TG enantiomers in hazelnut oil unlike to moderate sn-3 preference in human plasma. The characterization of cholesteryl esters from TG fraction of human plasma sample using our chiral HPLC/APCI-MS method is presented as well.

  5. In vitro and in vivo vasodilatory activity of barnidipine and its enantiomers.

    PubMed

    Inagaki, O; Asano, M; Takenaka, T

    1999-02-01

    Barnidipine, (3'S)-1-benzyl-3-pyrrolidinyl methyl (4S)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylat e, is a dihydropyridine calcium antagonist with asymmetric carbons at the dihydropyridine C-4 and the pyrrolidine C-3' positions. In this study, the vasodilatory activity of barnidipine and its 3 optical isomers were compared in vitro and in vivo to assess the steric effects of these asymmetric carbons. All these enantiomers produced concentration-dependent relaxation on KCI (40 mM)-induced contractions in isolated guinea pig aorta with a potency order of barnidipine>(3'R,4R) approximately/= (3'R,4S)>(3'S,4R). The potency ratio between barnidipine and the (3'S,4R) enantiomer was 118. All enantiomers increased coronary blood flow after intra-arterial administration to anesthetized coronary-perfused dogs. The potency order almost agreed with that obtained in vitro, although the potency ratio between barnidipine and the (3'S,4R) enantiomer was only 15. These 4 enantiomers showed stereoselectivity for time course changes as well. The onset and disappearance of blood flow increase after intracoronary administration of barnidipine were slower than those of other enantiomers. The duration for barnidipine was longer than those for other dihydropyridine calcium antagonists such as nifedipine or nitrendipine. The present study suggests stereoselectivity for the C-4 dihydropyridine and to a lesser degree for the C-3' of pyrrolidine in an ester moiety. The steric effects of these carbons were observed not only in the potency of vasodilatory activity but also in its duration.

  6. Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase

    PubMed Central

    Bourne, Christina R.; Wakeham, Nancy; Nammalwar, Baskar; Tseitin, Vladimir; Bourne, Philip C.; Barrow, Esther W.; Mylvaganam, Shankari; Ramnarayan, Kal; Bunce, Richard A.; Berlin, K. Darrell; Barrow, William W.

    2012-01-01

    Background Bacterial resistance to antibiotic therapies is increasing and new treatment options are badly needed. There is an overlap between these resistant bacteria and organisms classified as likely bioterror weapons. For example, Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to sequence changes found in the dihydrofolate reductase enzyme. Development of new inhibitors provides an opportunity to enhance the current arsenal of anti-folate antibiotics while also expanding the coverage of the anti-folate class. Methods We have characterized inhibitors of Bacillus anthracis dihydrofolate reductase by measuring the Ki and MIC values and calculating the energetics of binding. This series contains a core diaminopyrimidine ring, a central dimethoxybenzyl ring, and a dihydrophthalazine moiety. We have altered the chemical groups extended from a chiral center on the dihydropyridazine ring of the phthalazine moiety. The interactions for the most potent compounds were visualized by X-ray structure determination. Results We find that the potency of individual enantiomers is divergent with clear preference for the S-enantiomer, while maintaining a high conservation of contacts within the binding site. The preference for enantiomers seems to be predicated largely by differential interactions with protein residues Leu29, Gln30 and Arg53. Conclusions These studies have clarified the activity of modifications and of individual enantiomers, and highlighted the role of the less-active R-enantiomer in effectively diluting the more active S-enantiomer in racemic solutions. This directly contributes to the development of new antimicrobials, combating trimethoprim resistance, and treatment options for potential bioterrorism agents. PMID:22999981

  7. Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin.

    PubMed Central

    Screnci, D.; Er, H. M.; Hambley, T. W.; Galettis, P.; Brouwer, W.; McKeage, M. J.

    1997-01-01

    The diaminocyclohexane platinum (Pt(DACH)) derivatives ormaplatin and oxaliplatin have caused severe and dose-limiting peripheral sensory neurotoxicity in a clinical trial. We hypothesized that this toxicity could vary in relation to the biotransformation and stereochemistry of these Pt(DACH) derivatives. We prepared pure R,R and S,S enantiomers of ormaplatin (Pt(DACH)Cl4), oxaliplatin (Pt(DACH)oxalato) and their metabolites (Pt(DACH)Cl2 and Pt(DACH)methionine) and assessed their peripheral sensory neurotoxicity and tissue distribution in the rat and in vitro anti-tumour activity in human ovarian carcinoma cell lines. The R,R enantiomers of Pt(DACH)Cl4, Pt(DACH)oxalato and Pt(DACH)Cl2, induced peripheral sensory neurotoxicity at significantly lower cumulative doses (18 +/- 5.7 vs 32 +/- 2.3 micromol kg(-1); P < 0.01) and at earlier times (4 +/- 1 vs 6.7 +/- 0.6 weeks; P = 0.016) during repeat-dose treatment than the S,S enantiomers. Pt(DACH)methionine enantiomers showed no biological activity. There was no difference between Pt(DACH) enantiomers in the platinum concentration in sciatic nerve, dorsal root ganglia, spinal cord, brain or blood at the end of each experiment. Three human ovarian carcinoma cell lines (41 M, 41 McisR and SKOV-3) showed no (or inconsistent) chiral discrimination in their sensitivity to Pt(DACH) enantiomers, whereas two cell lines (CH-1 and CH-1cisR) showed modest enantiomeric selectivity favouring the R,R isomer (more active). In conclusion, Pt(DACH) derivatives exhibit enantiomeric-selective peripheral sensory neurotoxicity during repeated dosing in rats favouring S,S isomers (less neurotoxic). They exhibited less chiral discrimination in their accumulation within peripheral nerves and in vitro anti-tumour activity. PMID:9275028

  8. Separation and Measurement of Plant Alkaloid Enantiomers by RP-HPLC Analysis of their Fmoc-Alanine Analogs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants often synthesize secondary metabolites that are enantiomers. Enantiomers can cause very different physiological responses. Ammodendrine (1) and anabasine (2) are teratogens that can cause congenital malformations in livestock and enantiomeric forms of each have been found in Lupinus spp. an...

  9. Chiral recognition of Propranolol enantiomers by β-Cyclodextrin: Quantum chemical calculation and molecular dynamics simulation studies

    NASA Astrophysics Data System (ADS)

    Ghatee, Mohammad Hadi; Sedghamiz, Tahereh

    2014-12-01

    Enantiomeric recognition of Propranolol by complexation with β-Cyclodextrin was studied by PM3 method and molecular dynamics (MD) simulation. Gas phase results show that the R-enantiomer complex is more stable than the S-enantiomer complex by 8.54 kJ/mol (Hartree-Fock energy). Using polarized continuum model, solution phase of R-enantiomer complex was found to be more stable than S-enantiomer complex by 25.95 kJ/mol. Both complexes hardly occur at room temperature free-energy-wise, though, complexation with R-enantiomer is more favorable than with S-enantiomer enthalpy-wise. Also, complexes were studied by molecular dynamics simulation in gas and solution phases. More stability of R-enantiomer complex in gas phase is confirmed by MD van der Waals energy (5.04 kJ/mol) and closely by the counterpart PM3 binding energy (8.54 kJ/mol). Simulation in solution phase indicates more stability of R-enantiomer complex. Finally, simulated transport property provides insight into the high anisotropic atoms motion according to which S-Propranolol found possessing significantly higher dynamics.

  10. Plasma concentrations of the enantiomers of halofantrine and its main metabolite in malaria patients.

    PubMed

    Gimenez, F; Gillotin, C; Basco, L K; Bouchaud, O; Aubry, A F; Wainer, I W; Le Bras, J; Farinotti, R

    1994-01-01

    The plasma concentrations of the enantiomers of halofantrine and its N-desbutyl metabolite in six patients with malaria were measured after oral administration of 3 x 750 mg doses of micronised, racemic halofantrine hydrochloride given at 6-hour intervals. Significant differences were observed between the plasma concentrations of the enantiomers both of halofantrine and its N-monodesbutyl metabolite. AUC(0)84h values were higher for (+)halofantrine (9917 micrograms.ml-1.h) than for (-)-halofantrine (6127 micrograms.ml-1.h). The clinical significance of these observations is not known. The isomers have equipotent activity in vitro but their relative toxicity has not yet been assessed.

  11. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases

    PubMed Central

    Oprea, Tudor I.; Sklar, Larry A.; Agola, Jacob O.; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G.; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses—using the rotationally constrained carboxylate in R-naproxen—led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  12. Synthesis of the Enantiomers of Tedanalactam and the First Total Synthesis and Configurational Assignment of (+)-Piplaroxide.

    PubMed

    Romero-Ibañez, Julio; Xochicale-Santana, Leonardo; Quintero, Leticia; Fuentes, Lilia; Sartillo-Piscil, Fernando

    2016-04-22

    Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additionally, the (+)- and (-)-enantiomers of piplaroxide were obtained from their respective tedanalactam precursor, and the absolute configuration of the naturally occurring (+)-piplaroxide was determined. The present approach represents not only the shortest synthesis of (-)-tedanalactam but also the first total synthesis of (+)-piplaroxide, a repellent against the leafcutter ant Atta cephalotes.

  13. Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

    PubMed

    Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

    2004-09-01

    Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and

  14. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

    PubMed Central

    Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

    2017-01-01

    The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial

  15. Embryonation and infectivity of Ascaris suum eggs isolated from worms expelled by pigs treated with albendazole , pyrantel pamoate, ivermectin or piperazine dihydrochloride.

    PubMed

    Boes, J; Eriksen, L; Nansen, P

    1998-02-28

    The effect of anthelmintic treatment of pigs on the embryonation and infectivity of Ascaris suum eggs isolated from expelled worms was investigated. Four groups of two naturally infected pigs were dosed with albendazole, pyrantel pamoate, ivermectin or piperazine dihydrochloride, respectively. Following worm expulsion, the eggs were removed from the uteri of female worms and embryonated in sulphuric acid. The infectivity of the embryonated eggs was tested through mouse inoculation. Egg development appeared normal in cultures from worms of the piperazine. pyrantel and ivermectin treated groups. In the albendazole cultures, egg development was largely arrested at the one-cell stage (81%). Where development occurred, irregular cell division was observed and only 7% of the eggs in the culture developed into fullgrown larvae. Following mouse inoculation with 2500 embryonated eggs, significantly lower lung larval counts on day 8 post inoculation (p.i.) were observed for mice in the piperazine and pyrantel treated groups (P < 0.01) compared to untreated controls. The larvae that developed in the eggs from ivermectin and albendazole treated groups appeared fully infective for mice. It was concluded that ovicidal activity of albendazole in vivo inhibits subsequent A. suum egg development in vitro; albendazole is, therefore, not suitable to obtain worms for egg embryonation to produce experimental inoculums. The anthelmintic treatment of pigs with ivermectin had only a limited effect on both embryonation and infectivity of A. suum eggs isolated from expelled worms.

  16. Simultaneous extraction and quantification of albendazole and triclabendazole using vortex-assisted hollow-fiber liquid-phase microextraction combined with high-performance liquid chromatography.

    PubMed

    Asadi, Mohammad; Haji Shabani, Ali Mohammad; Dadfarnia, Shayessteh

    2016-06-01

    A novel, simple, and rapid vortex-assisted hollow-fiber liquid-phase microextraction method was developed for the simultaneous extraction of albendazole and triclabendazole from various matrices before their determination by high-performance liquid chromatography with fluorescence detection. Several factors influencing the microextraction efficiency including sample pH, nature and volume of extraction solvent, ionic strength, vortex time, and sample volume were investigated and optimized. Under the optimal conditions, the limits of detection were 0.08 and 0.12 μg/L for albendazole and triclabendazole, respectively. The calibration curves were linear in the concentration ranges of 0.3-50.0 and 0.4-50.0 μg/L with the coefficients of determination of 0.9999 and 0.9995 for albendazole and triclabendazole, respectively. The interday and intraday relative standard deviations for albendazole and triclabendazole at three concentration levels (1.0, 10.0, and 30.0 μg/L) were in the range of 6.0-11.0 and 5.0-7.9%, respectively. The developed method was successfully applied to determine albendazole and triclabendazole in water, milk, honey, and urine samples.

  17. Kinetics and thermodynamics of oxidation mediated reaction in L-cysteine and its methyl and ethyl esters in dimethyl sulfoxide-d6 by NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Dougherty, Ryan J.; Singh, Jaideep; Krishnan, V. V.

    2017-03-01

    L-Cysteine (L-Cys), L-Cysteine methyl ester (L-CysME) or L-Cysteine ethyl ester (L-CysEE), when dissolved in dimethyl sulfoxide, undergoes an oxidation process. This process is slow enough and leads to nuclear magnetic resonance (NMR) spectral changes that could be monitored in real time. The oxidation mediated transition is modeled as a pseudo-first order kinetics and the thermodynamic parameters are estimated using the Eyring's formulation. L-Cysteine and their esters are often used as biological models due to the remarkable thiol group that can be found in different oxidation states. This oxidation mediated transition is due to the combination of thiol oxidation to a disulfide followed by solvent-induced effects may be relevant in designing cysteine-based molecular models.

  18. Dramatic improvement in dissolution rate of albendazole by a simple, one-step, industrially scalable technique

    PubMed Central

    Ghanbarzadeh, Saeed; Khalili, Aram; Jouyban, Abolghasem; Emami, Shahram; Javadzadeh, Yousef; Solhi, Mohammad; Hamishehkar, Hamed

    2016-01-01

    Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ) is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5%) which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose), polyols (mannitol and sorbitol), ionic surfactant (sodium lauryl sulfate) and non-ionic surfactant (Cremophor A25) were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation), a great improvement (21 folds) in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system. PMID:28003836

  19. Spray drying formulation of albendazole microspheres by experimental design. In vitro-in vivo studies.

    PubMed

    García, Agustina; Leonardi, Darío; Piccirilli, Gisela N; Mamprin, María E; Olivieri, Alejandro C; Lamas, María C

    2015-02-01

    Both an experimental design and optimization techniques were carried out for the development of chitosan-pectin-carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60 min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug.

  20. Efficacy of albendazole against Taenia multiceps larvae in experimentally infected goats.

    PubMed

    Afonso, Sónia M S; Neves, Luis; Pondja, Alberto; Macuamule, Cristiano; Mukaratirwa, Samson; Arboix, Margarita; Cristòfol, Carles; Capece, Bettencourt P S

    2014-12-15

    A controlled trial was conducted to evaluate the efficacy of three therapeutics regimes of albendazole (ABZ) against Taenia multiceps larvae in experimental infected goats. Forty-nine goats experimentally infected with 3000 T. multiceps eggs were selected and randomly divided into treatment or control groups. Treatment with 10mg/kg for 3 days for group 1 (G1), 10mg/kg for group 2 (G2) and 20mg/kg/day for group 3 (G3) was applied 2 months after infection; group 4 (G4) served as a control group. A treatment with doses of 10mg/kg/day for 3 days on group 5 (G5) and group 6 (G6) was used as control, 5 months after the infection. The efficacy of ABZ was assessed as percentage of non-viable cysts which were determined by morphologic characteristics, movement and methyl blue staining technique. The efficacy of ABZ against 2 months old cysts was significantly different from the control and were 90.3% (28/31), 72.7% (8/11) and 73.9% (14/19) for G1, G2 and G3, respectively. No differences were observed in cyst viability between treated and control groups for 5-month old cysts. The results in this study indicate that ABZ is effective in goats against 2-month-old cysts of T. multiceps larva located in tissues outside the brain.

  1. A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties.

    PubMed

    Martinez-Marcos, Laura; Lamprou, Dimitrios A; McBurney, Roy T; Halbert, Gavin W

    2016-02-29

    The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect.

  2. Bancroftian filariasis: effect of repeated treatment with diethylcarbamazine and albendazole on microfilaraemia, antigenaemia and antifilarial antibodies.

    PubMed

    Helmy, Hanan; Weil, Gary J; Ellethy, Abou Sree T; Ahmed, Ehab S; Setouhy, Maged El; Ramzy, Reda M R

    2006-07-01

    Diethylcarbamazine/albendazole (DEC/ALB) therapy is widely used in mass drug administration (MDA) programmes aimed at eliminating lymphatic filariasis. We studied the effects of repeated annual treatments with DEC/ALB on Wuchereria bancrofti microfilaraemia, filarial antigenaemia and IgG4 antibodies to Bm14 antigen. Fifty-seven subjects with asymptomatic microfilaraemia were treated with one or seven daily doses of DEC/ALB at time zero. All subjects were re-treated with single-dose DEC/ALB 12, 24 and 36 months later. The two treatment groups had comparable pre-treatment microfilaria counts. Multidose treatment cleared microfilaraemia more effectively than single-dose treatment. Filarial antigen levels decreased equally in both treatment groups. Total antigen clearance was observed in 29.6%, 52.0%, 63.6% and 79.5% of subjects at 12, 24, 36 and 48 months. These clearance rates are much higher than those observed in prior treatment trials with DEC or ivermectin. Antibody levels increased 4 weeks after treatment and then slowly decreased in most subjects. Antibody tests turned negative in 20%, 35%, 39.4% and 52.5% of treated subjects at 12, 24, 36 and 48 months post treatment. These results show that the studied parameters decline at different rates and to differing degrees following DEC/ALB treatment. These findings have important implications regarding strategies for monitoring the effects of MDA in populations.

  3. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

    PubMed

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-02-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.

  4. Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis

    PubMed Central

    Zhang, Xuan; Zhao, Jing; Gao, Xiangyang; Pei, Dongsheng; Gao, Chao

    2017-01-01

    As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis. PMID:28352336

  5. Functioning methionine sulfoxide reductases A and B are present in human epidermal melanocytes in the cytosol and in the nucleus

    SciTech Connect

    Schallreuter, Karin U.; Chavan, Bhaven; Gillbro, Johanna M.

    2006-03-31

    Oxidation of methionine residues by reactive oxygen (ROS) in protein structures leads to the formation of methionine sulfoxide which can consequently lead to a plethora of impaired functionality. The generation of methionine sulfoxide yields ultimately a diastereomeric mixture of the S and R sulfoxides. So far two distinct enzyme families have been identified. MSRA reduces methionine S-sulfoxide, while MSRB reduces the R-diastereomer. It has been shown that these enzymes are involved in regulation of protein function and in elimination of ROS via reversible methionine formation besides protein repair. Importantly, both enzymes require coupling to the NADPH/thioredoxin reductase/thioredoxin electron donor system. In this report, we show for First time the expression and function of both sulfoxide reductases together with thioredoxin reductase in the cytosol as well as in the nucleus of epidermal melanocytes which are especially sensitive to ROS. Since this cell resides in the basal layer of the epidermis and its numbers and functions are reduced upon ageing and for instance also in depigmentation processes, we believe that this discovery adds an intricate repair mechanism to melanocyte homeostasis and survival.

  6. Sulfoxide stimulation of chondrogenesis in limb mesenchyme is accompanied by an increase in type II collagen enhancer activity

    SciTech Connect

    Horton, W.E. Jr.; Higginbotham, J.D. )

    1991-05-01

    We have utilized a modification of the limb bud mesenchyme micromass culture system to screen compounds that might stimulate chondrogenesis. Two compounds in the sulfoxide family (methylphenylsulfoxide and p-chlorophenyl methyl sulfoxide) were stimulatory at 10(-2) M and 10(-3) M, respectively; whereas other sulfoxides and organic solvents were not active at these concentrations. In addition, specific growth factors (basic FGF, IGF-I, IGF-II) were not chondroinductive at concentrations that are active in other cell systems. Both sulfoxide compounds stimulated cartilage nodule formation, ({sup 35}S)sulfate incorporation, and activity of the regulatory sequences of the collagen II gene. In contrast, transforming growth factor beta-1 (10 ng/ml) stimulated sulfate incorporation but produced only a diffuse deposition of cartilage matrix and reduced the ability of the cells to utilize the regulatory sequences of the collagen II gene. The sulfoxides appear to promote the differentiation of limb bud cells to chondrocytes and thus exhibit chondroinductive activity.

  7. Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites

    NASA Astrophysics Data System (ADS)

    Cooper, George; Rios, Andro C.

    2016-06-01

    Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (˜4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers.

  8. Determination of fexofenadine enantiomers in human plasma with high-performance liquid chromatography.

    PubMed

    Miura, Masatomo; Uno, Tsukasa; Tateishi, Tomonori; Suzuki, Toshio

    2007-01-17

    A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in human plasma. Fexofenadine enantiomers were separated using a mobile phase of 0.5% KH(2)PO(4)-acetonitrile (65:35, v/v) on a Chiral CD-Ph column at a flow rate of 0.5 ml/min and measurement at 220 nm. Analysis required 400 microl of plasma and involved solid-phase extraction with an Oasis HLB cartridge, which gave recoveries for both enantiomers from 67.4 to 71.8%. The lower limit of quantification was 25 ng/ml for (R)- and (S)-fexofenadine. The linear range of this assay was between 25 and 625 ng/ml (regression line r(2)>0.993). Inter- and intra-day coefficients of variation were less than 13.6% and accuracies were within 8.8% over the linear range for both analytes. This method can be applied effectively to measure fexofenadine enantiomer concentrations in clinical samples.

  9. Experiment and modeling for the separation of guaifenesin enantiomers using simulated moving bed and Varicol units.

    PubMed

    Gong, Rujin; Lin, Xiaojian; Li, Ping; Yu, Jianguo; Rodrigues, Alirio E

    2014-10-10

    The separation of guaifenesin enantiomers by both simulated moving bed (SMB) process and Varicol process was investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenylcarbamate (Chiralcel OD) stationary phase and a mixture of n-hexane and ethanol was used as mobile phase. The operation conditions were designed based on the separation region with the consideration of mass transfer resistance and axial dispersion, and the experiments to separate guaifenesin enantiomers were carried out on VARICOL-Micro unit using SMB process with the column configuration of 1/2/2/1 and Varicol process with the column configuration of 1/1.5/1.5/1, respectively. Single enantiomer with more than 99.0% purity was obtained in both processes with the productivity of 0.42 genantiomer/dcm(3) CSP for SMB process and 054 genantiomer/dcm(3) CSP for Varicol process. These experimental results obtained from SMB and Varicol processes were compared with those reported from literatures. In addition, according to the numerical simulation, the effects of solid-film mass transfer resistance and axial dispersion on the internal profiles were discussed, and the effect of column configuration on the separation performance of SMB and Varicol processes was analyzed for a few columns system. The feasibility and efficiency for the separation of guaifenesin enantiomers by SMB and Varicol processes were evaluated.

  10. Comparative disposition of ricobendazole enantiomers after intravenous and subcutaneous administration of a racemic formulation to calves.

    PubMed

    Cristòfol, C; Virkel, G; Alvarez, L; Arboix, M; Lanusse, C E

    2000-11-01

    The enantioselective disposition kinetics of the benzimidazole anthelmintic, ricobendazole (RBZ), have been characterized after its intravenous (iv) and subcutaneous (sc) administration as a racemic formulation to cattle. The (+) and (-) RBZ enantiomeric forms were recovered in plasma after iv and sc administration of the racemic RBZ formulation, using a chiral phase based HPLC method. A biexponential plasma concentration versus time curve was observed for both RBZ enantiomers following the iv treatment. Total body clearance was higher for (-) RBZ (150.4 mL/h. kg) compared with that obtained for the (+) RBZ antipode (78.1 mL/h. kg). The elimination half-life of the (-) RBZ enantiomer was shorter (T1/2beta: 2.67 h) compared with the (+) enantiomer (T1/2beta: 5.41 h). The plasma availability (expressed as AUC) was significantly higher for (+) RBZ compared with that obtained for the (-) antipode following both treatments. The enantiomeric ratio in plasma at T(0) was close to unity (50% of each enantiomer); the analysis of the concentration ratios (+) RBZ/(-) RBZ, demonstrated an increase in the proportion of (+) RBZ during the time course of the kinetics after both iv and sc treatments. The results presented herein show the enantioselective disposition kinetics of RBZ in cattle and are a further contribution to the understanding of the kinetic behaviour of these sulphoxide-containing benzimidazole anthelmintics in ruminants.

  11. Determination of gossypol enantiomer ratio in cotton plants by chiral higher-performance liquid chromatography.

    PubMed

    Cass, Quezia B; Oliveira, Regina V; De Pietro, Angela C

    2004-09-22

    A celulose tris(3,5-dimethylphenylcarbamate) coated onto APS silica (Nucleosil, particle size, 7 microm; pore size, 500 A) was used under a reversed-phase condition to measure the enantiomeric ratios of gossypol enantiomers in cottonseeds, flowers, and roots in a number of cultivars samples of different Gossipium species. While unidimensional chromatography was used for measuring the enantiomeric ratio of all the samples of G. hirsutum, G. mustelinum, and in the seeds of G. barbadense, multidimensional chromatography was necessary for the analysis of samples of roots and flowers of G. barbadense. In the latter case, an ODS Hypersil column was used in the first dimension for sample clean up, and the enantiomers were resolved on the second dimension by the chiral column. As expected, all the seed samples of G. hirsutum and G. mustelinum showed the (P)-(+)-enantiomer in excess, whereas the seeds of G. barbadense showed the (M)-(-)-enantiomer. However, (P)-(+)-gossypol was found in enantiomeric excess in three samples examined of roots and in one of flower of G. barbadense. These results are discussed in this paper.

  12. Enantiomer Specific Measurements of Current-Use Pesticides in Aquatic Systems.

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  13. #2) Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  14. Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems (#2)

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  15. TOXICITY OF FIPRONIL AND ITS ENANTIOMERS TO MARINE AND FRESHWATER NON-TARGETS

    EPA Science Inventory

    Fipronil is a phenylpyrazole insecticide used in agricultural and domestic settings for controlling various insect pests in crops, lawns, and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this ...

  16. Differential Toxicity and Accumulation of Fipronil Enantiomers in the Fathead Minnow (Pimephales promelas)

    EPA Science Inventory

    Fipronil is a chiral insecticide applied as a racemate of two enantiomers. Because of its high log Koc, fipronil will be found primarily in sediments of aquatic environments. Although a number of studies have examined toxicity in aquatic invertebrates, data on enantioselective t...

  17. Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

    ERIC Educational Resources Information Center

    Mannschreck, Albrecht; Kiesswetter, Roland; von Angerer, Erwin

    2007-01-01

    A molecule coming from outside an organism can form a ligand-receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral…

  18. Meeting in China: Differential Toxicity and Accumulation of Fipronil Enantiomers in the Fathead Minnow (Pimephales promelas)

    EPA Science Inventory

    Fipronil is a chiral insecticide applied as a racemate with two enantiomers. Because of its high log KOC, fipronil will be found primarily in sediments of aquatic environments. Although a number of studies have examined toxicity in aquatic invertebrates, data on enantioselective...

  19. ANALYSIS AND FATE OF ENANTIOMERS OF PESTICIDES AND OTHER ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    Up to 25% of pesticides and other environmental pollutants are chiral and exist as sets of mirror image isomers, or enantiomers, that usually differ in their microbiological transformation rates and toxicities. To provide for more accurate risk assessment of these chiral pollutan...

  20. Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites

    PubMed Central

    Cooper, George; Rios, Andro C.

    2016-01-01

    Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers. PMID:27247410

  1. Quantitate gossypol enantiomers in cotton flower petals and seed using capillary electrophoresis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gossypol is a compound that occurs in the cotton plant and in leaves it protects the plant from insect herbivory. The compound also occurs in the seed. In this tissue it renders the seed toxic to non-ruminant animals. However, gossypol exists as a mixture of enantiomers referred to as (+)-gossypo...

  2. Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.

    PubMed

    Zhang, Qiuyang; Yang, Wei; Zhang, Qing; Yang, Yue; Li, Junxiu; Lu, Yang; Zheng, Yi; He, Jiake; Zhao, Di; Chen, Xijing

    2015-07-01

    An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The column elute was monitored using ultraviolet detection at 214nm. The method was linear over concentration range 0.50-100μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.78-13.61 and 0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to 11.48% for (S)-oxiracetam. The method was successfully applied to a pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle dogs after oral administration. The disposition of the two enantiomers was not stereoselective and chiral inversion was not observed in beagle dogs. The pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam in beagle dogs.

  3. ACUTE AND CHRONIC EFFECTS OF FIPRONIL AND ITS ENANTIOMERS TO AQUATIC ORGANISMS

    EPA Science Inventory

    Fipronil is a phenylpyrazole insecticide used in agriculture and domestic settings for controlling various insect pests in crops, lawns and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this st...

  4. Cytotoxicity evaluation of three pairs of hexabromocyclododecane (HBCD) enantiomers on Hep G2 cell.

    PubMed

    Zhang, Xiaoling; Yang, Fangxing; Xu, Chao; Liu, Weiping; Wen, Sheng; Xu, Ying

    2008-09-01

    Hexabromocyclododecanes (HBCDs) are additive brominated flame retardants mainly used in plastics and textiles. At the present time, these compounds are found in almost all environmental and human samples. In order to evaluate the environmental safety and health risk of HBCDs, the enantiomerically pure alpha-, beta-, and gamma-HBCD were prepared using high performance liquid chromatography (HPLC) on a PM-beta-CD column and the cytotoxicities of their enantiomers were evaluated in Hep G2 cells. Results from the 3-(4,5-dimethylthioazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), resazurin reduction and lactate dehydrogenase (LDH) release assays showed a good agreement that the order of cytotoxicity was gamma-HBCDbeta-HBCD>alpha-HBCD, and that significantly lower cell viability and higher LDH release were observed in all (+)-enantiomers ((+) alpha-, (+) beta- and (+) gamma-HBCD) than the corresponding (-)-forms ((-) alpha-, (-) beta- and (-) gamma-HBCD). Additionally, the formation of reactive oxygen species (ROS) induced by these HBCD enantiomers were detected. The positive correlation between the LDH release and ROS formation demonstrated that the toxic mechanism might be mediated by oxidative damage. These results suggest that environmental and human health risks of HBCDs must be evaluated at the level of individual enantiomers.

  5. Asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. The importance of chirality in their biological evaluation.

    PubMed

    Mangas-Sánchez, Juan; Busto, Eduardo; Gotor-Fernández, Vicente; Malpartida, Francisco; Gotor, Vicente

    2011-04-01

    A simple and novel chemoenzymatic route has been applied for the first time in the synthesis of miconazole and econazole single enantiomers. Lipases and oxidoreductases have been tested in stereoselective processes; the best results were attained with oxidoreductases for the introduction of chirality in an adequate intermediate. The behaviors of a series of ketones and racemic alcohols in bioreductions and acetylation procedures, respectively, have been investigated; the best results were found with alcohol dehydrogenases A and T, which allowed the production of (R)-2-chloro-1-(2,4-dichlorophenyl)ethanol in enantiopure form under very mild reaction conditions. Final chemical modifications have been performed in order to isolate the target fungicides miconazole and econazole both as racemates and as single enantiomers. Biological evaluation of the racemates and single enantiomers has shown remarkable differences against the growth of several microorganisms; while (R)-miconazole seemed to account for most of the biological activity of racemic miconazole on all the strains tested, both enantiomers of econazole showed considerable biological activities. In this manner, (R)-econazole showed higher values against Candida krusei , while higher values were observed for (S)-econazole against Cryptococcus neoformans, Penicillium chrysogenum, and Aspergillus niger.

  6. Chromatographic resolution, characterisation and quantification of VX enantiomers in hemolysed swine blood samples.

    PubMed

    Reiter, Georg; Mikler, John; Hill, Ira; Weatherby, Kendal; Thiermann, Horst; Worek, Franz

    2008-09-15

    The present study was initiated to develop a sensitive and highly selective method for the analysis of the enantiomers of the nerve agent VX (O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate) in blood samples for toxicokinetic and therapeutic research. To achieve this goal, analytical and semi-preparative enantioseparation of VX were carried out with gas and liquid chromatography. The GC chiral stationary phase was HYDRODEX-beta-TBDAc (beta cyclodextrin), on which VX was baseline-resolved. On the chiral HPLC phase CHIRALCEL OD-H the enantiomers of VX were isolated with enantiomeric excess >99.99%. They were characterised by specific optical rotation (+/-25.8 deg ml dm(-1)g(-1) at 20 degrees C and 589 nm) and by determination of cholinesterase inhibition rate constants. For the quantitative chiral detection of VX the enantioresolution was realized on the HPLC chiral phase CHIRAL AGP. A specific procedure was developed to isolate VX from swine blood samples thereby stabilising its enantiomers. The limit of detection was 200 fg per enantiomer on column. The absolute recovery of the overall sample preparation procedure was 75%. After an intravenous and percutaneous administration of a supralethal dose of VX in anesthetised swine (+)-VX and (-)-VX could be quantified up to 720 min.

  7. cis-Bis(2,2′-bipyridine-κ2 N,N′)bis­(dimethyl sulfoxide-κO)zinc bis­(tetra­phenyl­borate) dimethyl sulfoxide monosolvate

    PubMed Central

    Tomyn, Stefania; Gumienna-Kontecka, Elżbieta; Usenko, Natalia I.; Iskenderov, Turganbay S.; Prisyazhnaya, Elena V.

    2011-01-01

    In the mononuclear title complex, [Zn(C10H8N2)2(C2H6OS)2](C24H20B)2·C2H6OS, the ZnII ion is coordinated by four N atoms of two bidentate 2,2′-bipyridine mol­ecules and by the O atoms of two cis-disposed dimethyl sulfoxide mol­ecules in a distorted octa­hedral geometry. The S atom and the methyl groups of one of the coordinated dimethyl sulfoxide mol­ecules are disordered in a 0.509 (2):0.491 (2) ratio. The crystal packing is stabilized by C—H⋯O hydrogen bonds between the dimethyl sulfoxide solvent mol­ecules and tetra­phenyl­borate anions. PMID:22199567

  8. Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A.

    PubMed

    Brock, Jonathan W C; Ames, Jennifer M; Thorpe, Suzanne R; Baynes, John W

    2007-01-15

    Chemical modification of proteins by reactive oxygen species affects protein structure, function and turnover during aging and chronic disease. Some of this damage is direct, for example by oxidation of amino acids in protein by peroxide or other reactive oxygen species, but autoxidation of ambient carbohydrates and lipids amplifies both the oxidative and chemical damage to protein and leads to formation of advanced glycoxidation and lipoxidation end-products (AGE/ALEs). In previous work, we have observed the oxidation of methionine during glycoxidation and lipoxidation reactions, and in the present work we set out to determine if methionine sulfoxide (MetSO) in protein was a more sensitive indicator of glycoxidative and lipoxidative damage than AGE/ALEs. We also investigated the sites of methionine oxidation in a model protein, ribonuclease A (RNase), in order to determine whether analysis of the site specificity of methionine oxidation in proteins could be used to indicate the source of the oxidative damage, i.e. carbohydrate or lipid. We describe here the development of an LC/MS/MS for quantification of methionine oxidation at specific sites in RNase during glycoxidation or lipoxidation by glucose or arachidonate, respectively. Glycoxidized and lipoxidized RNase were analyzed by tryptic digestion, followed by reversed phase HPLC and mass spectrometric analysis to quantify methionine and methionine sulfoxide containing peptides. We observed that: (1) compared to AGE/ALEs, methionine sulfoxide was a more sensitive biomarker of glycoxidative or lipoxidative damage to proteins; (2) regardless of oxidizable substrate, the relative rate of oxidation of methionine residues in RNase was Met29>Met30>Met13, with Met79 being resistant to oxidation; and (3) arachidonate produced a significantly greater yield of MetSO, compared to glucose. The methods developed here should be useful for assessing a protein's overall exposure to oxidative stress from a variety of sources in

  9. Three-body dissociations: The photodissociation of dimethyl sulfoxide at 193 nm

    SciTech Connect

    Blank, D.A.; North, S.W.; Stranges, D.

    1997-04-01

    When a molecule with two equivalent chemical bonds is excited above the threshold for dissociation of both bonds, how the rupture of the two bonds is temporally coupled becomes a salient question. Following absorption at 193 nm dimethyl sulfoxide (CH{sub 3}SOCH{sub 3}) contains enough energy to rupture both C-S bonds. This can happen in a stepwise (reaction 1) or concerted (reaction 2) fashion where the authors use rotation of the SOCH{sub 3} intermediate prior to dissociation to define a stepwise dissociation: (1) CH{sub 3}SOCH{sub 3} {r_arrow} 2CH{sub 3} + SO; (2a) CH{sub 3}SOCH{sub 3} {r_arrow} CH{sub 3} + SOCH{sub 3}; and (2b) SOCH{sub 3} {r_arrow} SO + CH{sub 3}. Recently, the dissociation of dimethyl sulfoxide following absorption at 193 nm was suggested to involve simultaneous cleavage of both C-S bonds on an excited electronic surface. This conclusion was inferred from laser induced fluorescence (LIF) and resonant multiphoton ionization (2+1 REMPI) measurements of the internal energy content in the CH{sub 3} and SO photoproducts and a near unity quantum yield measured for SO. Since this type of concerted three body dissociation is very interesting and a rather rare event in photodissociation dynamics, the authors chose to investigate this system using the technique of photofragment translational spectroscopy at beamline 9.0.2.1. The soft photoionization provided by the VUV undulator radiation allowed the authors to probe the SOCH{sub 3} intermediate which had not been previously observed and provided good evidence that the dissociation of dimethyl sulfoxide primarily proceeds via a two step dissociation, reaction 2.

  10. Sequential picosecond isomerizations in a photochromic ruthenium sulfoxide complex triggered by pump-repump-probe spectroscopy.

    PubMed

    King, Albert W; Jin, Yuhuan; Engle, James T; Ziegler, Christopher J; Rack, Jeffrey J

    2013-02-18

    The complex [Ru(bpy)(2)(bpSO)](PF(6))(2), where bpy is 2,2'-bipydine and bpSO is 1,2-bis(phenylsulfinyl)ethane, exhibits three distinct isomers which are accessible upon metal-to-ligand charge-transfer (MLCT) irradiation. This complex and its parent, [Ru(bpy)(2)(bpte)](PF(6))(2), where bpte is 1,2-bis(phenylthio)ethane, have been synthesized and characterized by UV-visible spectroscopy, NMR, X-ray crystallography, and femtosecond transient absorption spectroscopy. A novel method of 2-color Pump-Repump-Probe spectroscopy has been employed to investigate all three isomers of the bis-sulfoxide complex. This method allows for observation of the isomerization dynamics of sequential isomerizations of each sulfoxide from MLCT irradiation of the S,S-bonded complex to ultimately form the O,O-bonded metastable complex. One-dimensional (1-D) and two-dimensional (2-D) (COSY, NOESY, and TOCSY) (1)H NMR data show the thioether and ground state S,S-bonded sulfoxide complexes to be rigorously C(2) symmetric and are consistent with the crystal structures. Transient absorption spectroscopy reveals that the S,S to S,O isomerization occurs with an observed time constant of 56.8 (±7.4) ps. The S,O to O,O isomerization time constant was found to be 59 (±4) ps by pump-repump-probe spectroscopy. The composite S,S- to O,O-isomer quantum yield is 0.42.

  11. Stereoselective effects of mexiletine enantiomers on sodium currents and excitability characteristics of adult skeletal muscle fibers.

    PubMed

    De Luca, A; Natuzzi, F; Lentini, G; Franchini, C; Tortorella, V; Conte Camerino, D

    1995-12-01

    The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-(-) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of -100 mV to -20 mV, with an IC50 of 43.9 +/- 1 microM, whereas the corresponding S-(+) enantiomer produced the same effects at about twofold higher concentrations. A similar steroselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-(-) and S-(+) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behavior led to a significant lowering of the IC50 values with respect to the tonic block but the eudismic ratios ([IC50S-(+)]/[IC50R(-)]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h infinity), suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-(-) vs. S-(+) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential as observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-(-) isomers were more potent than the S-(+) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these

  12. Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues.

    PubMed

    Magyar, János; Rusznák, Zoltán; Harasztosi, Csaba; Körtvély, Agnes; Pacher, Pál; Bányász, Tamás; Pankucsi, Csaba; Kovács, László; Szûcs, Géza; Nánási, Péter P; Kecskeméti, Valéria

    2003-04-01

    Racemic fluoxetine is a widely used SSRI antidepressant compound having also anticonvulsant effect. In addition, it was shown that it blocked several types of voltage gated ion channels including neural and cardiac calcium channels. In the present study the effects of enantiomers of fluoxetine (R(-)-fluoxetine and S(+)-fluoxetine) were compared on neuronal and cardiac voltage-gated Ca2+ channels using the whole cell configuration of patch clamp techniques, and the anticonvulsant action of these enantiomers was also evaluated in a mouse epilepsy model. In isolated pyramidal neurons of the dorsal cochlear nucleus of the rat the effect of fluoxetine (S(+), R(-) and racemic) was studied on the Ca2+ channels by measuring peak Ba2+ current during ramp depolarizations. All forms of fluoxetine reduced the Ba2+ current of the pyramidal cells in a concentration-dependent manner, with a Kd value of 22.3+/-3.6 microM for racemic fluoxetine. This value of Kd was higher by one order of magnitude than found in cardiac myocytes with fluoxetine enantiomers (2.4+/-0.1 and 2.8+/-0.2 microM). Difference between the effects of the two enantiomers on neuronal Ba2+ current was observed only at 5 microM concentration: R(-)-fluoxetine inhibited 28+/-3% of the peak current, while S(+)-fluoxetine reduced the current by 18+/-2% (n=13, P<0.05). In voltage clamped canine ventricular cardiomyocytes both enantiomers of fluoxetine caused a reversible concentration-dependent block of the peak Ca2+ current measured at 0 mV. Significant differences between the two enantiomers in this blocking effect was observed at low concentrations only: S(+)-fluoxetine caused a higher degree of block than R(-)-fluoxetine (56.3+/-2.2% versus 49.1+/-2.2% and 95.5+/-0.9% versus 84.5+/-3.1% block with 3 and 10 microM S(+) and R(-)-fluoxetine, respectively, P<0.05, n=5). Studied in current clamp mode, micromolar concentrations of fluoxetine shortened action potential duration of isolated ventricular cells, while higher

  13. Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

    PubMed

    Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

    2015-02-01

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.

  14. Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing

    PubMed Central

    Mi, Hongfei; Wang, Dai; Xue, Yunxin; Zhang, Zhi; Hong, Yuzhi; Drlica, Karl

    2016-01-01

    The contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treating Escherichia coli with dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays. PMID:27246776

  15. Crystal structure of hexa-kis-(dimethyl sulfoxide-κO)manganese(II) diiodide.

    PubMed

    Glatz, Mathias; Schroffenegger, Martina; Weil, Matthias; Kirchner, Karl

    2016-07-01

    The asymmetric unit of the title salt, [Mn(C2H6OS)6]I2, consists of one Mn(II) ion, six O-bound dimethyl sulfoxide (DMSO) ligands and two I(-) counter-anions. The isolated complex cations have an octa-hedral configuration and are grouped in hexa-gonally arranged rows extending parallel to [100]. The two I(-) anions are located between the rows and are linked to the cations through two weak C-H⋯I inter-actions.

  16. Genetic Analysis of the System that Reduces Biotin-d-Sulfoxide in Escherichia coli

    PubMed Central

    Dykhuizen, Daniel

    1973-01-01

    Four genes of Escherichia coli whose products are needed to reduce biotin-d-sulfoxide to biotin have been mapped: bisA next to chlA, bisB next to chlE, bisC linked to xyl, and bisD next to chlG. A defective λ transducing phage, λdbis5, which carries all the bacterial genes between the λ attachment site and chlE, was isolated and shown to have lost the phage genes from int through Q. PMID:4579877

  17. Di-μ-chlorido-bis-[chloridobis(dimethyl sulfoxide)dioxidouranium(VI)].

    PubMed

    Takao, Koichiro; Ikeda, Yasuhisa

    2007-12-06

    In the crystal structure of the title compound, [U(2)Cl(4)O(4)(C(2)H(6)OS)(4)], the compound has a centrosymmetric dimeric structure bridged by two chloride anions. Each U(VI) atom is seven-coordinate in a penta-gonal-bipyramidal geometry. In the equatorial plane of the uranyl unit there are two O atoms from non-adjacent dimethyl sulfoxides and three chloride ions (of which two chlorides are bridging). The compound is of inter-est as an anhydrous starting material of the uran-yl(VI) ion.

  18. Di-μ-chlorido-bis­[chloridobis(dimethyl sulfoxide)dioxidouranium(VI)

    PubMed Central

    Takao, Koichiro; Ikeda, Yasuhisa

    2008-01-01

    In the crystal structure of the title compound, [U2Cl4O4(C2H6OS)4], the compound has a centrosymmetric dimeric structure bridged by two chloride anions. Each UVI atom is seven-coordinate in a penta­gonal-bipyramidal geometry. In the equatorial plane of the uranyl unit there are two O atoms from non-adjacent dimethyl sulfoxides and three chloride ions (of which two chlorides are bridging). The compound is of inter­est as an anhydrous starting material of the uran­yl(VI) ion. PMID:21200466

  19. An Uncharged Oxetanyl Sulfoxide as a Covalent Modifier for Improving Aqueous Solubility

    PubMed Central

    2014-01-01

    Low aqueous solubility is a common challenge in drug discovery and development and can lead to inconclusive biological assay results. Attaching small, polar groups that do not interfere with the bioactivity of the pharmacophore often improves solubility, but there is a dearth of viable neutral moieties available for this purpose. We have modified several poorly soluble drugs or drug candidates with the oxetanyl sulfoxide moiety of the DMSO analog MMS-350 and noted in most cases a moderate to large improvement of aqueous solubility. Furthermore, the membrane permeability of a test sample was enhanced compared to the parent compound. PMID:25147611

  20. Effect of dimethyl sulfoxide addition on ultrasonic degradation of methylene blue

    NASA Astrophysics Data System (ADS)

    Shimakage, Kaho; Kobayashi, Daisuke; Naya, Masakazu; Matsumoto, Hideyuki; Shimada, Yuichiro; Otake, Katsuto; Shono, Atsushi

    2016-07-01

    The ultrasonic degradation of methylene blue was carried out in the absence and presence of dimethyl sulfoxide (DMSO) as a radical scavenger for various frequencies, and the effects of DMSO addition on the degradation rate constant estimated by assuming first-order kinetics were investigated. The degradation reaction rate decreased with DMSO addition, and hydroxyl radicals were observed to play important roles in the degradation of methylene blue. However, the degradation reaction did not stop with DMSO addition, and the degradation rate constant in the presence of DMSO was not affected by ultrasonic frequency.

  1. Cyclic sulfoxides-garlicnins K1, K2, and H1-extracted from Allium sativum.

    PubMed

    Nohara, Toshihiro; Fujiwara, Yukio; Komota, Yusuke; Kondo, Yoshihiko; Saku, Taiki; Yamaguchi, Koki; Komohara, Yoshihiro; Takeya, Motohiro

    2015-01-01

    Newly identified cyclic sulfoxides-garlicnins K1 (1), K2 (2), and H1 (3)-were isolated from the acetone extracts of the bulbs of garlic, Allium sativum. Garlicnin H1 (3) demonstrated potential to suppress tumor cell proliferation by regulating macrophage activation. The structures of garlicnins K1 and K2, 3,4-dimethyl-5-allyl-tetrahydrothiophen-2-one-S-oxides, and the structure of garlicnin H1, 3-carboxy-3-hydroxy-4-methyl-5-allylsulfoxide-tetrahydrothiophen-2-(ethane-1,2-diol)-S-oxide were characterized by spectroscopic analysis.

  2. Behavioral Responses of Plum Curculio (Coleoptera: Curculionidae) to Different Enantiomer Concentrations and Blends of the Synthetic Aggregation Pheromone Grandisoic Acid.

    PubMed

    Hock, Virginia; Chouinard, Gérald; Lucas, Éric; Cormier, Daniel; Leskey, Tracy C; Wright, Starker E; Zhang, Aijun; Pichette, André

    2015-04-01

    The plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), is an important pest of fruit in North America. Males produce an aggregation pheromone (grandisoic acid) that attracts both sexes of the northern univoltine and the southern multivoltine strains. Grandisoic acid ((1R,2S)-1-methyl-2-(1-methylethenyl)-cyclobutaneacetic acid) is a chiral molecule containing one chiral center. A synthetic racemic mixture will contain two optical isomers that are mirror images of each other with equal amounts of (+)- and (-)-enantiomeric isomers. Male plum curculio only produce the (+) enantiomer. Some enantiomers can have antagonistic effects on the attraction of weevils to pheromones. An understanding of the effect of both enantiomers on the behaviour of plum curculio is needed to develop more efficient trap baits. Behavioural bioassays were conducted in a dual-choice still-air vertical olfactometer using a quantity of 1.5 ml of both (+) and (-) synthetic enantiomers and the racemic mixture of grandisoic acid with live female responders to determine which concentration and enantiomeric purity is the most attractive and if there is an antagonistic effect of the unnatural (-) enantiomer. Results indicated that plum curculio were attracted to low concentrations of the (+) enantiomer at 72% enantiomeric excess, but that strains were attracted to different concentrations of the (+) enantiomer (2×10(-7) mg/ml for univoltine, 2×10(-9) mg/ml for multivoltine).

  3. A quantification method for determination of racemate praziquantel and R-enantiomer in rat plasma for comparison of their pharmacokinetics.

    PubMed

    Zhang, Danlu; Wang, Haina; Ji, Jianbo; Nie, Lei; Sun, Dequn

    2017-03-24

    Praziquantel is the drug of first choice for the control and treatment of all forms of schistosomiasis. Praziquantel is administered as a racemate, including R-enantiomer and S-enantiomer. Among them, R-enantiomer has main contribution to schistosomicidal activity. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry was established and validated to determine the concentration of racemate praziquantel and R-enantiomer in rat plasma after oral administration. Chromatographic separation was performed on an Agilent Zorbax SB-C18 column. An entire run time for chromatographic separation was no more than 5min. The present method for analytes manifested that high sensitivity (the lower limit of quantification was 3.0ng/mL), satisfactory accuracy (relative error ≤±15%) and precision (relative standard deviation ≤15%) were achieved. There was no obvious matrix effect found. The average recoveries of racemate praziquantel and R-enantiomer were both above 85%. Then, the developed method had a successful application to comparative pharmacokinetic study of racemate praziquantel and R-enantiomer. Meanwhile, the differences in their pharmacokinetic parameters were compared and analyzed. The present quantification method and comparative pharmacokinetic study would provide a useful reference for the drug development of enantiopure schistosomicidal R-enantiomer as a replacement of racemate praziquantel for treatment of schistosomiasis.

  4. Synergism between Enantiomers Creates Species-Specific Pheromone Blends and Minimizes Cross-Attraction for Two Species of Cerambycid Beetles.

    PubMed

    Meier, Linnea R; Zou, Yunfan; Millar, Jocelyn G; Mongold-Diers, Judith A; Hanks, Lawrence M

    2016-11-01

    Research over the last decade has revealed extensive parsimony among pheromones within the large insect family Cerambycidae, with males of many species producing the same, or very similar aggregation pheromones. Among some species in the subfamily Cerambycinae, interspecific attraction is minimized by temporal segregation, and/or by minor pheromone components that synergize attraction of conspecifics or inhibit attraction of heterospecifics. Less is known about pheromone-based mechanisms of reproductive isolation among species in the largest subfamily, the Lamiinae. Here, we present evidence that the pheromone systems of two sympatric lamiine species consist of synergistic blends of enantiomers of (E)-6,10-dimethyl-5,9-undecadien-2-ol (fuscumol) and the structurally related (E)-6,10-dimethyl-5,9-undecadien-2-yl acetate (fuscumol acetate), as a mechanism by which species-specific blends of pheromone components can minimize interspecific attraction. Male Astylidius parvus (LeConte) were found to produce (R)- and (S)-fuscumol + (R)-fuscumol acetate + geranylacetone, whereas males of Lepturges angulatus (LeConte) produced (R)- and (S)-fuscumol acetate + geranylacetone. Field experiments confirmed that adult beetles were attracted only by their species-specific blend of the enantiomers of fuscumol and fuscumol acetate, respectively, and not to the individual enantiomers. Because other lamiine species are known to produce single enantiomers or blends of enantiomers of fuscumol and/or fuscumol acetate, synergism between enantiomers, or inhibition by enantiomers, may be a widespread mechanism for forming species-specific pheromone blends in this subfamily.

  5. Applications of nuclear magnetic resonance spectroscopy for the understanding of enantiomer separation mechanisms in capillary electrophoresis.

    PubMed

    Salgado, Antonio; Chankvetadze, Bezhan

    2016-10-07

    This review deals with the applications of nuclear magnetic resonance (NMR) spectroscopy to understand the mechanisms of chiral separation in capillary electrophoresis (CE). It is accepted that changes observed in the separation process, including the reversal of enantiomer migration order (EMO), can be caused by subtle modifications in the molecular recognition mechanisms between enantiomer and chiral selector. These modifications may imply minor structural differences in those selector-selectand complexes that arise from the above mentioned interactions. Therefore, it is mandatory to understand the fine intermolecular interactions between analytes and chiral selectors. In other words, it is necessary to know in detail the structures of the complexes formed by the enantiomer (selectand) and the selector. Any differences in the structures of these complexes arising from either enantiomer should be detected, so that enantiomeric bias in the separation process could be explained. As to the nature of these interactions, those have been extensively reviewed, and it is not intended to be discussed here. These interactions contemplate ionic, ion-dipole and dipole-dipole interactions, hydrogen bonding, van der Waals forces, π-π stacking, steric and hydrophobic interactions. The main subject of this review is to describe how NMR spectroscopy helps to gain insight into the non-covalent intermolecular interactions between selector and selectand that lead to enantiomer separation by CE. Examples in which diastereomeric species are created by covalent (irreversible) derivatization will not be considered here. This review is structured upon the different structural classes of chiral selectors employed in CE, in which NMR spectroscopy has made substantial contributions to rationalize the observed enantioseparations. Cases in which other techniques complement NMR spectroscopic data are also mentioned.

  6. Modulation of transcription factor NF-κB by enantiomers of the nonsteroidal drug ibuprofen

    PubMed Central

    Scheuren, Nicole; Bang, Holger; Münster, Tino; Brune, Kay; Pahl, Andreas

    1998-01-01

    The nonsteroidal drug ibuprofen exists as an R(−)- and S(+)-enantiomer. Only the S(+)-enantiomer is an effective cyclo-oxygenase inhibitor, while the R(−)-enantiomer is inactive in this respect. Thus the molecular mechanism by which R(−)-ibuprofen exerts its anti-inflammatory and antinociceptive effects remains unknown. In this study the effects of the enantiomers of ibuprofen on modulation of transcription factors have been examined with electrophoretic mobility-shift assay (EMSA), transient transfection experiments, confocal immunofluorescence and nuclear import experiments, to determine their selectivity and potency as inhibitors of the activation of transcription factor nuclear factor-κB (NF-κB). R(−)-ibuprofen (IC50: 121.8 μM) as well as the S(+)-enantiomer (IC50: 61.7 μM) inhibited the activation of NF-κB in response to T-cell stimulation. The effect of ibuprofen was specific because, at concentrations up to 10 mM, ibuprofen did not affect the heat shock transcription factor (HSF) and the activation of NF-κB by prostaglandin E2 (PGE2). Very high concentrations of ibuprofen (20 mM) did not prevent NF-κB binding to DNA in vitro. Immunofluorescence and nuclear import experiments indicate that the site of ibuprofen action appeared to be upstream of the dissociation of the NF-κB-IκB-complex. Our data raise the possibility that R(−)-ibuprofen exerts some of its effects by inhibition of NF-κB activation. PMID:9517383

  7. Stereoselectivity of chiral drug transport: a focus on enantiomer-transporter interaction.

    PubMed

    Zhou, Quan; Yu, Lu-Shan; Zeng, Su

    2014-08-01

    Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enantiomer-transporter interaction. In recent years, the experimental research within this field showed good momentum. Herein, an up-to-date review on this topic was presented. Breast Cancer Resistance Protein (BCRP), Multidrug Resistance Proteins (MRP), P-glycoprotein (P-gp), Organic Anion Transporters (OATs), Organic Anion Transporting Polypeptides (OATPs), Organic Cation Transporters (OCTs), Peptide Transport Proteins (PepTs), Human Proton-Coupled Folate Transporter (PCFT) and Multidrug and Toxic Extrusion Proteins (MATEs), have been reported to exhibit either positive or negative enantio-selective substrate recognition. The approaches utilized to study chirality in enantiomer-transporter interaction include inhibition experiments of specific transporters in cell models (e.g. Caco-2 cells), transport study using drug resistance cell lines or transgenic cell lines expressing transporters in wild type or variant, the use of transporter knockout mice, pharmacokinetics association of single nucleotide polymorphism in transporters, pharmacokinetic interaction study of racemate in the presence of specific transporter inhibitor or inducer, molecule cellular membrane affinity chromatography and pharmacophore modeling. Enantiomer-enantiomer interactions exist in chiral transport. The strength and/or enantiomeric preference of stereoselectivity may be species or tissue-specific, concentration-dependent and transporter family member-dependent. Modulation of specific drug transporter by pure enantiomers might exhibit opposite stereoselectivity. Further studies with integrated approaches will open up new horizons in stereochemistry of pharmacokinetics.

  8. Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta).

    PubMed

    Saunders, David; Vanachayangkul, Pattaraporn; Imerbsin, Rawiwan; Khemawoot, Phisit; Siripokasupkul, Raveewan; Tekwani, Babu L; Sampath, Aruna; Nanayakkara, N P Dhammika; Ohrt, Colin; Lanteri, Charlotte; Gettyacamin, Montip; Teja-Isavadharm, Paktiya; Walker, Larry

    2014-12-01

    Primaquine (PQ) remains the sole available drug to prevent relapse of Plasmodium vivax malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to Plasmodium cynomolgi-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (-)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (-)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (-)-PQ at 4.5 mg/kg. (-)-PQ in combination with chloroquine was successful in preventing P. cynomolgi disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (-)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers.

  9. A QSPR study on the solvent-induced frequency shifts of acetone and dimethyl sulfoxide in organic solvents

    NASA Astrophysics Data System (ADS)

    Ou, Yu Heng; Chang, Chia Ming; Chen, Ying Shao

    2016-06-01

    In this study, solvent-induced frequency shifts (SIFS) in the infrared spectrum of acetone and dimethyl sulfoxide in organic solvents were investigated by using four types of quantum-chemical reactivity descriptors. The results showed that the SIFS of acetone is mainly affected by the electron-acceptance chemical potential and the maximum nucleophilic condensed local softness of organic solvents, which represent the electron flow and the polarization between acetone and solvent molecules. On the other hand, the SIFS of dimethyl sulfoxide changes with the maximum positive charge of hydrogen atom and the inverse of apolar surface area of solvent molecules, showing that the electrostatic and hydrophilic interactions are main mechanisms between dimethyl sulfoxide and solvent molecules. The introduction of the four-element theory model-based quantitative structure-property relationship approach improved the assessing quality and provided a basis for interpreting the solute-solvent interactions.

  10. A QSPR study on the solvent-induced frequency shifts of acetone and dimethyl sulfoxide in organic solvents.

    PubMed

    Ou, Yu Heng; Chang, Chia Ming; Chen, Ying Shao

    2016-06-05

    In this study, solvent-induced frequency shifts (SIFS) in the infrared spectrum of acetone and dimethyl sulfoxide in organic solvents were investigated by using four types of quantum-chemical reactivity descriptors. The results showed that the SIFS of acetone is mainly affected by the electron-acceptance chemical potential and the maximum nucleophilic condensed local softness of organic solvents, which represent the electron flow and the polarization between acetone and solvent molecules. On the other hand, the SIFS of dimethyl sulfoxide changes with the maximum positive charge of hydrogen atom and the inverse of apolar surface area of solvent molecules, showing that the electrostatic and hydrophilic interactions are main mechanisms between dimethyl sulfoxide and solvent molecules. The introduction of the four-element theory model-based quantitative structure-property relationship approach improved the assessing quality and provided a basis for interpreting the solute-solvent interactions.

  11. An antioxidant response is involved in resistance of Giardia duodenalis to albendazole

    PubMed Central

    Argüello-García, Raúl; Cruz-Soto, Maricela; González-Trejo, Rolando; Paz-Maldonado, Luz María T.; Bazán-Tejeda, M. Luisa; Mendoza-Hernández, Guillermo; Ortega-Pierres, Guadalupe

    2015-01-01

    Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ. PMID

  12. Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis

    PubMed Central

    Martínez-Espinosa, Rodrigo; Argüello-García, Raúl; Saavedra, Emma; Ortega-Pierres, Guadalupe

    2015-01-01

    The control of Giardia duodenalis infections is carried out mainly by drugs, among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of ABZ usually involves binding to β-tubulin, it has been suggested that oxidative stress may also play a role in its parasiticidal mechanism. In this work the effect of ABZ in Giardia clones that are susceptible or resistant to different concentrations (1.35, 8, and 250 μM) of this drug was analyzed. Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this was associated with a decrease in growth that was alleviated by cysteine supplementation. Remarkably, ABZ-resistant clones exhibited partial cross-resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated parasites did not show significant differences as compared to untreated parasites; however, ABZ induced the formation of 8OHdG adducts and DNA degradation, indicating nucleic acid oxidative damage. This was supported by observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites treated with 250 μM ABZ. Flow cytometry analysis showed that ABZ partially arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on the parasite surface, an event related to apoptosis. All together these data suggest that ROS induced by ABZ affect Giardia genetic material through oxidative stress mechanisms and subsequent induction of apoptotic-like events. PMID:26300866

  13. An antioxidant response is involved in resistance of Giardia duodenalis to albendazole.

    PubMed

    Argüello-García, Raúl; Cruz-Soto, Maricela; González-Trejo, Rolando; Paz-Maldonado, Luz María T; Bazán-Tejeda, M Luisa; Mendoza-Hernández, Guillermo; Ortega-Pierres, Guadalupe

    2015-01-01

    Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ.

  14. Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

    PubMed

    Ismail, M M; Jayakody, R L; Weil, G J; Nirmalan, N; Jayasinghe, K S; Abeyewickrema, W; Rezvi Sheriff, M H; Rajaratnam, H N; Amarasekera, N; de Silva, D C; Michalski, M L; Dissanaike, A S

    1998-01-01

    In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

  15. Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

    PubMed

    Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun

    2016-03-01

    Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.

  16. Efficacy of co-administration of albendazole and diethylcarbamazine against geohelminthiases: a study from South India.

    PubMed

    Mani, T R; Rajendran, R; Munirathinam, A; Sunish, I P; Md Abdullah, S; Augustin, D J; Satyanarayana, K

    2002-06-01

    The efficacy of single-dose combination drug therapy with diethylcarbamazine (DEC) plus albendazole (ALB), and single-drug therapy with DEC alone against geohelminths was compared as part of a mass drug administration (MDA) for elimination of filariasis. This study was conducted in two blocks of Villupuram District of Tamil Nadu State, India, covering a population of 321 000 including about 100 000 children 1-15 years of age. Prevalence and intensity of geohelminth infection were determined by the Kato-Katz technique immediately before and 3 weeks after the MDA. A pre-treatment cross-sectional survey was undertaken in 18 statistically selected villages out of 204 villages, including 646 school children. About 60% were infected with one or more geohelminths. The overall prevalence rates were 53.9%, 12.4% and 5.7% for Ascaris lumbricoides, hookworms and Trichuris trichiura, respectively. Combination therapy (DEC + ALB) produced a cure rate of 74.3% and an egg reduction rate of 97.3% for geohelminths, which were higher than the corresponding rates (30.4% and 79.0%) observed in the single drug therapy arm with DEC alone. The odds of cure with combination therapy were significantly higher for roundworm (5.3 times) and hookworms (3.5 times), then odds of cure with DEC alone. Both therapies were equally effective against trichuriasis, recording cure rates >77% and egg reduction rates >83%. In combination therapy, 53.5% of the children noticed expulsion of worms after MDA, while in single drug therapy only 20.9% did. Our study indicated that MDA of combination therapy was operationally feasible at the community level, and it may secure higher community compliance because of its perceived benefits and enhanced efficacy against geohelminths than single-drug therapy.

  17. Ribbons of hydrogen-bonded rings in the 1:2 complex of pyromellitic acid and dimethyl sulfoxide.

    PubMed

    Jin, Zhi Min; Pan, Yuan Jian; Shen, Liang; Li, Mei Chao; Hu, Mao Lin

    2003-04-01

    In the title complex, pyromellitic acid-dimethyl sulfoxide (1/2), C(10)H(6)O(8).2C(2)H(6)OS, molecules of pyromellitic acid (1,2,4,5-benzenetetracarboxylic acid) and dimethyl sulfoxide, the latter being well ordered, are linked to each other by O-H.O hydrogen bonds. The formula unit displays crystallographic inversion symmetry. The packing consists of ribbons of hydrogen-bonded rings that can be described by graph set C(2)(1)(10)R(4)(2)(18).

  18. A general and expeditious one-pot synthesis of sulfoxides in high optical purity from norephedrine-derived sulfamidites.

    PubMed

    García Ruano, José L; Alemparte, Carlos; Aranda, M Teresa; Zarzuelo, María M

    2003-01-09

    A general and simple procedure for preparing any kind of enantiomerically enriched sulfoxide starting from norephedrine-derived N-benzyloxycarbonylsulfamidite 3a is reported. After one-pot reaction of 3a with RMgX, HBF(4), and R'MgX, a variety of sulfoxides 6 are obtained in ee usually higher than 93% and isolated yields ranging between 50 and 78%. The obtained configuration is tunable by simply electing the order of the addition of the reagents. [reaction--see text

  19. Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity

    PubMed Central

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M.; Bortolato, Marco

    2015-01-01

    Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous SNP that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood posttranslational mechanisms. One posttranslational modification is methionine sulfoxide, which can be reduced by the methionine sulfoxide reductase (Msr) A and B enzymes. We used recombinant COMT proteins (Val/Met108) and mice (wild-type (WT) and MsrA knockout) to determine the effect of methionine oxidation on COMT activity and COMT interaction with Msr, through a combination of enzymatic activity and Western blot assays. Recombinant COMT activity is positively regulated by MsrA, especially under oxidative conditions, while brains of MsrA knockout mice exhibited lower COMT activity (as compared with their WT counterparts). These results suggest that COMT activity may be reduced by methionine oxidation, and point to Msr as a key molecular determinant for the modulation of COMT activity in the brain. The role of Msr in modulating cognitive functions in healthy individuals and schizophrenia patients is yet to be determined. PMID:24735585

  20. Dimethyl sulfoxide can initiate cell divisions of arrested callus protoplasts by promoting cortical microtuble assembly

    SciTech Connect

    Hahne, G.; Hoffmann, F.

    1984-09-01

    A serious problem in the technology of plant cell culture is that isolated protoplasts from many species are reluctant to divide. We have succeeded in inducing consecutive divisions in a naturally arrested system i.e., protoplasts from a hibiscus cell line, which do not divide under standard conditions and in an artificially arrested system i.e., colchicine-inhibited callus protoplasts of Nicotiana glutinosa, which do readily divide in the absence of colchicine. In both cases, the reinstallation of a net of cortical microtubules, which had been affected either by colchicine or by the protoplast isolation procedure, resulted in continuous divisions of the formerly arrested protoplasts. Several compounds known to support microtubule assembly in vitro were tested for their ability to promote microtubule assembly in vivo. Best results were obtained by addition of dimethyl sulfoxide to the culture medium. Unlimited amounts of callus could be produced with the dimethyl sulfoxide method from protoplasts which never developed a single callus in control experiments. 30 references, 3 figures.

  1. Evidence for participation of the methionine sulfoxide reductase repair system in plant seed longevity

    PubMed Central

    Châtelain, Emilie; Satour, Pascale; Laugier, Edith; Ly Vu, Benoit; Payet, Nicole; Rey, Pascal; Montrichard, Françoise

    2013-01-01

    Seeds are in a natural oxidative context leading to protein oxidation. Although inevitable for proper progression from maturation to germination, protein oxidation at high levels is detrimental and associated with seed aging. Oxidation of methionine to methionine sulfoxide is a common form of damage observed during aging in all organisms. This damage is reversible through the action of methionine sulfoxide reductases (MSRs), which play key roles in lifespan control in yeast and animal cells. To investigate the relationship between MSR capacity and longevity in plant seeds, we first used two Medicago truncatula genotypes with contrasting seed quality. After characterizing the MSR family in this species, we analyzed gene expression and enzymatic activity in immature and mature seeds exhibiting distinct quality levels. We found a very strong correlation between the initial MSR capacities in different lots of mature seeds of the two genotypes and the time to a drop in viability to 50% after controlled deterioration. We then analyzed seed longevity in Arabidopsis thaliana lines, in which MSR gene expression has been genetically altered, and observed a positive correlation between MSR capacity and longevity in these seeds as well. Based on our data, we propose that the MSR repair system plays a decisive role in the establishment and preservation of longevity in plant seeds. PMID:23401556

  2. Evidence for the dimerization-mediated catalysis of methionine sulfoxide reductase A from Clostridium oremlandii.

    PubMed

    Lee, Eun Hye; Lee, Kitaik; Kwak, Geun-Hee; Park, Yeon Seung; Lee, Kong-Joo; Hwang, Kwang Yeon; Kim, Hwa-Young

    2015-01-01

    Clostridium oremlandii MsrA (CoMsrA) is a natively selenocysteine-containing methionine-S-sulfoxide reductase and classified into a 1-Cys type MsrA. CoMsrA exists as a monomer in solution. Herein, we report evidence that CoMsrA can undergo homodimerization during catalysis. The monomeric CoMsrA dimerizes in the presence of its substrate methionine sulfoxide via an intermolecular disulfide bond between catalytic Cys16 residues. The dimeric CoMsrA is resolved by the reductant glutaredoxin, suggesting the relevance of dimerization in catalysis. The dimerization reaction occurs in a concentration- and time-dependent manner. In addition, the occurrence of homodimer formation in the native selenoprotein CoMsrA is confirmed. We also determine the crystal structure of the dimeric CoMsrA, having the dimer interface around the two catalytic Cys16 residues. A central cone-shaped hole is present in the surface model of dimeric structure, and the two Cys16 residues constitute the base of the hole. Collectively, our biochemical and structural analyses suggest a novel dimerization-mediated mechanism for CoMsrA catalysis that is additionally involved in CoMsrA regeneration by glutaredoxin.

  3. Ultrafast spectroscopy and structural characterization of a photochromic isomerizing ruthenium bis-sulfoxide complex.

    PubMed

    King, Albert W; Malizia, Jason P; Engle, James T; Ziegler, Christopher J; Rack, Jeffrey J

    2014-12-21

    Irradiation of [Ru(bpy)2(bpSOp)](PF6)2 (where bpy is 2,2'-bipyridine and bpSOp is 1,3-bis(phenylsulfinyl)propane) results in the formation of two new isomers, namely the S,O- and O,O-bonded species. The crystal structure of the bis-thioether and bis-sulfoxide complexes are reported. NMR spectroscopy of the bis-thioether complex in solution is consistent with the molecular structure determined by diffraction methods. Further, NMR spectroscopy of the bis-sulfoxide complex reveals two conformers in solution, one that is consistent with the solid state structure and a second conformer showing distortion in the aliphatic portion of the chelate ring. Time-resolved visible absorption spectroscopy reveals isomerization time constants of 91 ps in dichloroethane (DCE) and 229 ps in propylene carbonate (PC). Aggregate isomerization quantum yields of 0.57 and 0.42 have been determined in DCE and in PC, respectively. The kinetics of the thermal reversion from the O,O- to S,O-bonded isomer are strongly solvent dependent, occurring with rates of 2.41 × 10(-3) and 4.39 × 10(-5) s(-1) in DCE, and 4.68 × 10(-4) and 9.79 × 10(-6) s(-1) in PC. The two kinetic components are assigned to the two isomers identified in solution.

  4. Evidence for participation of the methionine sulfoxide reductase repair system in plant seed longevity.

    PubMed

    Châtelain, Emilie; Satour, Pascale; Laugier, Edith; Ly Vu, Benoit; Payet, Nicole; Rey, Pascal; Montrichard, Françoise

    2013-02-26

    Seeds are in a natural oxidative context leading to protein oxidation. Although inevitable for proper progression from maturation to germination, protein oxidation at high levels is detrimental and associated with seed aging. Oxidation of methionine to methionine sulfoxide is a common form of damage observed during aging in all organisms. This damage is reversible through the action of methionine sulfoxide reductases (MSRs), which play key roles in lifespan control in yeast and animal cells. To investigate the relationship between MSR capacity and longevity in plant seeds, we first used two Medicago truncatula genotypes with contrasting seed quality. After characterizing the MSR family in this species, we analyzed gene expression and enzymatic activity in immature and mature seeds exhibiting distinct quality levels. We found a very strong correlation between the initial MSR capacities in different lots of mature seeds of the two genotypes and the time to a drop in viability to 50% after controlled deterioration. We then analyzed seed longevity in Arabidopsis thaliana lines, in which MSR gene expression has been genetically altered, and observed a positive correlation between MSR capacity and longevity in these seeds as well. Based on our data, we propose that the MSR repair system plays a decisive role in the establishment and preservation of longevity in plant seeds.

  5. Apratoxin H and Apratoxin A Sulfoxide from the Red Sea Cyanobacterium Moorea producens

    PubMed Central

    Thornburg, Christopher C.; Cowley, Elise S.; Sikorska, Justyna; Shaala, Lamiaa A.; Ishmael, Jane E.; Youssef, Diaa T.A.; McPhail, Kerry L.

    2014-01-01

    Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues, apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A-C, lyngbyabellin B and hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relationships in the apratoxin series. Phylogenetic analysis of the apratoxin-producing cyanobacterial strains belonging to the genus Moorea, coupled with the recently annotated apratoxin biosynthetic pathway, supports the notion that apratoxin production and structural diversity may be specific to their geographical niche. PMID:24016099

  6. APPLICATION OF CYCLODEXTRIN-MODIFIED MICELLAR ELECTRONKINETIC CHROMATOGRAPHY TO THE SEPARATIONS OF SELECTED NEUTRAL PESTICIDES AND THEIR ENANTIOMERS

    EPA Science Inventory

    The environmental chemistry of chiral pesticides is receiving increased attention - enantiomeric ratios are being measured and enantioselective degradation processes are being reported. The requisite analysis involves separation of the various enantiomers. Mixtures of three class...

  7. Bioanalysis of the enantiomers of (+/-)-sarin using automated thermal cold-trap injection combined with two-dimensional gas chromatography.

    PubMed

    Spruit, H E; Trap, H C; Langenberg, J P; Benschop, H P

    2001-01-01

    A fully automated multidimensional gas chromatographic system with thermal desorption injection and alkali flame detection was developed for analysis of the enantiomers of the nerve agent (+/-)-sarin. The chiral stationary phase was CP Cyclodex B on which the sarin enantiomers were completely resolved. The absolute detection limit was 2.5 pg per enantiomer. The method is intended to be used for the analysis of the sarin enantiomers in biological samples. For this purpose, sarin was isolated from guinea pig blood via solid-phase extraction. Deuterated sarin was used as internal standard. Stabilization of sarin in the blood sample by acidification and addition of an excess of a competitive organophosphorus compound (neopentyl sarin) appeared to be essential. The absolute recovery of the extraction procedure was 60%, whereas the recovery relative to the internal standard was 100%.

  8. Gas-chromatographic determination of nanogram amounts of enantiomers of nortilidine, a main metabolite of tilidine, in biological specimens.

    PubMed

    Hengy, H; Vollmer, K O; Gladigau, V

    1978-04-01

    We report a specific and sensitive method for determination of the individual optical isomers of nortilidine, a main metabolite of tilidine, with the aid of a nitrogen-sensitive detector. With N-trifluoroacetyl-L-leucyl chloride as chiral reagent, the diastereomeric derivatives of the nortilidine enantiomers could be separated and quantified in the nanogram range. Under these conditions, the enantiomers of bisnortilidine, another main metabolite of tilidine, were also separated. Investigations in rats with the enantiomers of tilidine and nortilidine indicated that no racemization occurs during N-demethylation in the organism. After oral and intravenous administration of 50 mg of tilidine.HCI to a human volunteer, identical concentrations of nortilidine enantiomers were found in the plasma.

  9. About the role of enantioselective selector-selectand interactions and the mobilities of diastereomeric associates in enantiomer separations using CE.

    PubMed

    Lomsadze, Ketevan; Martínez-Girón, Ana B; Castro-Puyana, María; Chankvetadze, Lali; Crego, Antonio L; Salgado, Antonio; Marina, María Luisa; Chankvetadze, Bezhan

    2009-08-01

    It is generally accepted that the selective binding of enantiomers of the chiral analyte to a chiral selector is necessary for enantioseparations in CE, whereas the role of mobility differences between the temporary diastereomeric associates formed between the enantiomers and the chiral selector has been commonly neglected. One of the authors of this study suggested in 1997 that the mobility difference between the diastereomeric associates of two enantiomers with the chiral selector may be solely responsible for a separation of enantiomers in CE and enantioselective selector-selectand binding may be not necessarily required. Several indirect confirmations of this hypothesis have been described in the literature within the last few years but a dedicated study proving this concept has not been published yet. The present data obtained for the two chiral antimycotic drugs ketoconazole and terconazole by CE and NMR spectroscopy unequivocally support this concept.

  10. Synthesis and odor description of both enantiomers of methyl 4,5-didehydrojasmonate, a component of jasmin absolute.

    PubMed

    Asamitsu, Yuko; Nakamura, Yoko; Ueda, Minoru; Kuwahara, Shigefumi; Kiyota, Hiromasa

    2006-06-01

    Synthesis of both enantiomers of methyl 4,5-didehydrojasmonate (1, Delta(4,5)-MJA; >99.8% ee), a constituent of jasmin absolute, established the absolute configuration of the natural product, and their odor quality was evaluated. The fragrance of the natural (3S,7R)-enantiomer (a fresh natural, sweet floral fruity odor, reminiscent of Jasmin and Ylang Ylang flower, more intensive and tenacious) was superior to that of the unnatural (3R,7S)-enantiomer (a floral green odor with slight metallic green aspect, less intensive than the natural form) and the racemate (green-floral note, having weak and less volume than methyl jasmonate). Odor difference between natural and unnatural enantiomers of methyl jasmonate (2) is also reported.

  11. ENANTIOMER FRACTIONS OF CHLORDANE COMPOUNDS IN SEDIMENT SAMPLES FROM U.S. GEOLOGICAL SURVEY SITES IN LAKES, RIVERS, AND RESERVOIRS

    EPA Science Inventory

    More than 500 important environmental contaminants are chiral (having structures that are nonsuperimposible mirror images). Although enantiomer pairs have identical physical-chemical properties, their toxicity, biodegradation, and environmental fate often are different. Cyclo...

  12. Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole, a class II compound.

    PubMed

    Piccirilli, Gisela N; García, Agustina; Leonardi, Darío; Mamprin, María E; Bolmaro, Raúl E; Salomón, Claudio J; Lamas, María C

    2014-11-01

    Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30 min, while the microparticles prepared by external gelation released 67% within 30 min. It was observed that the AUC and Cmax values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.

  13. Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

    PubMed

    Küster, Tatiana; Stadelmann, Britta; Aeschbacher, Denise; Hemphill, Andrew

    2014-04-01

    The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

  14. Sustainability of soil-transmitted helminth control following a single-dose co-administration of albendazole and diethylcarbamazine.

    PubMed

    Rajendran, R; Mani, T R; Munirathinam, A; Sunish, I P; Abdullah, S Md; Augustin, D J; Satyanarayana, K

    2003-01-01

    We evaluated the long-term impact of single-dose diethylcarbamazine plus albendazole combination therapy with that of diethylcarbamazine alone on the control of soil-transmitted helminths (STH) in 2 blocks (revenue units) of Villupuram district, south India, as part of an ongoing mass drug administration (MDA) campaign for the elimination of lymphatic filariasis in 2001. The prevalence and intensities of STHs were studied in 287 children, aged 9 and 10 years (136 in the combination therapy cohort and 151 in the diethylcarbamazine alone cohort), using the Kato-Katz technique to examine stool samples at 4 time-points (baseline, and 3 weeks, 6 months and 11 months after MDA). The combination therapy showed long-term efficacy against STHs and the magnitude of control remained at a moderate and significant level for 11 months after MDA compared with the moderate gains of diethylcarbamazine alone. Single-dose MDA with albendazole and diethylcarbamazine combination therapy may prove to be a good strategy in treating multiple parasitic infections in endemic communities.

  15. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    NASA Astrophysics Data System (ADS)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  16. Distribution and organoleptic impact of sotolon enantiomers in dry white wines.

    PubMed

    Pons, Alexandre; Lavigne, Valérie; Landais, Yannick; Darriet, Philippe; Dubourdieu, Denis

    2008-03-12

    The enantiomers of sotolon, a flavor compound typical of oxidized white wines, were separated by preparative HPLC to determine their perception thresholds and distribution in wines. The enantiomeric ratios of chiral sotolon were evaluated in several dry white wines using gas chromatography and a chiral column (beta-cyclodextrin) connected to a 2 m precolumn (BP20). The perception threshold of (S)-sotolon (0.8 microg/L) in model wine solution was 100 times lower than that of the (R) form (89 microg/L), indicating that (S)-sotolon contributes to the characteristic aroma of prematurely aged dry white wines. Both enantiomers are detected in white wines. Analysis of commercial dry white wines from various vintages and origins revealed three types of distribution patterns: the racemic form, an excess of R, and an excess of S. The proportions found in these wines may be partially explained by the slow racemization kinetics (20 months) of optically active sotolon.

  17. Recent progress of chiral stationary phases for separation of enantiomers in gas chromatography.

    PubMed

    Xie, Sheng-Ming; Yuan, Li-Ming

    2017-01-01

    Chromatography techniques based on chiral stationary phases are widely used for the separation of enantiomers. In particular, gas chromatography has developed rapidly in recent years due to its merits such as fast analysis speed, lower consumption of stationary phases and analytes, higher column efficiency, making it a better choice for chiral separation in diverse industries. This article summarizes recent progress of novel chiral stationary phases based on cyclofructan derivatives and chiral porous materials including chiral metal-organic frameworks, chiral porous organic frameworks, chiral inorganic mesoporous materials, and chiral porous organic cages in gas chromatography, covering original research papers published since 2010. The chiral recognition properties and mechanisms of separation toward enantiomers are also introduced.

  18. (S)-Ibuprofen-imprinted polymers incorporating gamma-methacryloxypropyl-trimethoxysilane for CEC separation of ibuprofen enantiomers.

    PubMed

    Deng, Qi-Liang; Lun, Zhi-Hong; Gao, Ru-Yu; Zhang, Li-Hua; Zhang, Wei-Bing; Zhang, Yu-Kui

    2006-11-01

    In this report, a novel preparation method of molecularly imprinted polymers (MIPs) for CEC was developed. Molecularly imprinted monolithic columns for (S)-ibuprofen were prepared and evaluated, in which charged entities responsible for establishing EOF have been derived from gamma-methacryloxypropyltrimethoxysilane (gamma-MAPS), which was hydrolyzed following copolymerization with 4-vinylpyridine (4-VPY) and ethylene glycol dimethacrylate (EDMA). The EOF and molecular recognition of the stationary phase were investigated in aqueous and nonaqueous media, respectively. The experimental results indicated that the material showed a reasonably stable EOF and the prepared separation materials were capable of separating racemic ibuprofen, a task that could not be accomplished by MIPs prepared in parallel, using methacrylic acid (MAA) as a functional monomer. The efficiency at pH 3.2 for the first-eluted enantiomer and the last-eluted enantiomer (the imprinted analyte) were 128,700 and 2100 plates/m, respectively.

  19. Dosimetry of D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine

    SciTech Connect

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1985-01-01

    We have previously reported the radiation dosimetry of /sup 11/C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of /sup 11/C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs.

  20. Adsorption of ibuprofen enantiomers on a chiral stationary phase with a grafted antibiotic eremomycin

    NASA Astrophysics Data System (ADS)

    Reshetova, E. N.; Asnin, L. D.

    2015-02-01

    The adsorption of ibuprofen enantiomers on a chiral stationary phase Nautilus-E with a grafted antibiotic eremomycin from aqueous ethanol acetate buffer solutions was studied by chromatography. The ethanol concentration in the mobile phase was varied from 40 to 60 vol %. The adsorption isotherms of both enantiomers had a complex shape characterized by non-Langmuir type curvature and the presence of an inflection point. This is explained by two factors: the energy heterogeneity of the surface of the stationary phase and the dissociation of ibuprofen in the liquid phase. The effect of the system peak on the shape of the chromatograms of the target component was investigated. The temperature effect on the adsorption equilibrium was discussed.

  1. Three pairs of alkaloid enantiomers from the root of Isatis indigotica

    PubMed Central

    Liu, Yufeng; Wang, Xiaoliang; Chen, Minghua; Lin, Sheng; Li, Li; Shi, Jiangong

    2016-01-01

    Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(−)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(−)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(−)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(−)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products. PMID:27006898

  2. Experimental and Theoretical Evidence for Diastereomer- and Enantiomer-Specific Accumulation and Biotransformation of HBCD in Maize Roots.

    PubMed

    Huang, Honglin; Zhang, Shuzhen; Lv, Jitao; Wen, Bei; Wang, Sen; Wu, Tong

    2016-11-15

    Diastereomer- and enantiomer-specific accumulation and biotransformation of hexabromocyclododecane (HBCD) in maize (Zea mays L.) were investigated. Molecular interactions of HBCD with plant enzymes were further characterized by homology modeling combined with molecular docking. The (-)α-, (-)β-, and (+)γ-HBCD enantiomers accumulated to levels in maize significantly higher than those of their corresponding enantiomers. Bioisomerization from (+)/(-)-β- and γ-HBCDs to (-)α-HBCD was frequently observed, and (-)γ-HBCD was most easily converted, with bioisomerization efficiency of 90.5 ± 8.2%. Mono- and dihydroxyl HBCDs, debrominated metabolites including pentabromocyclododecene (PBCDe) and tetrabromocyclododecene (TBCDe), and HBCD-GSH adducts were detected in maize roots. Patterns of hydroxylated and debrominated metabolites were significantly different among HBCD diastereomers and enantiomers. Three pairs of HBCD enantiomers were selectively bound into the active sites and interacted with specific residues of maize enzymes CYP71C3v2 and GST31. (+)α-, (-)β-, and (-)γ-HBCDs preferentially bound to CYP71C3v2, whereas (-)α-, (-)β-, and (+)γ-HBCDs had strong affinities to GST31, consistent with experimental observations that (+)α-, (-)β-, and (-)γ-HBCDs were more easily hydroxylated, and (-)α-, (-)β-, and (+)γ-HBCDs were more easily isomerized and debrominated in maize compared to their corresponding enantiomers. This study for the first time provided both experimental and theoretical evidence for stereospecific behaviors of HBCD in plants.

  3. Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease

    PubMed Central

    Du, Fang; Bowman, Connor F.; Yan, Shirley S.

    2016-01-01

    Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice (APP+/MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP+ mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP+/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression. PMID:26786779

  4. A Method for the Quantitation of Trace Levels of Dimethyl Sulfoxide in Urine by High Performance Liquid Chromatography

    DTIC Science & Technology

    1989-05-01

    HIGH PERFORMANCE LIQUID CHROMATOGRAPHY by...for the sample cleanup and concentration, followed by separation by reversed phase high performance liquid chromatography . EXPERIMENTAL Materials...DIMETHYL SULFOXIDE IN URINE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY 4. AUTHORS (Last name, first name, middle initial. If military, show rank, e.g.

  5. Determination of Dimethyl Sulfoxide (DMSO), Ethanol (ETOH), Formamide (F) and Glycerol/Formal (GF) by High Performance Liquid Chromatography (HPLC)

    DTIC Science & Technology

    1989-01-30

    HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC...Classification) (U) Determination of Dimethyl Sulfoxide (DMSO), Ethanol, (ETOH), Formamide (F), and Glycerol/ Formal (GF) by High Performance Liquid Chromatography (HPLC...and 5). High performance liquid chromatography (HPLC) was the analytical method of choice for analyzing DMSO, ethanol, formamide and

  6. Purification and properties of Escherichia coli dimethyl sulfoxide reductase, an iron-sulfur molybdoenzyme with broad substrate specificity.

    PubMed

    Weiner, J H; MacIsaac, D P; Bishop, R E; Bilous, P T

    1988-04-01

    Dimethyl sulfoxide reductase, a terminal electron transfer enzyme, was purified from anaerobically grown Escherichia coli harboring a plasmid which codes for dimethyl sulfoxide reductase. The enzyme was purified to greater than 90% homogeneity from cell envelopes by a three-step purification procedure involving extraction with the detergent Triton X-100, chromatofocusing, and DEAE ion-exchange chromatography. The purified enzyme was composed of three subunits with molecular weights of 82,600, 23,600, and 22,700 as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native molecular weight was determined by gel electrophoresis to be 155,000. The purified enzyme contained 7.5 atoms of iron and 0.34 atom of molybdenum per mol of enzyme. The presence of molybdopterin cofactor in dimethyl sulfoxide reductase was identified by reconstitution of cofactor-deficient NADPH nitrate reductase activity from Neurospora crassa nit-I mutant and by UV absorption and fluorescence emission spectra. The enzyme displayed a very broad substrate specificity, reducing various N-oxide and sulfoxide compounds as well as chlorate and hydroxylamine.

  7. Rhodium-catalyzed imination of sulfoxides and sulfides: efficient preparation of N-unsubstituted sulfoximines and sulfilimines.

    PubMed

    Okamura, Hiroaki; Bolm, Carsten

    2004-04-15

    The Rh(II)-catalyzed imination of sulfoxides and sulfides using [Rh(2)(OAc)(4)] as a catalyst and trifluoroacetamide or sulfonylamides in combination with iodobenzene diacetate and magnesium oxide affords sulfoximines and sulfilimines, respectively, in a stereospecific manner. [reaction: see text

  8. Host-guest complexation of cucurbit[8]uril with two enantiomers

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Zheng; Lin, Rui-Lian; Bai, Dong; Tao, Zhu; Liu, Jing-Xin; Xiao, Xin

    2017-03-01

    Host-guest complexation of cucurbit[8]uril (Q[8]) with two enantiomers, D-3-(2-naphthyl)-alanine (D-NA) and L-3-(2-naphthyl)-alanine (L-NA), has been fully investigated. Experimental data indicate that double guests reside within the cavity of Q[8] in both aqueous solution and solid state, generating highly stable homoternary complexes D-NA2@Q[8] and L-NA2@Q[8].

  9. Hg(II) Coordination Studies in Penicillamine Enantiomers by 199mHg-TDPAC

    NASA Astrophysics Data System (ADS)

    Tröger, W.; ISOLDE Collaboration

    2001-11-01

    In order to study the binding of the toxic heavy metal ion Hg2+ to penicillamine, complexes with the D- and L-enantiomers of penicillamine were investigated by the nuclear quadrupole interaction of 199Hg monitored by time differential perturbed angular correlation spectroscopy. It was found that bound Hg(II) occurs in two-fold, three-fold and four-fold coordinations.

  10. Separation of VX, RVX and GB Enantiomers Using Liquid ChromatographyTime-of-Flight Mass Spectrometry

    DTIC Science & Technology

    2016-02-01

    Army Edgewood Chemical Biological Center (Aberdeen Proving Ground , MD). Samples were made at a 100 µg/mL level for analytical separation and a 22 mg/mL...AVAILABILITY STATEMENT Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT: Chemical nerve agents such...Phenomenex; Torrance, CA) was used to separate the enantiomers for all V and G agents within 15 min. Atmospheric pressure chemical ionization mode was

  11. Host-guest complexation of cucurbit[8]uril with two enantiomers

    PubMed Central

    Gao, Zhong-Zheng; Lin, Rui-Lian; Bai, Dong; Tao, Zhu; Liu, Jing-Xin; Xiao, Xin

    2017-01-01

    Host-guest complexation of cucurbit[8]uril (Q[8]) with two enantiomers, D-3-(2-naphthyl)-alanine (D-NA) and L-3-(2-naphthyl)-alanine (L-NA), has been fully investigated. Experimental data indicate that double guests reside within the cavity of Q[8] in both aqueous solution and solid state, generating highly stable homoternary complexes D-NA2@Q[8] and L-NA2@Q[8]. PMID:28300189

  12. Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats

    PubMed Central

    Gregg, Ryan A; Baumann, Michael H; Partilla, John S; Bonano, Julie S; Vouga, Alexandre; Tallarida, Christopher S; Velvadapu, Venkata; Smith, Garry R; Peet, M Melissa; Reitz, Allen B; Negus, S Stevens; Rawls, Scott M

    2015-01-01

    Background and Purpose Synthetic cathinones, commonly referred to as ‘bath salts’, are a group of amphetamine-like drugs gaining popularity worldwide. 4-Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate-type releaser at monoamine transporters. Similar to other cathinone-related compounds, MEPH has a chiral centre and exists stably as two enantiomers: R-mephedrone (R-MEPH) and S-mephedrone (S-MEPH). Experimental Approach Here, we provide the first investigation into the neurochemical and behavioural effects of R-MEPH and S-MEPH. We analysed both enantiomers in rat brain synaptosome neurotransmitter release assays and also investigated their effects on locomotor activity (e.g. ambulatory activity and repetitive movements), behavioural sensitization and reward. Key Results Both enantiomers displayed similar potency as substrates (i.e. releasers) at dopamine transporters, but R-MEPH was much less potent than S-MEPH as a substrate at 5-HT transporters. Locomotor activity was evaluated in acute and repeated administration paradigms, with R-MEPH producing greater repetitive movements than S-MEPH across multiple doses. After repeated drug exposure, only R-MEPH produced sensitization of repetitive movements. R-MEPH produced a conditioned place preference whereas S-MEPH did not. Lastly, R-MEPH and S-MEPH produced biphasic profiles in an assay of intracranial self-stimulation (ICSS), but R-MEPH produced greater ICSS facilitation than S-MEPH. Conclusions and Implications Our data are the first to demonstrate stereospecific effects of MEPH enantiomers and suggest that the predominant dopaminergic actions of R-MEPH (i.e. the lack of serotonergic actions) render this stereoisomer more stimulant-like when compared with S-MEPH. This hypothesis warrants further study. PMID:25255824

  13. Membrane interactivity of charged local anesthetic derivative and stereoselectivity in membrane interaction of local anesthetic enantiomers

    PubMed Central

    Tsuchiya, Hironori; Mizogami, Maki

    2008-01-01

    With respect to the membrane lipid theory as a molecular mechanism for local anesthetics, two critical subjects, the negligible effects of charged drugs when applied extracellularly and the stereoselective effects of enantiomers, were verified by paying particular attention to membrane components, phospholipids with the anionic property, and cholesterol with several chiral carbons. The membrane interactivities of structurally-different anesthetics were determined by their induced fluidity changes of liposomal membranes. Lidocaine (3.0 μmol/mL) fluidized phosphatidylcholine membranes, but not its quaternary derivative QX-314 (3.0 μmol/mL). Similarly to the mother molecule lidocaine, however, QX-314 fluidized phosphatidylserine-containing nerve cell model membranes and acidic phospholipids-constituting membranes depending on the acidity of membrane lipids. Positively charged local anesthetics are able to act on lipid bilayers by ion-pairing with anionic (acidic) phospholipids. Bupivacaine (0.75 mol/mL) and ropivacaine (0.75 and 1.0 μmol/mL) fluidized nerve cell model membranes with the potency being S(−)-enantiomer < racemate < R(+)-enantiomer (P < 0.01, vs antipode and racemate) and cardiac cell model membranes with the potency being S(−)-ropivacaine < S(−)-bupivacaine < R(+)-bupivacaine (P < 0.01). However, their membrane effects were not different when removing cholesterol from the model membranes. Stereoselectivity is producible by cholesterol which increases the chirality of lipid bilayers and enables to discriminate anesthetic enantiomers. The membrane lipid interaction should be reevaluated as the mode of action of local anesthetics. PMID:22915858

  14. Membrane interactivity of charged local anesthetic derivative and stereoselectivity in membrane interaction of local anesthetic enantiomers.

    PubMed

    Tsuchiya, Hironori; Mizogami, Maki

    2008-01-01

    With respect to the membrane lipid theory as a molecular mechanism for local anesthetics, two critical subjects, the negligible effects of charged drugs when applied extracellularly and the stereoselective effects of enantiomers, were verified by paying particular attention to membrane components, phospholipids with the anionic property, and cholesterol with several chiral carbons. The membrane interactivities of structurally-different anesthetics were determined by their induced fluidity changes of liposomal membranes. Lidocaine (3.0 μmol/mL) fluidized phosphatidylcholine membranes, but not its quaternary derivative QX-314 (3.0 μmol/mL). Similarly to the mother molecule lidocaine, however, QX-314 fluidized phosphatidylserine-containing nerve cell model membranes and acidic phospholipids-constituting membranes depending on the acidity of membrane lipids. Positively charged local anesthetics are able to act on lipid bilayers by ion-pairing with anionic (acidic) phospholipids. Bupivacaine (0.75 mol/mL) and ropivacaine (0.75 and 1.0 μmol/mL) fluidized nerve cell model membranes with the potency being S(-)-enantiomer < racemate < R(+)-enantiomer (P < 0.01, vs antipode and racemate) and cardiac cell model membranes with the potency being S(-)-ropivacaine < S(-)-bupivacaine < R(+)-bupivacaine (P < 0.01). However, their membrane effects were not different when removing cholesterol from the model membranes. Stereoselectivity is producible by cholesterol which increases the chirality of lipid bilayers and enables to discriminate anesthetic enantiomers. The membrane lipid interaction should be reevaluated as the mode of action of local anesthetics.

  15. Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine

    PubMed Central

    Polcaro, Chiara M.; Donati, Enrica; Cao, Xiaohang; Basso, Annalisa; Guidi, Alessandra; Rugel, Anastasia R.; Holloway, Stephen P.; Anderson, Timothy J. C.; Hart, P. John; Cioli, Donato; LoVerde, Philip T.

    2015-01-01

    Background For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Methodology/Principal Findings Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Conclusions/Significance Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. PMID:26485649

  16. Determination of Carvedilol Enantiomers in Pharmaceutical Dosages by SBSE-HPLC Based on Diastereomer Formation.

    PubMed

    Taraji, Maryam; Talebpour, Zahra; Adib, Nuoshin; Karimi, Shima; Haghighi, Farideh; Aboul-Enein, Hassan Y

    2015-09-01

    A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 µg L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method.

  17. Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano-Sorbent Modified by a Chiral Selector.

    PubMed

    Tarhan, Tuba; Tural, Bilsen; Tural, Servet; Topal, Giray

    2015-11-01

    In this study, R(+)-α-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo-second-order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g(-1). The magnetic chiral sorbent has a greater affinity for (S)-(+)-mandelic acid compared to (R)-(-)-mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD-H column.

  18. Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.

    PubMed

    Bakhtiar, Ray; Tse, Francis L S

    2004-06-01

    Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented.

  19. Selective nuclei accumulation of ruthenium(II) complex enantiomers that target G-quadruplex DNA.

    PubMed

    Sun, Dongdong; Liu, Yanan; Yu, Qianqian; Liu, Du; Zhou, Yanhui; Liu, Jie

    2015-09-01

    Different enantiomers exhibit large differences in their biological activity and/or toxicity, but they rarely involve the relationship of the agents for molecular and cellular imaging with the chiral structure of ruthenium complexes. Here, we report that an enantiomer of a polypyridyl ruthenium complex can selectively accumulate in the nucleus of HepG2 cells. Confocal laser scanning microscopy studies show that this phenomenon occurs via a non-endocytotic, but temperature-dependent, mechanism of cellular uptake in HepG2 cells. DNA oligonucleotides with repetitive tracts of guanine bases that can form G-quadruplex structures have aroused interest as therapeutic agents and as targets for anticancer drug design. Various biophysical techniques show that the Λ-enantiomer of ruthenium complexes can selectively stabilize human telomeric G-quadruplex DNA and has a strong preference for G-quadruplex over duplex DNA. Judged from the NMR results, we speculate that at higher 4:1 ligand/G-quadruplex stoichiometry, complex Λ-Ru is likely to bind with each groove of the tetraplex in a dimeric form or intercalate with the G-tetrad in the 3' terminal face and coexist with other modes. The molecular modeling analysis is in agreement with the NMR titrations performed in this investigation indicating that ruthenium complexes are actually characterized by a mixed binding mode. The results provide many opportunities for the development of novel agents for living cell-related studies.

  20. Enantiomer-specific in vitro biotransformation of select pharmaceuticals in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Connors, Kristin A; Du, Bowen; Fitzsimmons, Patrick N; Chambliss, C Kevin; Nichols, John W; Brooks, Bryan W

    2013-11-01

    The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well-studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CL(IN VITRO,INT)). No biotransformation was observed for rac-, R-, or S-fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans, S(-)-propranolol was more rapidly cleared than the R(+)-enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed.

  1. Structural and functional characterization of the enantiomers of the antischistosomal drug oxamniquine

    DOE PAGES

    Taylor, Alexander B.; Pica-Mattoccia, Livia; Polcaro, Chiara M.; ...

    2015-10-20

    For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, whilemore » R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. In conclusion, these findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds.« less

  2. Structural and functional characterization of the enantiomers of the antischistosomal drug oxamniquine

    SciTech Connect

    Taylor, Alexander B.; Pica-Mattoccia, Livia; Polcaro, Chiara M.; Donati, Enrica; Cao, Xiaohang; Basso, Annalisa; Guidi, Alessandra; Rugel, Anastasia R.; Holloway, Stephen P.; Anderson, Timothy J.C.; Hart, P. John; Cioli, Donato; LoVerde, Philip T.

    2015-10-20

    For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. In conclusion, these findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds.

  3. Sequential micellar electrokinetic chromatography analysis of racemization reaction of alanine enantiomers.

    PubMed

    Fu, Rao; Liu, Lina; Guo, Yingna; Guo, Liping; Yang, Li

    2014-02-28

    A novel method for online monitoring racemization reaction of alanine (Ala) enantiomers was developed, by combining sequential sample injection and micellar electrokinetic chromatography (MEKC) technique. Various conditions were investigated to optimize the sequential injection, Ala derivatization and MEKC chiral separation of d-/l-Ala. High reproducibility of the sequential MEKC analysis was demonstrated by analyzing the standard Ala samples, with relative standard deviation values (n=20) of 1.35%, 1.98%, and 1.09% for peak height, peak area and migration time, respectively. Ala racemization was automatically monitored every 40s from the beginning to the end of the reaction, by simultaneous detection of the consumption of the substrate enantiomer and the formation of the product enantiomer. The Michaelis constants of the racemization reaction were obtained by the sequential MEKC method, and were in good agreement with those obtained by traditional off-line enzyme assay. Our study indicated that the present sequential MEKC method can perform fast, efficient, accurate and reproducible analysis of racemization reaction of amino acids, which is of great importance for the determination of the activity of racemase and thus understanding its metabolic functions.

  4. [Determination of 13C enrichment in soil amino acid enantiomers by gas chromatogram/mass spectrometry].

    PubMed

    He, Hong-Bo; Zhang, Wei; Ding, Xue-Li; Bai, Zhen; Liu, Ning; Zhang, Xu-Dong

    2008-06-01

    The transformation and renewal of amino acid enantiomers is of significance in indicating the turnover mechanism of soil organic matter. In this paper, a method of gas chromatogram/mass spectrometry combined with U-13 C-glucose incubation was developed to determine the 13C enrichment in soil amino acid enantiomers, which could effectively differentiate the original and the newly synthesized amino acids in soil matrix. The added U-13 C-glucose was utilized rapidly to structure the amino acid carbon skeleton, and the change of relative abundance of isotope ions could be determined by mass spectrometry. The direct incorporation of U-13 C glucose was estimated by the intensity increase of m/z (F + n) to F (F was parent fragment, and n was the carbon number in the fragment), while the total isotope incorporation from the added 13C could be calculated according to the abundance ratio increment summation from m/z (Fa + 1) through (Fa + T) (Fa was the fragment containing all original skeleton carbons, and T was the carbon number in the amino acid molecule). The 13C enrichment in the target compound was expressed as atom percentage excess (APE), and that of D-amino acid needed to be corrected by the coefficient of hydrolysis-induced racemization. The 13C enrichment reflected the carbon turnover velocity of individual amino acid enantiomers, and was powerful to investigate the dynamics of soil amino acids.

  5. Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity.

    PubMed

    Voith, K; Cummings, J R

    1976-08-01

    Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms.

  6. Effectiveness of Albendazole for Hookworm Varies Widely by Community and Correlates with Nutritional Factors: A Cross-Sectional Study of School-Age Children in Ghana.

    PubMed

    Humphries, Debbie; Nguyen, Sara; Kumar, Sunny; Quagraine, Josephine E; Otchere, Joseph; Harrison, Lisa M; Wilson, Michael; Cappello, Michael

    2017-02-08

    Mass drug administration (MDA) targeting school-age children is recommended by the World Health Organization for the global control of soil-transmitted helminth (STH) infections. Although considered safe and cost-effective to deliver, benzimidazole anthelminthics are variably effective against the three most common STHs, and widespread use has raised concern about the potential for emerging resistance. To identify factors mediating response to albendazole, we conducted a cross-sectional study of hookworm infection in the Kintampo North Municipality of Ghana in 2011. Among 140 school-age children residing in five contiguous communities, the hookworm prevalence was 59% (82/140). The overall cure rate following administration of single-dose albendazole (400 mg) was 35% (27/76), with a community-wide fecal egg reduction rate (ERR) of 61% (95% confidence interval: 51.8-71.1). Significant disparities were observed in albendazole effectiveness by community, with a cure rate as low as 0% (N = 24) in Jato Akuraa and ERRs ranging from 53% to 95% across the five study sites. Individual host factors associated with response to deworming treatment included time since last meal, pretreatment blood hemoglobin level, and mid-upper arm circumference. These data demonstrate significant community-level variation in the effectiveness of albendazole, even among populations living in close proximity. Identification of host factors that influence response to albendazole, most notably the timing of drug administration and nutritional factors, creates an opportunity to enhance the effectiveness of deworming through targeted interventions. These findings also demonstrate the importance of measuring anthelminthic response as part of the monitoring and evaluation of community-based deworming programs.

  7. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    PubMed

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  8. Onychomycosis treated with a dilute povidone–iodine/dimethyl sulfoxide preparation

    PubMed Central

    Capriotti, Kara; Capriotti, Joseph A

    2015-01-01

    Background Povidone–iodine (PVP-I) 10% aqueous solution is a well-known, nontoxic, commonly used topical antiseptic with no reported incidence of fungal resistance. We have been using a low-dose formulation of 1% PVP-I (w/w) in a solution containing dimethyl sulfoxide (DMSO) in our clinical practice for a variety of indications. Presented here is our clinical experience with this novel formulation in a severe case of onychomycosis that was resistant to any other treatment. Findings A 49-year-old woman who had been suffering from severe onychomycosis for years presented after failing to find any remedy including over the counter (OTC), topical, and systemic oral prescribed therapies. Conclusion The topical povidone–iodine/DMSO system was very effective in this case at alleviating the signs and symptoms of onychomycosis. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility. PMID:26491374

  9. Electrical conductivity of solutions of copper(II) nitrate crystalohydrate in dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Mamyrbekova, Aigul K.; Mamitova, A. D.; Mamyrbekova, Aizhan K.

    2016-06-01

    Conductometry is used to investigate the electric conductivity of Cu(NO3)2 ṡ 3H2O solutions in dimethyl sulfoxide in the 0.01-2.82 M range of concentrations and at temperatures of 288-318 K. The limiting molar conductivity of the electrolyte and the mobility of Cu2+ and NO 3 - ions, the effective coefficients of diffusion of copper(II) ions and nitrate ions, and the degree and constant of electrolytic dissociation are calculated for different temperatures from the experimental results. It is established that solutions containing 0.1-0.6 M copper nitrate trihydrate in DMSO having low viscosity and high electrical conductivity can be used in electrochemical deposition.

  10. Strong intermolecular exciton couplings in solid-state circular dichroism of aryl benzyl sulfoxides.

    PubMed

    Padula, Daniele; Di Pietro, Sebastiano; Capozzi, Maria Annunziata M; Cardellicchio, Cosimo; Pescitelli, Gennaro

    2014-09-01

    A series of 13 enantiopure aryl benzyl sulfoxides () with different substituents on the two aromatic rings has been previously analyzed by means of electronic circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and their X-ray structure is established. For almost one-half of the series, CD spectra measured in the solid state were quite different from those in acetonitrile solution. We demonstrate that the difference is due to strong exciton couplings between molecules packed closely together in the crystal. The computational approach consists of time-dependent density functional theory (TDDFT) calculations run on "dimers" composed of nearest neighbors found in the lattice. Solid-state CD spectra are well reproduced by the average of all possible pairwise terms. The relation between the crystal space group and conformation, and the appearance of solid-state CD spectra, is also discussed.

  11. Inactivation kinetics of polyphenol oxidase from pupae of blowfly (Sarcophaga bullata) in the dimethyl sulfoxide solution.

    PubMed

    Chen, Chao-Qi; Li, Zhi-Cong; Pan, Zhi-Zhen; Zhu, Yu-Jing; Yan, Ruo-Rong; Wang, Qin; Yan, Jiang-Hua; Chen, Qing-Xi

    2010-04-01

    The effects of dimethyl sulfoxide (DMSO) on the activity of polyphenol oxidase (PPO, EC 1.14.18.1) from blowfly pupae for the oxidation of L-3,4-dihydroxyphenylalanine were studied. The results showed that low concentrations of DMSO could lead to reversible inactivation to the enzyme. The IC(50) value, the inactivator concentration leading to 50% activity lost, was estimated to be 2.35 M. Inactivation of the enzyme by DMSO was classified as mixed type. The kinetics of inactivation of PPO from blowfly pupae in the low concentrations of DMSO solution was studied using the kinetic method of the substrate reaction. The rate constants of inactivation were determined. The results show that k(+0) was much larger than k'(+0), indicating that the free enzyme molecule was more fragile than the enzyme-substrate complex in the DMSO solution. It was suggested that the presence of the substrate offers marked protection of this enzyme against inactivation by DMSO.

  12. Changing electrical properties of PEDOT:PSS by incorporating with dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Lin, Yow-Jon; Lee, Jhe-You; Chen, Shang-Min

    2016-11-01

    The effect of incorporation of dimethyl sulfoxide (DMSO) into poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) on the electrical conductivity is investigated. It is shown that the values of the carrier mobility and the carrier density increase significantly for PEDOT:PSS films with DMSO addition. The high carrier mobility of PEDOT:PSS samples with the addition of DMSO is attributed to a combined effect of the modification of the electron-phonon coupling and a change in the value of the PSS-to-PEDOT ratio. The high carrier density of PEDOT:PSS samples with DMSO addition is attributed to a high affinity of DMSO for water.

  13. In situ observation of electrolyte-concentration-dependent solid electrolyte interphase on graphite in dimethyl sulfoxide.

    PubMed

    Liu, Xing-Rui; Wang, Lin; Wan, Li-Jun; Wang, Dong

    2015-05-13

    High lithium salt concentration strategy has been recently reported to be an effective method to enable various organic solvents as electrolyte of Li-ion batteries. Here, we utilize in situ atomic force microscopy (AFM) to investigate the interfacial morphology on the graphite electrode in dimethyl sulfoxide (DMSO)-based electrolyte of various concentrations. The significant differences in interfacial features of the graphite in electrolytes of different concentrations are revealed. In the concentrated electrolyte, stable films form primarily at the step edges and defects on the graphite surface after initial electrochemical cycling. On the other hand, in the dilute electrolyte, DMSO-solvated lithium ions constantly intercalate into graphite layers, and serious decomposition of solvent accompanied by structural deterioration of the graphite surface is observed. The in situ AFM results provide direct evidence for the concentration-dependent interface reactions between graphite electrode and DMSO-based electrolyte.

  14. [Effective dimethyl sulfoxide (DMSO) occlusive dressing technique for amyloidosis of the urinary bladder].

    PubMed

    Hasegawa, Yoshihiro; Kanda, Hideki; Miki, Manabu; Masui, Satoru; Yoshio, Yuko; Yamada, Yasushi; Soga, Norihito; Arima, Kiminobu; Sugimura, Yoshiki

    2013-10-01

    A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.

  15. An approach for prominent enhancement of the quality of konjac flour: dimethyl sulfoxide as medium.

    PubMed

    Ye, Ting; Wang, Ling; Xu, Wei; Liu, Jinjin; Wang, Yuntao; Zhu, Kunkun; Wang, Sujuan; Li, Bin; Wang, Chao

    2014-01-01

    In this paper, an approach to improve several konjac flour (KF) qualities by dimethyl sulfoxide (DMSO) addition using various concentrations at different temperature levels was proposed. Also, various properties of native and refined KF, including transparency, chemical composition and rheological properties have been investigated. The results showed that the KF refined by 75% DMSO achieved 27.7% improvement in transparency, 99.7% removal of starch, 99.4% removal of soluble sugar, and 98.2% removal of protein as well as more satisfactory viscosity stability. In addition, the morphology structure of refined KF showed a significant difference compared with the native one as observed using the SEM, which is promising for further industrial application. Furthermore, the rheological properties of both native and refined konjac sols were studied and the results showed that DMSO refinement is an effective and alternative approach to improve the qualities of KF in many aspects.

  16. Carnitine or dimethyl sulfoxide, or both, for the treatment of anthracycline extravasation in rats.

    PubMed

    Uzunoglu, Sernaz; Cosar, Rusen; Cicin, Irfan; Ibis, Kamuran; Demiralay, Ebru; Benlier, Erol; Erdogan, Bulent; Kandulu, Huseyin; Ozen, Alaattin; Altaner, Semsi

    2013-10-01

    This study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200-225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.

  17. Thermal characterization of ZnO-DMSO (dimethyl sulfoxide) colloidal dispersions using the inverse photopyroelectric technique.

    PubMed

    Marín, E; Calderón, A; Díaz, D

    2009-05-01

    Nanofluids, i.e., colloidal dispersions of nanoparticles in a base liquid (solvent), have received considerable attention in the last years due to their potential applications. One attractive feature of these systems is that their thermal conductivity can exceed the corresponding values of the base fluid and of the fluid with large particles of the same chemical composition. However, there is a lack of agreement between published results and the suggested mechanisms which explain the thermal conductivity enhancement. Here we show the possibilities of the inverse photopyroelectric method for the determination of the effective thermal effusivity of the system constituted by small ZnO nanoparticles dispersed in dimethyl sulfoxide, as a function of the nanoparticles volumetric fraction. Using a phenomenological model we estimated the thermal conductivity of these colloidal samples without observing any significant enhancement of this parameter above effective medium predictions.

  18. Membrane permeability of the human granulocyte to water, dimethyl sulfoxide, glycerol, propylene glycol and ethylene glycol.

    PubMed

    Vian, Alex M; Higgins, Adam Z

    2014-02-01

    Granulocytes are currently transfused as soon as possible after collection because they rapidly deteriorate after being removed from the body. This short shelf life complicates the logistics of granulocyte collection, banking, and safety testing. Cryopreservation has the potential to significantly increase shelf life; however, cryopreservation of granulocytes has proven to be difficult. In this study, we investigate the membrane permeability properties of human granulocytes, with the ultimate goal of using membrane transport modeling to facilitate development of improved cryopreservation methods. We first measured the equilibrium volume of human granulocytes in a range of hypo- and hypertonic solutions and fit the resulting data using a Boyle-van't Hoff model. This yielded an isotonic cell volume of 378 μm(3) and an osmotically inactive volume of 165 μm(3). To determine the permeability of the granulocyte membrane to water and cryoprotectant (CPA), cells were injected into well-mixed CPA solution while collecting volume measurements using a Coulter Counter. These experiments were performed at temperatures ranging from 4 to 37°C for exposure to dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol. The best-fit water permeability was similar in the presence of all of the CPAs, with an average value at 21°C of 0.18 μmatm(-1)min(-1). The activation energy for water transport ranged from 41 to 61 kJ/mol. The CPA permeability at 21°C was 6.4, 1.0, 8.4, and 4.0 μm/min for dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol, respectively, and the activation energy for CPA transport ranged between 59 and 68 kJ/mol.

  19. Dimeric molecular association of dimethyl sulfoxide in solutions of nonpolar liquids.

    PubMed

    Shikata, Toshiyuki; Sugimoto, Natsuki

    2012-01-26

    Although many vibrational spectroscopic studies using infrared (IR) absorption and Raman scattering (RS) techniques revealed that dimethyl sulfoxide (DMSO) forms intermolecular dimeric associations in the pure liquid state and in solutions, the results of a number of dielectric relaxation studies did not clearly show the presence of such dimers. Recently, we found the presence of dimeric DMSO associations in not only the pure liquid but also in solutions of nonpolar solvents, such as tetrachloromethane (CCl(4)) and benzene (Bz), using dielectric relaxation (DR) techniques, which ranged from 50 MHz to 50 GHz at 25 °C. The dimeric DMSO associations cause a slow dielectric relaxation process with a relaxation time of ca. 23 ps for solutions in CCl(4) (ca. 17 ps in Bz) due to the dissociation into monomeric DMSO molecules, while the other fast relaxation is caused by monomeric DMSO molecules with a relaxation time of ca. 5.0 ps (ca. 5.5 ps in Bz) at 25 °C. A comparison of DR and vibrational spectroscopic data for DMSO solutions demonstrated that the concentration dependence of the relative magnitude of the slow and fast DR strength corresponds well to the two IR and RS bands assigned to the vibrational stretching modes of the sulfoxide groups (S═O) of the dimeric associations and the monomeric DMSO molecules, respectively. Moreover, the concentrations of the dimeric associations ([DIM]) and monomeric DMSO molecules ([MON]) were governed by a chemical equilibrium and an equilibrium constant (K(d) = [DIM](2)[MON](-1)) that was markedly dependent on the concentration of DMSO and the solvent species (K(d) = 2.5 ± 0.5 M(-1) and 0.7 ± 0.1 M(-1) in dilute CCl(4) and Bz solutions, respectively, and dramatically increased to 20-40 M(-1) in pure DMSO at 25 °C).

  20. Use of pseudoracemic nitrendipine to elucidate the metabolic steps responsible for stereoselective disposition of nitrendipine enantiomers.

    PubMed Central

    Mast, V; Fischer, C; Mikus, G; Eichelbaum, M

    1992-01-01

    1. The pharmacokinetics, protein binding, bioavailability and metabolism of (+)-R- and (-)-S-nitrendipine were studied in six healthy subjects following random oral administration of 20 mg (+)-R-, 20 mg (-)-S- and 20 mg R,S-nitrendipine (pseudoracemic mixture of 10 mg [13C4)-(+)-R- and 10 mg (-)-S-enantiomer). 2. After administration of the enantiomers pronounced differences in AUC (R: 29.9 +/- 20.1; S: 123.8 +/- 63.7 ng ml-1 h; P less than 0.05), bioavailability (R: 10.7 +/- 7.4%; S: 44.6 +/- 23.1%; P less than 0.05) and Cmax (R: 14.4 +/- 7.7; S: 72.5 +/- 40.5 ng ml-1; P less than 0.05) were observed between R- and S-nitrendipine. When racemic nitrendipine was given bioavailability and dose normalized AUC and Cmax values of the S-enantiomer were not different from the values after S-nitrendipine-administration. In contrast, bioavailability (R: 10.7% R,S: 22.1%) and dose normalized AUC (R: 15.0; R,S: 29.5 ng ml-1 h and Cmax (R: 7.2; R,S: 16.8 ng ml-1) of R-nitrendipine were doubled following R,S- as compared with R-nitrendipine administration. t1/2 (R: 9.8; S: 9.1 h) and tmax were not different between the enantiomers nor were the values different after administration of the enantiomers or racemate. The fraction unbound in serum of R-nitrendipine was 0.0098 +/- 0.0032 (s.d.) and that of S-nitrendipine was 0.0083 +/- 0.0015 (s.d.). 3. The AUC values of the major pyridine metabolite M1 were similar after administration of R- and S-nitrendipine (S: 114.7 +/- 48.5; R: 71.7 +/- 29.9 ng ml-1 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1540491

  1. [Study on the effect of extraction behaviour of molybdenum (V) thiocyanate complex in the dimethyl sulfoxide and water system by spectrophotometry].

    PubMed

    Liang, Yu-zhen; Gao, Lian-bin; Qu, Zeng-lu; He, Zhong-lin

    2003-02-01

    In this paper the effect of petroleum sulfoxide-carbon tetrachloride used as extractant on the extraction behaviour of molybdenum (V) thiocyanate complex at different concentration of dimethyl sulfoxide and water system is studied by spectrophotometry. The mixture ratio of extraction is directly calculated using spectrophotometric data. Functional relation of mixture ratio and concentration of thiocyanate in mixed solution is discussed. By increasing the percent of volume of dimethyl sulfoxide in mixed solution, the effects of mixture ratio and percentage of extraction were studied. The experimental results were explained. It shows that the extraction system of MoO (SCN)3 has an application value.

  2. Enantioseparation and determination of triticonazole enantiomers in fruits, vegetables, and soil using efficient extraction and clean-up methods.

    PubMed

    Zhang, Qing; Gao, Beibei; Tian, Mingming; Shi, Haiyan; Hua, Xiude; Wang, Minghua

    2016-01-15

    An efficient and novel enantioseparation and determination method was developed to quantify the enantiomers of chiral triazole fungicide triticonazole in fruit, vegetable, and soil samples. Under the optimal chromatographic conditions, the enantiomers of triticonazole were completely enantioseparated on a cellulose tris(3-chloro-4-methyl phenyl carbamate) column with relatively good resolution (Rs=14.04). Two cleanup methods were compared to quantify the enantiomers of triticonazole. The modified QuEChERS (quick, easy, cheap, effective, rugged and safe) extraction procedure was achieved with sufficient recoveries and low detection limits. Good recoveries were obtained for the two enantiomers ranging from 84.1% to 103.2% in the six matrices, and the relative standard deviation values ranged from 1.7% to 8.4%. Under the optimal conditions, the obtained limits of detection (LODs) were in the range of 0.0012-0.0031mg/kg for the two enantiomers, and the limits of quantification (LOQs) were in the range of 0.0036-0.0091mg/kg, which were lower than the maximum residue levels established in Japan. In addition, the stereochemical structure of triticonazole enantiomers were determined for the first time using a combination of experimental and predicted electronic circular dichroism (ECD) spectra. The first eluted enantiomer was confirmed to be (+)-(S)-triticonazole. These results indicate that the proposed method is convenient and reliable for the enantioselective detection of triticonazole in authentic samples. The proposed method could be widely applicable for investigating the stereoselective degradation of triticonazole in food and environmental matrices, providing additional information for reliable risk assessment of triazole fungicides.

  3. [Effect of bolus administration of albendazole into the rumen on gastrointestinal nematodes and the Dicrocoelium dendriticum trematode in sheep].

    PubMed

    Corba, J; Krupicer, I; Várady, M; Pet'ko, B

    1994-01-01

    The efficacy of intraruminal albendazole (ABZ) capsules (Proftril-Captec) and the effect of treatment on productivity parameters were studied in two experiments totally on 466 ewes naturally infected with gastrointestinal nematodes and trematodes D. dendriticum. Ovoscopical tests revealed that treated animals remained negative during 10-12 weeks after the administration of capsules and that pasture contamination with helminths was significantly reduced. Necropsy revealed 96.9-99.2% efficacy against nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis. Priority finding is the efficacy of ABZ capsules against trematodes D. dendriticum which was in the first experiment 88.5% and in the second experiment 91.8%. During the 6-month pasture season treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls.

  4. Trichuris suis and Oesophagostomum dentatum Show Different Sensitivity and Accumulation of Fenbendazole, Albendazole and Levamisole In Vitro

    PubMed Central

    Hansen, Tina V. A.; Nejsum, Peter; Friis, Christian; Olsen, Annette; Thamsborg, Stig Milan

    2014-01-01

    Background The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known. Methodology We studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species. Principal findings The motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6–17.2%) as compared to O. dentatum (0.8–0.9%). Conclusion/Significance The general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum. PMID:24699263

  5. Spectral, thermal, kinetic, molecular modeling and eukaryotic DNA degradation studies for a new series of albendazole (HABZ) complexes

    NASA Astrophysics Data System (ADS)

    El-Metwaly, Nashwa M.; Refat, Moamen S.

    2011-01-01

    This work represents the elaborated investigation for the ligational behavior of the albendazole ligand through its coordination with, Cu(II), Mn(II), Ni(II), Co(II) and Cr(III) ions. Elemental analysis, molar conductance, magnetic moment, spectral studies (IR, UV-Vis and ESR) and thermogravimetric analysis (TG and DTG) have been used to characterize the isolated complexes. A deliberate comparison for the IR spectra reveals that the ligand coordinated with all mentioned metal ions by the same manner as a neutral bidentate through carbonyl of ester moiety and NH groups. The proposed chelation form for such complexes is expected through out the preparation conditions in a relatively acidic medium. The powder XRD study reflects the amorphous nature for the investigated complexes except Mn(II). The conductivity measurements reflect the non-electrolytic feature for all complexes. In comparing with the constants for the magnetic measurements as well as the electronic spectral data, the octahedral structure was proposed strongly for Cr(III) and Ni(II), the tetrahedral for Co(II) and Mn(II) complexes but the square-pyramidal for the Cu(II) one. The thermogravimetric analysis confirms the presence or absence of water molecules by any type of attachments. Also, the kinetic parameters are estimated from DTG and TG curves. ESR spectrum data for Cu(II) solid complex confirms the square-pyramidal state is the most fitted one for the coordinated structure. The albendazole ligand and its complexes are biologically investigated against two bacteria as well as their effective effect on degradation of calf thymus DNA.

  6. Enantiomer Profiling of Methamphetamine in White Crystal and Tablet Forms (Ma Old) Using LC-MS-MS.

    PubMed

    Wang, Ting; Yu, Zhiguo; Shi, Yan; Xiang, Ping

    2015-09-01

    At the global level, seizures of crystalline methamphetamine (MA) and MA tablets have risen to a new high, indicating that the substance is an imminent threat. MA enantiomer profiling was a useful tool to investigate the prevalence of MA abuse, the intrinsic characteristics of the seized samples and the trends of precursors. In this work, the distribution of enantiomers in clandestine MA crystals and tablets seized mainly in the Yangtze River Delta region, China, from 2008 to 2014 were identified. The MA samples were diluted with internal standard methanol solution, and analyzed by LC-MS-MS. The detection limits of the enantiomers were 0.04 μg/L. The limit of quantification was 0.1 μg/L. As little as 0.2% of the R-enantiomer ratio could be determined. Standard calibration curves of S- and R-MA showed good linearity in the range of 0.1-80 μg/L (r(2) > 0.995). All of the seizures were optically pure S-enantiomer in the years 2008 and 2009. Seized samples containing a slight amount of R-MA began to appear in 2010 and increased in the year 2014. No racemic mixture or R-isomer of MA was seized. From this study, we could find out that smuggling routes and/or precursors might be silently changing in the Yangtze River Delta region, China.

  7. Dimethyl sulfoxide participant iron-mediated cascade oxidation/α-formylation reaction of substituted 2,3-dihydropyrroles under air and protonic acid free condition.

    PubMed

    Zhang, Zhiguo; Tian, Qing; Qian, Jingjing; Liu, Qingfeng; Liu, Tongxin; Shi, Lei; Zhang, Guisheng

    2014-09-05

    An efficient and Brønsted acid free one-pot protocol to directly generate structurally sophisticated α-formylpyrrole derivatives in moderate to good yields has been demonstrated, involving an iron-mediated domino oxidation/formylation reaction of readily available 2,3-dihydro-1H-pyrroles in dimethyl sulfoxide and air atmosphere, in which dimethyl sulfoxide acts as the formyl donor. A possible mechanism is presented.

  8. Mulberry (Morus L.) methionine sulfoxide rreductase gene cloning, sequence analysis, and expression in plant development and stress response.

    PubMed

    Tong, Wei; Zhang, Yinghua; Wang, Heng; Li, Feng; Liu, Zhaoyue; Wang, Yuhua; Fang, Rongjun; Zhao, Weiguo; Li, Long

    2013-01-01

    Methionine sulfoxide reductase plays a regulatory role in plant growth and development, especially in scavenging reactive oxygen species by restoration of the oxidation of methionine in protein. A full-length cDNA sequence encoding methionine sulfoxide reductase (MSR) from mulberry, which we designated MMSR, was cloned based on mulberry expressed sequence tags (ESTs). Sequence analysis showed that the MMSR is 810 bp long, encoding 194 amino acids with a predicted molecular weight of 21.6 kDa and an isoelectric point of 6.78. The expression level of the MMSR gene under conditions of drought and salt stresses was quantified by qRT-PCR. The results show that the expression level changed significantly under the stress conditions compared to the normal growth environment. It helps us to get a better understanding of the molecular basis for signal transduction mechanisms underlying the stress response in mulberry.

  9. Cyclic sulfoxides garlicnins B2, B3, B4, C2, and C3 from Allium sativum.

    PubMed

    Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kohtaro; Ono, Masateru; Nakano, Daisuke; Kinjo, Junei

    2013-01-01

    Several novel sulfides, called garlicnins B2 (1), B3 (2), B4 (3), C2 (4), and C3 (5), were isolated from acetone extracts of garlic, Allium sativum L. and characterized. These garlicnins are capable of suppressing M2 macrophage activation and they have a novel skeleton of cyclic sulfoxide. The structures of the former 3 and latter of 2 were deduced to be 2-(sulfenic acid)-5-(allyl)-3,4-dimethyltetrahydrothiophene-S-oxides and 2-(allyldithiine)-5-(propenylsulfoxide)-3,4-dimethyltetrahydrothiophene-S-oxides, respectively. The mechanism of the proposed production of these compounds is discussed. The identification of these novel sulfoxides from garlic accumulates a great deal of new chemistry in the Allium sulfide field, and future pharmacological investigations of these compounds will aid the development of natural, healthy foods and anti-cancer agents that may prevent or combat disease.

  10. Single enantiomer versus racemate: chiral distinction in the proton pump inhibitors omeprazole and esomeprazole.

    PubMed

    Marom, Hili; Pogodin, Sergey; Agranat, Israel

    2014-04-01

    Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral-switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6-311G(d,p), the 6-methoxy∙∙∙6-methoxy and 5-methoxy∙∙∙5-methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG(298,(RS-SS))) between the cyclic C2-(S,S)- and Ci-(R,S)-dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and -6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of -3.3 kJ/mol, indicating a reversal of the order of the relative stabilities of C2-(S,S)- and Ci-(R,S)-dimers. The chiral distinction free energies between the corresponding (less stable) C1-dimers with one intermolecular hydrogen bond are -9.3, -5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and -3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer-enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole-related combination drug Vimovo.

  11. Isomers/enantiomers of perfluorocarboxylic acids: Method development and detection in environmental samples.

    PubMed

    Naile, Jonathan E; Garrison, A Wayne; Avants, Jimmy K; Washington, John W

    2016-02-01

    Perfluoroalkyl substances are globally distributed in both urban and remote settings, and routinely are detected in wildlife, humans, and the environment. One of the most prominent and routinely detected perfluoroalkyl substances is perfluorooctanoic acid (PFOA), which has been shown to be toxic to both humans and animals. PFOA exists as both linear and branched isomers; some of the branched isomers are chiral. A novel GC-NCI-MS method was developed to allow for isomer/enantiomer separation, which was achieved using two columns working in tandem; a 30-m DB-5MS column and a 30-m BGB-172 Analytik column. Samples were derivatized with diazomethane to form methyl esters of the PFOA isomers. In standards, at least eight PFOA isomers were detected, of which at least four were enantiomers of chiral isomers; one chiral isomer (P3) was sufficiently separated to allow for enantiomer-fraction calculations. Soil, sediment and plant samples from contaminated locations in Alabama and Georgia were analyzed. P3 was observed in most of these environmental samples, and was non-racemic in at least one sediment, suggesting the possibility of chirally selective generation from precursors or enantioselective sorption. In addition, the ratio of P3/linear PFOA was inversely related to distance from source, which we suggest might reflect a higher sorption affinity for the P3 over the linear isomer. This method focuses on PFOA, but preliminary results suggest that it should be broadly applicable to other chiral and achiral perfluorocarboxylic acids (PFCAs); e.g., we detected several other homologous PFCA isomers in our PFCA standards and some environmental samples.

  12. Chromatographic preparation and kinetic analysis of interactions between tabun enantiomers and acetylcholinesterase.

    PubMed

    Tenberken, O; Thiermann, H; Worek, F; Reiter, G

    2010-06-02

    The easy accessibility to highly toxic OP (organophosphorus)-type chemical warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Reactivators (oximes) of inhibited AChE are a mainstay of treatment. However, the commercially available compounds, obidoxime and pralidoxime, are considered rather ineffective against various nerve agents, including tabun. OP-type chemical warfare agents include an asymmetrical P-atom and consist of at least two stereoisomers. Previous studies with the nerve agents sarin and soman showed marked differences between (-)- and (+)-P isomers regarding AChE inhibition and stability in biological matrices. Hence, stereoselectivity is a key parameter for the development of optimized treatment. In the present study, the tabun enantiomers were isolated by semi-preparative liquid-chromatography (LC) with offline analysis by GC-PCI-MS and final characterization of optical purity (99.98% (-)-tabun and 99.83% (+)-tabun) and specific optical rotation. The inhibition and reactivation kinetics of the tabun enantiomers were determined with human and swine AChE and the aging kinetics with human AChE. The results show a large difference in the inhibitory potency between (-)- and (+)-tabun. The determination of reactivation and aging kinetics indicates that both reactions are at least in part determined by the residual (-)-tabun contamination (0.17%) of the (+)-tabun preparation. These data provide further insight into the kinetic interactions between tabun enantiomers and AChE and may contribute to the development of more effective treatment options.

  13. Binding of naproxen enantiomers to human serum albumin studied by fluorescence and room-temperature phosphorescence

    NASA Astrophysics Data System (ADS)

    Lammers, Ivonne; Lhiaubet-Vallet, Virginie; Ariese, Freek; Miranda, Miguel A.; Gooijer, Cees

    2013-03-01

    The interaction of the enantiomers of the non-steroidal anti-inflammatory drug naproxen (NPX) with human serum albumin (HSA) has been investigated using fluorescence and phosphorescence spectroscopy in the steady-state and time-resolved mode. The absorption, fluorescence excitation, and fluorescence emission spectra of (S)-NPX and (R)-NPX differ in shape in the presence of HSA, indicating that these enantiomers experience a different environment when bound. In solutions containing 0.2 M KI, complexation with HSA results in a strongly increased NPX fluorescence intensity and a decreased NPX phosphorescence intensity due to the inhibition of the collisional interaction with the heavy atom iodide. Fluorescence intensity curves obtained upon selective excitation of NPX show 8-fold different slopes for bound and free NPX. No significant difference in the binding constants of (3.8 ± 0.6) × 105 M-1 for (S)-NPX and (3.9 ± 0.6) × 105 M-1 for (R)-NPX was found. Furthermore, the addition of NPX quenches the phosphorescence of the single tryptophan in HSA (Trp-214) based on Dexter energy transfer. The short-range nature of this mechanism explains the upward curvature of the Stern-Volmer plot observed for HSA: At low concentrations NPX binds to HSA at a distance from Trp-214 and no quenching occurs, whereas at high NPX concentrations the phosphorescence intensity decreases due to dynamic quenching by NPX diffusing into site I from the bulk solution. The dynamic quenching observed in the Stern-Volmer plots based on the longest phosphorescence lifetime indicates an overall binding constant to HSA of about 3 × 105 M-1 for both enantiomers.

  14. β-Cyclodextrin as the suitable molecular container for isopulegol enantiomers.

    PubMed

    Ceborska, Magdalena; Szwed, Kamila; Suwinska, Kinga

    2013-09-12

    Isopulegol, an insoluble in water and highly volatile compound, due to its neuroactive properties is a potentially important agent for medical applications. Formation of "host-guest" molecular complexes with cyclodextrins would lead to the increase of its water solubility and bioavailability. Interactions between native cyclodextrins (α, β and γ) and isopulegol enantiomers were studied in solution proving the formation of inclusion complexes for β- and γ-cyclodextrins. For the more stable complexes with β-cyclodextrin crystal structures were obtained showing the formation of molecular capsules forming molecular container able to accommodate two guest molecules.

  15. Biannual cycles of organochlorine pesticide enantiomers in arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2014-09-01

    Air samples collected during 1994-2000 at the Canadian arctic air monitoring station Alert (82°30' N, 62°20' W) were analyzed by enantiospecific gas chromatography - mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = quantities of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, <0.5 and >0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α-HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed biannual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed biannual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC + CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall vs. winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  16. Annual cycles of organochlorine pesticide enantiomers in Arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2015-02-01

    Air samples collected during 1994-2000 at the Canadian Arctic air monitoring station Alert (82°30' N, 62°20' W) were analysed by enantiospecific gas chromatography-mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = peak areas of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, < 0.5 and > 0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α -HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed annual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed annual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC+CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall versus winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  17. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    PubMed

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  18. [Synthesis and applications of chiral metal-organic framework in the selective separation of enantiomers].

    PubMed

    Qi, Xiaoyue; Li, Xianjiang; Bai, Yu; Liu, Huwei

    2016-01-01

    Chirality is a universal phenomenon in nature. Chiral separation is vitally important in drug development, agricultural chemistry, pharmacology, environmental science, biology and many other fields. Chiral metal-organic frameworks (MOFs) are a new group of porous materials with special topology and designable pore structures, as well as their high specific surface area, porosity, excellent thermal stability, solvent resistance, etc. Thus, chiral MOFs are promising with various applications in the field of analytical chemistry. This review summarizes the synthesis strategies of chiral MOFs and their applications in the selective separation of enantiomers, as well as related mechanism.

  19. Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers.

    PubMed

    Kasanen, J P; Pasanen, A L; Pasanen, P; Liesivuori, J; Kosma, V M; Alarie, Y

    1998-01-01

    To clarify the existence of a receptor protein for sensory irritants in trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha- and beta-pinene as models of nonreactive chemicals were evaluated for their potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes possess sensory irritation properties and also induced sedation and signs of anaesthesia but had no pulmonary irritation effects. According to the ratio of RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their potency as sensory irritant. Thus, for enantiomers with identical physicochemical properties, the estimated RD50 values are the same. In addition, although alpha- and beta-pinene do not have identical Po and Loil values, their estimated potencies are quite close. However, the experimental results showed that D-enantiomers of pinenes were the most potent as sensory irritants and a difference in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and 1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1 and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because its experimental RD50 was one-half of the estimated value while for D-beta-pinene those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times less potent than estimated. L-alpha-pinene was only slightly active although it was estimated to be as potent as D-alpha-pinene. The remarkable difference in potency between L-enantiometers is most likely due to a structural difference between alpha- and

  20. Two Unusual Polycyclic Polyprenylated Acylphloroglucinols, Including a Pair of Enantiomers from Garcinia multiflora.

    PubMed

    Fan, Yi-Min; Yi, Ping; Li, Yang; Yan, Chen; Huang, Tao; Gu, Wei; Ma, Yuan; Huang, Lie-Jun; Zhang, Jian-Xin; Yang, Chong-Lin; Li, Yan; Yuan, Chun-Mao; Hao, Xiao-Jiang

    2015-05-01

    Two polycyclic polyprenylated acylphloroglucinols, garcimulins A and B ((±)-1 and 2), including a pair of enantiomers with the unique caged tetracyclo[5.4.1.1(1,5).0(9,13)]tridecane skeleton were isolated from Garcinia multiflora. Their structures and absolute configurations were determined by extensive analysis of spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited cytotoxic activities against five human cancer cell lines in vitro (IC50 3.42-13.23 μM). The acidification of lysosomes in HeLa cell was obviously affected by compound 2.

  1. Chromatographic separation of phenylpropanol enantiomers on a quinidine carbamate-type chiral stationary phase

    SciTech Connect

    Asnin, Leonid; Guiochon, Georges A

    2005-07-01

    The retention and the separation of the enantiomers of 1-phenylpropanol (1PP), 2-phenylpropanol (2PP), and 3-chloro-1-phenylpropanol (3CPP) on silica-bonded quinidine carbamate under normal phase HPLC conditions were investigated. A relatively high selectivity of the stationary phase for 3CPP and 1PP ({alpha} {approx} 1.07-1.09) was achieved with eluents containing ethyl acetate as the polar modifier. These mobile phases were examined in detail. Based on the set of chromatographic and thermodynamic data collected, conclusions regarding the mechanism of enantioselectivity and the structure of the selector chiral center are made.

  2. Variation of Spectral Characteristics of Coelenteramide-Containing Fluorescent Protein from Obelia Longissima Exposed to Dimethyl Sulfoxide

    NASA Astrophysics Data System (ADS)

    Petrova, A. S.; Alieva, R. R.; Belogurova, N. V.; Tirranen, L. S.; Kudryasheva, N. S.

    2016-08-01

    Effect of dimethyl sulfoxide (DMSO), a widespread biomedical agent, on spectral-luminescent characteristics of coelenteramide-containing fluorescent protein - discharged obelin - is investigated. Contributions of violet and blue-green spectral components to fluorescence of discharged obelin are elucidated and characterized at different photoexcitation energies. Dependences of these contributions on the DMSO concentration are presented. Spectral changes are related to the destructive effect of DMSO on fluorescent protein and decreasing efficiency of proton transfer to electronically excited states of fluorophore.

  3. Decline in lymphatic filariasis transmission with annual mass drug administration using DEC with and without albendazole over a 10year period in India.

    PubMed

    Sunish, I P; Kalimuthu, M; Rajendran, R; Munirathinam, A; Ashok Kumar, V; Nagaraj, J; Tyagi, B K

    2015-02-01

    The National Programme for the Elimination of Lymphatic Filariasis is underway in the endemic districts of Tamil Nadu State, South India, since 2001. Annual mass drug administration (MDA) was carried out by the state health department to all eligible individuals. The impact of MDAs on transmission parameters was evaluated in 2 revenue blocks, viz, one with DEC alone and the other with a combination of albendazole. After 10 years with 6 annual MDAs, the transmission indices reached low levels in both treatment arms, but still persisted. However, the DEC alone arm showed higher transmission rates, compared to the DEC+ALB arm. Few villages which demonstrated persistent transmission need to be targeted with an additional control measure viz, vector control, to achieve LF elimination. It is evident from the 10 year period of the study that inclusion of albendazole along with DEC has significantly reduced the transmission indices to almost nil level, as compared to DEC alone.

  4. Validation of a Chiral Liquid Chromatographic Method for the Degradation Behavior of Flumequine Enantiomers in Mariculture Pond Water.

    PubMed

    Wang, Yan-Fei; Gao, Xiao-Feng; Jin, Huo-Xi; Wang, Yang-Guang; Wu, Wei-Jian; Ouyang, Xiao-Kun

    2016-09-01

    In this work, flumequine (FLU) enantiomers were separated using a Chiralpak OD-H column, with n-hexane-ethanol (20:80, v/v) as the mobile phase at a flow rate of 0.6 mL/min. Solid phase extraction (SPE) was used for cleanup and enrichment. The limit of detection, limit of quantitation, linearity, precision, and intra/interday variation of the chiral high-performance liquid chromatography (HPLC) method were determined. The developed method was then applied to investigate the degradation behavior of FLU enantiomers in mariculture pond water samples. The results showed that the degradation of FLU enantiomers under natural, sterile, or dark conditions was not enantioselective. Chirality 28:649-655, 2016. © 2016 Wiley Periodicals, Inc.

  5. Liquid chromatographic enantiomer separation of 1-naphthylamides of chiral acids using several amylose- and cellulose-derived chiral stationary phases.

    PubMed

    Islam, Md F; Adhikari, Suraj; Paik, Man-Jeong; Lee, Wonjae

    2017-03-01

    The liquid chromatographic enantiomer separation of various chiral acids as 1-naphthylamides was performed using several chiral stationary phases (CSPs). The CSPs used in this study were six covalently bonded and four coated type CSPs derived from amylose and cellulose derivatives as chiral selectors. The degree of enantioseparation is affected by the structure of chiral acids and the CSPs used, which have different chiral selectors and types of immobilization. For the enantiomer resolution of chiral acids as 1-naphthylamide derivatives, the performance of the coated type Lux Cellulose-1 was superior to those of the other CSPs, except for 2-aryloxypropionic acid derivatives. Owing to the strong ultraviolet absorbance of the 1-naphthyl group, the convenient analytical method developed and validated in this study could be expected to be very useful for the enantiomer separation of various chiral acids as 1-naphthylamide derivatives using polysaccharide-derived CSPs.

  6. Studies of a Novel Cysteine Sulfoxide Lyase from Petiveria alliacea: The First Heteromeric Alliinase1[W][OA

    PubMed Central

    Musah, Rabi A.; He, Quan; Kubec, Roman; Jadhav, Abhijit

    2009-01-01

    A novel alliinase (EC 4.4.1.4) was detected and purified from the roots of the Amazonian medicinal plant Petiveria alliacea. The isolated enzyme is a heteropentameric glycoprotein composed of two α-subunits (68.1 kD each), one β-subunit (56.0 kD), one γ-subunit (24.8 kD), and one δ-subunit (13.9 kD). The two α-subunits are connected by a disulfide bridge, and both α- and β-subunits are glycosylated. The enzyme has an isoelectric point of 4.78 and pH and temperature optima of 8.0 and approximately 52°C, respectively. Its activation energy with its natural substrate S-benzyl-l-cysteine sulfoxide is 64.6 kJ mol−1. Kinetic studies showed that both Km and Vmax vary as a function of substrate structure, with the most preferred substrates being the naturally occurring P. alliacea compounds S-benzyl-l-cysteine sulfoxide and S-2-hydroxyethyl-l-cysteine sulfoxide. The alliinase reacts with these substrates to produce S-benzyl phenylmethanethiosulfinate and S-(2-hydroxyethyl) 2-hydroxyethanethiosulfinate, respectively. PMID:19789290

  7. Determination of methiocarb and its degradation products, methiocarb sulfoxide and methiocarb sulfone, in bananas using QuEChERS extraction.

    PubMed

    Plácido, Alexandra; Paíga, Paula; Lopes, David H; Correia, Manuela; Delerue-Matos, Cristina

    2013-01-16

    The present work describes the development of an analytical method for the determination of methiocarb and its degradation products (methiocarb sulfoxide and methiocarb sulfone) in banana samples, using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure followed by liquid chromatography coupled to photodiode array detector (LC-PAD). Calibration curves were linear in the range of 0.5-10 mg L⁻¹ for all compounds studied. The average recoveries, measured at 0.1 mg kg⁻¹ wet weight, were 92.0 (RSD = 1.8%, n = 3), 84.0 (RSD = 3.9%, n = 3), and 95.2% (RSD = 1.9%, n = 3) for methiocarb sulfoxide, methiocarb sulfone, and methiocarb, respectively. Banana samples treated with methiocarb were collected from an experimental field. The developed method was applied to the analysis of 24 samples (peel and pulp) and to 5 banana pulp samples. Generally, the highest levels were found for methiocarb sulfoxide and methiocarb. Methiocarb sulfone levels were below the limit of quantification, except in one sample (not detected).

  8. Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

    PubMed

    Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

    2012-01-01

    Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

  9. Insights into function, catalytic mechanism, and fold evolution of selenoprotein methionine sulfoxide reductase B1 through structural analysis.

    PubMed

    Aachmann, Finn L; Sal, Lena S; Kim, Hwa-Young; Marino, Stefano M; Gladyshev, Vadim N; Dikiy, Alexander

    2010-10-22

    Methionine sulfoxide reductases protect cells by repairing oxidatively damaged methionine residues in proteins. Here, we report the first three-dimensional structure of the mammalian selenoprotein methionine sulfoxide reductase B1 (MsrB1), determined by high resolution NMR spectroscopy. Heteronuclear multidimensional spectra yielded NMR spectral assignments for the reduced form of MsrB1 in which catalytic selenocysteine (Sec) was replaced with cysteine (Cys). MsrB1 consists of a central structured core of two β-sheets and a highly flexible, disordered N-terminal region. Analysis of pH dependence of NMR signals of catalytically relevant residues, comparison with the data for bacterial MsrBs, and NMR-based structural analysis of methionine sulfoxide (substrate) and methionine sulfone (inhibitor) binding to MsrB1 at the atomic level reveal a mechanism involving catalytic Sec(95) and resolving Cys(4) residues in catalysis. The MsrB1 structure differs from the structures of Cys-containing MsrBs in the use of distal selenenylsulfide, residues needed for catalysis, and the mode in which the active form of the enzyme is regenerated. In addition, this is the first structure of a eukaryotic zinc-containing MsrB, which highlights the structural role of this metal ion bound to four conserved Cys. We integrated this information into a structural model of evolution of MsrB superfamily.

  10. A Randomized Controlled Trial of Increased Dose and Frequency of Albendazole with Standard Dose DEC for Treatment of Wuchereria bancrofti Microfilaremics in Odisha, India

    PubMed Central

    Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-01-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  11. Cerebral uptake of mefloquine enantiomers with and without the P-gp inhibitor elacridar (GF1210918) in mice

    PubMed Central

    de Lagerie, Sylvie Barraud; Comets, Emmanuelle; Gautrand, Céline; Fernandez, Christine; Auchere, Daniel; Singlas, Eric; Mentre, France; Gimenez, François

    2004-01-01

    Mefloquine is a chiral neurotoxic antimalarial agent showing stereoselective brain uptake in humans and rats. It is a substrate and an inhibitor of the efflux protein P-glycoprotein. We investigated the stereoselective uptake and efflux of mefloquine in mice, and the consequences of the combination with an efflux protein inhibitor, elacridar (GF120918) on its brain transport. Racemic mefloquine (25 mg kg−1) was administered intraperitoneally with or without elacridar (10 mg kg−1). Six to seven mice were killed at each of 11 time-points between 30 min and 168 h after administration. Blood and brain concentrations of mefloquine enantiomers were determined using liquid chromatography. A three-compartment model with zero-order absorption from the injection site was found to best represent the pharmacokinetics of both enantiomers in blood and brain. (−)Mefloquine had a lower blood and brain apparent volume of distribution and a lower efflux clearance from the brain, resulting in a larger brain/blood ratio compared to (+)mefloquine. Elacridar did not modify blood concentrations or the elimination rate from blood for either enantiomers. However, cerebral AUCinf of both enantiomers were increased, with a stronger effect on (+)mefloquine. The efflux clearance from the brain decreased for both enantiomers, with a larger decrease for (+)mefloquine. After administration of racemic mefloquine in mice, blood and brain pharmacokinetics are stereoselective, (+)mefloquine being excreted from brain more rapidly than its antipode, showing that mefloquine is a substrate of efflux proteins and that mefloquine enantiomers undergo efflux in a stereoselective manner. Moreover, pretreatment with elacridar reduced the brain efflux clearances with a more pronounced effect on (+)mefloquine. PMID:15023856

  12. Differential effects of omeprazole and lansoprazole enantiomers on aryl hydrocarbon receptor in human hepatocytes and cell lines.

    PubMed

    Novotna, Aneta; Srovnalova, Alzbeta; Svecarova, Michaela; Korhonova, Martina; Bartonkova, Iveta; Dvorak, Zdenek

    2014-01-01

    Proton pump inhibitors omeprazole and lansoprazole contain chiral sulfur atom and they are administered as a racemate, i.e. equimolar mixture of S- and R-enantiomers. The enantiopure drugs esomeprazole and dexlansoprazole have been developed and introduced to clinical practice due to their improved clinical and therapeutic properties. Since omeprazole and lansoprazole are activators of aryl hydrocarbon receptor (AhR) and inducers of CYP1A genes, we examined their enantiospecific effects on AhR-CYP1A pathway in human cancer cells and primary human hepatocytes. We performed gene reporter assays for transcriptional activity of AhR, RT-PCR analyses for CYP1A1/2 mRNAs, western blots for CYP1A1/2 proteins and EROD assay for CYP1A1/2 catalytic activity. Lansoprazole and omeprazole enantiomers displayed differential effects on AhR-CYP1A1/2 pathway. In general, S-enantiomers were stronger activators of AhR and inducers of CYP1A genes as compared to R-enantiomers in lower concentrations, i.e. 1-10 µM for lansoprazole and 10-100 µM for omeprazole. In contrast, R-enantiomers were stronger AhR activators and CYP1A inducers than S-enantiomers in higher concentrations, i.e. 100 µM for lansoprazole and 250 µM for omeprazole. In conclusion, we provide the first evidence of enantiospecific effects of omeprazole and lansoprazole on AhR signaling pathway.

  13. Dimethyl Sulfoxide Perturbs Cell Cycle Progression and Spindle Organization in Porcine Meiotic Oocytes

    PubMed Central

    Li, Xuan; Wang, Yan-Kui; Song, Zhi-Qiang; Du, Zhi-Qiang; Yang, Cai-Xia

    2016-01-01

    Meiotic maturation of mammalian oocytes is a precisely orchestrated and complex process. Dimethyl sulfoxide (DMSO), a widely used solvent, drug, and cryoprotectant, is capable of disturbing asymmetric cytokinesis of oocyte meiosis in mice. However, in pigs, DMSO’s effect on oocyte meiosis still remains unknown. We aimed to evaluate if DMSO treatment will affect porcine oocyte meiosis and the underlying molecular changes as well. Interestingly, we did not observe the formation of the large first polar body and symmetric division for porcine oocytes treated with DMSO, contrary to findings reported in mice. 3% DMSO treatment could inhibit cumulus expansion, increase nuclear abnormality, disturb spindle organization, decrease reactive oxygen species level, and elevate mitochondrial membrane potential of porcine oocytes. There was no effect on germinal vesicle breakdown rate regardless of DMSO concentration. 3% DMSO treatment did not affect expression of genes involved in spindle organization (Bub1 and Mad2) and apoptosis (NF-κB, Pten, Bcl2, Caspase3 and Caspase9), however, it significantly decreased expression levels of pluripotency genes (Oct4, Sox2 and Lin28) in mature oocytes. Therefore, we demonstrated that disturbed cumulus expansion, chromosome alignment, spindle organization and pluripotency gene expression could be responsible for DMSO-induced porcine oocyte meiotic arrest and the lower capacity of subsequent embryo development. Our results provide new insights on DMSO’s effect on porcine oocyte meiosis and raise safety concerns over DMSO’s usage on female reproduction in both farm animals and humans. PMID:27348312

  14. Methionine Sulfoxide Reductases Protect against Oxidative Stress in Staphylococcus aureus Encountering Exogenous Oxidants and Human Neutrophils

    PubMed Central

    Pang, Yun Yun; Schwartz, Jamie; Bloomberg, Sarah; Boyd, Jeffrey M; Horswill, Alexander R.; Nauseef, William M.

    2013-01-01

    To establish infection successfully, S. aureus must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence over the fate of S. aureus exposed to oxidants or PMN. We evaluated a mutant deficient in msrA1 and msrB for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of msrA1 in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of msr was studied by screening a library of two-component regulatory system (TCS) mutants for altered msr responses. Relative to the wild-type, bacteria deficient in Msr were more susceptible to oxidants and to PMN. Upregulation of staphylococcal msrA1 occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of msrA1. Modulation of msrA1 within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis. PMID:24247266

  15. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells

    PubMed Central

    Choi, S.; Sainz, B.; Corcoran, P.; Uprichard, S.; Jeong, H.

    2010-01-01

    1. The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). 2. The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. 3. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. 4. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model. PMID:19280519

  16. Dimethyl Sulfoxide Damages Mitochondrial Integrity and Membrane Potential in Cultured Astrocytes

    PubMed Central

    Yuan, Chan; Gao, Junying; Guo, Jichao; Bai, Lei; Marshall, Charles; Cai, Zhiyou; Wang, Linmei; Xiao, Ming

    2014-01-01

    Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO. PMID:25238609

  17. Dissolution of brominated epoxy resins by dimethyl sulfoxide to separate waste printed circuit boards.

    PubMed

    Zhu, Ping; Chen, Yan; Wang, Liangyou; Qian, Guangren; Zhang, Wei Jie; Zhou, Ming; Zhou, Jin

    2013-03-19

    Improved methods are required for the recycling of waste printed circuit boards (WPCBs). In this study, WPCBs (1-1.5 cm(2)) were separated into their components using dimethyl sulfoxide (DMSO) at 60 °C for 45 min and a metallographic microscope was used to verify their delamination. An increased incubation time of 210 min yielded a complete separation of WPCBs into their components, and copper foils and glass fibers were obtained. The separation time decreased with increasing temperature. When the WPCB size was increased to 2-3 cm(2), the temperature required for complete separation increased to 90 °C. When the temperature was increased to 135 °C, liquid photo solder resists could be removed from the copper foil surfaces. The DMSO was regenerated by rotary decompression evaporation, and residues were obtained. Fourier transform infrared spectroscopy (FT-IR), thermal analysis, nuclear magnetic resonance, scanning electron microscopy, and energy-dispersive X-ray spectroscopy were used to verify that these residues were brominated epoxy resins. From FT-IR analysis after the dissolution of brominated epoxy resins in DMSO it was deduced that hydrogen bonding may play an important role in the dissolution mechanism. This novel technology offers a method for separating valuable materials and preventing environmental pollution from WPCBs.

  18. Extracellular respiration of dimethyl sulfoxide by Shewanella oneidensis strain MR-1

    PubMed Central

    Gralnick, Jeffrey A.; Vali, Hojatollah; Lies, Douglas P.; Newman, Dianne K.

    2006-01-01

    Shewanella species are renowned for their respiratory versatility, including their ability to respire poorly soluble substrates by using enzymatic machinery that is localized to the outside of the cell. The ability to engage in “extracellular respiration” to date has focused primarily on respiration of minerals. Here, we identify two gene clusters in Shewanella oneidensis strain MR-1 that each contain homologs of genes required for metal reduction and genes that are predicted to encode dimethyl sulfoxide (DMSO) reductase subunits. Molecular and genetic analyses of these clusters indicate that one (SO1427–SO1432) is required for anaerobic respiration of DMSO. We show that DMSO respiration is an extracellular respiratory process through the analysis of mutants defective in type II secretion, which is required for transporting proteins to the outer membrane in Shewanella. Moreover, immunogold labeling of DMSO reductase subunits reveals that they reside on the outer leaflet of the outer membrane under anaerobic conditions. The extracellular localization of the DMSO reductase in S. oneidensis suggests these organisms may perceive DMSO in the environment as an insoluble compound. PMID:16537430

  19. Crystallization of Ice in Aqueous Solutions of Glycerol and Dimethyl Sulfoxide. 1. A Comparison of Mechanisms

    PubMed

    Hey; Macfarlane

    1996-04-01

    The crystallization of ice from aqueous solutions of glycerol and dimethyl sulfoxide (Me2SO) has been studied using differential scanning calorimetry. In particular, the ice crystallization behavior of glycerol and Me2SO solutions containing approximately the same mole percent solute concentration (i.e., approximately 16 mol%) has been compared. These solutions (45 w/w% Me2SO (15.9 mol%) and 50 w/w% glycerol (16.4 mol%)) were shown to exhibit markedly different ice crystallization properties. For example, the peak homogeneous nucleation temperature of the Me2SO solution was observed to be 3°C above Tg, whereas the peak homogeneous nucleation temperature of the glycerol solution was shown to be 20°C above Tg. Further, the 50 w/w% glycerol solution was shown to devitrify at temperatures close to those of the peak nucleation rate, whereas the Me2SO solution was found to devitrify at temperatures much higher than the peak nucleation temperature. This, along with evidence from emulsion-based calorimetry experiments, indicates that the nucleation leading to devitrification in 45 w/w% Me2SO solutions is largely heterogeneous in nature.

  20. Rice starch, amylopectin, and amylose: molecular weight and solubility in dimethyl sulfoxide-based solvents.

    PubMed

    Zhong, Fang; Yokoyama, Wallace; Wang, Qian; Shoemaker, Charles F

    2006-03-22

    Dimethyl sulfoxide (DMSO), with either 50 mM LiBr, 10% water, or both, was used as solvent for multi-angle laser-light scattering (MALLS) batch mode analysis of rice starch, and amylopectin and amylose weight-average molecular weight (Mw). DMSO/50 mM LiBr was a better solvent for these measurements than was DMSO/10% water, based on this solvent's ability to dissolve starch and to reduce the size of starch aggregates. Starch concentration decreased and amylose:amylopectin ratio increased when starch suspended in DMSO was centrifuged or filtered prior to size-exclusion chromatography (SEC)-MALLS analysis. A higher amylose:amylopectin ratio made starch more soluble, and the higher this ratio, the lower the Mw of eluted amylopectin. For SEC analysis of Mw, fractions of starch amylopectin and amylose dispersed in DMSO-based solvents yielded better results than starch dispersed directly into the solvents, because dispersion of these fractions decreased starch aggregation. When these two starch components were fractionated and then dissolved separately in DMSO/50 mM LiBr, the Mw of dispersed amylopectin ranged from 40 to 50 million, and that of amylose was ca. 3 million, whereas starch from three rice varieties of varying amylose content ranged from 60 to 130 million. We recommend that SEC evaluation of amylopectin and amylose be accomplished with fractionated samples as in this study; such evaluations were superior to evaluations of natural mixtures of amylopectin and amylose.

  1. A catalase-peroxidase for oxidation of β-lactams to their (R)-sulfoxides.

    PubMed

    Sangar, Shefali; Pal, Mohan; Moon, Lomary S; Jolly, Ravinder S

    2012-07-01

    In this communication we report for the first time a biocatalytic method for stereoselective oxidation of β-lactams, represented by penicillin-G, penicillin-V and cephalosporin-G to their (R)-sulfoxides. The method involves use of a bacterium, identified as Bacillus pumilis as biocatalyst. The enzyme responsible for oxidase activity has been purified and characterized as catalase-peroxidase (KatG). KatG of B. pumilis is a heme containing protein showing characteristic heme spectra with soret peak at 406 nm and visible peaks at 503 and 635 nm. The major properties that distinguish B. pumilis KatG from other bacterial KatGs are (i) it is a monomer and contains one heme per monomer, whereas KatGs of other bacteria are dimers or tetramers and have low heme content of about one per dimer or two per tetramer and (ii) its 12-residue, N-terminal sequence obtained by Edman degradation did not show significant similarity with any of known KatGs.

  2. Cryopreservation of buffy-coat-derived platelet concentrates in dimethyl sulfoxide and platelet additive solution.

    PubMed

    Johnson, L N; Winter, K M; Reid, S; Hartkopf-Theis, T; Marks, D C

    2011-04-01

    Platelets prepared in plasma can be frozen in 6% dimethyl sulfoxide (Me(2)SO) and stored for extended periods at -80°C. The aim of this study was to reduce the plasma present in the cryopreserved product, by substituting plasma with platelet additive solution (PAS; SSP+), whilst maintaining in vitro platelet quality. Buffy coat-derived pooled leukoreduced platelet concentrates were frozen in a mixture of SSP+, plasma and 6% Me(2)SO. The platelets were concentrated, to avoid post-thaw washing, and frozen at -80°C. The cryopreserved platelet units (n=9) were rapidly thawed at 37°C, reconstituted in 50% SSP+/plasma and stored at 22°C. Platelet recovery and quality were examined 1 and 24h post-thaw and compared to the pre-freeze samples. Upon thawing, platelet recovery ranged from 60% to 80%. However, there were differences between frozen and liquid-stored platelets, including a reduction in aggregation in response to ADP and collagen; increased CD62P expression; decreased viability; increased apoptosis and some loss of mitochondrial membrane integrity. Some recovery of these parameters was detected at 24h post-thaw, indicating an extended shelf-life may be possible. The data suggests that freezing platelets in 6% Me(2)SO and additive solution produces acceptable in vitro platelet quality.

  3. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

    PubMed Central

    Gleichman, Julia S.; Kramer, Matthew D.; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M.; Steyger, Peter S.; Cotanche, Douglas A.; Matsui, Jonathan I.

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO. PMID:23383324

  4. Oxidation of dimethyl sulfide to dimethyl sulfoxide by phototrophic purple bacteria

    SciTech Connect

    Zeyer, J.; Eicher, P.; Wakeham, S.G.; Schwarzenbach, R.P.

    1987-09-01

    Enrichment cultures of phototrophic purple bacteria rapidly oxidized up to 10 mM dimethyl sulfide (DMS) to dimethyl sulfoxide (DMSO). DMSO was qualitatively identified by proton nuclear magnetic resonance. By using a biological assay, DMSO was always quantitatively recovered from the culture media. DMS oxidation was not detected in cultures incubated in the dark, and it was slow in cultures exposed to full daylight. Under optimal conditions, the second-order rate constant for DMS oxidation was 6 day/sup -1/ mg of protein/sup -1/ ml/sup -1/. The rate constant was reduced in the presence of high concentration of sulfide (>1 mM), but was not affected by the addition of acetate. DMS was also oxidized to DMSO by a pure strain (tentatively identified as a Thiocystis sp.) isolated from the enrichment cultures. DMS supported growth of the enrichment cultures and of the pure strain by serving as an electron source for photosynthesis. A determination of the amount of protein produced in the cultures and an estimation of the electron balance suggested that the two electrons liberated during the oxidation of DMS to DMSO were quantitatively used to reduce carbon dioxide to biomass. The oxidation of DMS by phototrophic purple bacteria may be an important source of DMSO detected in anaerobic ponds and marshes.

  5. Specific reduction of N,N-dimethylnitrosamine mutagenicity in Drosophila melanogaster by dimethyl sulfoxide

    SciTech Connect

    Brodberg, R.K.; Mitchell, M.J.; Smith, S.L.; Woodruff, R.C.

    1988-01-01

    Dimethyl sulfoxide (DMSO) used as a solvent has been observed to complicate mutagenicity screens by interacting with tested chemicals to yield false positive or negatives. The authors have used DMSO as a solvent in the Drosophila melanogaster recessive sex-linked lethal mutation assay and find that it reduces, but does not abolish, the detectable mutagenicity of N,N-dimethylnitrosamine (DMN). Its use as a solvent with procarbazine, another promutagen, shows no effect on mutagenicity in Drosophila. DMSO does not exhibit a general inhibitory action on microsome activity when ecdysone 20-monooxygenase activity is used as a measure of cytochrome P-450 activity. They were unable to detect the low DMN demethylase activity in the strain used. Hence, the inhibitory effect of DMSO in Drosophila at both the physiological and biological level appears to be limited and not general in action. Because DMN and DMSO are similar in structure, it is possible that DMSO is interacting with a DMN demethylase in Drosophila. This might lead to a reduction in the conversion of DMN to a mutagen. Consequently, from the results of this study and others DMSO should be used cautiously as a solvent in Drosophila mutagen screening.

  6. A model to predict the permeation kinetics of dimethyl sulfoxide in articular cartilage.

    PubMed

    Yu, Xiaoyi; Chen, Guangming; Zhang, Shaozhi

    2013-02-01

    Cryopreservation of articular cartilage (AC) has excited great interest due to the practical surgical importance of this tissue. Characterization of permeation kinetics of cryoprotective agents (CPA) in AC is important for designing optimal CPA addition/removal protocols to achieve successful cryopreservation. Permeation is predominantly a mass diffusion process. Since the diffusivity is a function of temperature and concentration, analysis of the permeation problem would be greatly facilitated if a predictive method were available. This article describes, a model that was developed to predict the permeation kinetics of dimethyl sulfoxide (DMSO) in AC. The cartilage was assumed as a porous medium, and the effect(s) of composition and thermodynamic nonideality of the DMSO solution were considered in model development. The diffusion coefficient was correlated to the infinite dilution coefficients through a binary diffusion thermodynamic model. The UNIFAC model was used to evaluate the activity coefficient, the Vignes equation was employed to estimate the composition dependence of the diffusion coefficient, and the Siddiqi-Lucas correlation was applied to determine the diffusion coefficients at infinite dilution. Comparisons of the predicted overall DMSO uptake by AC with the experimental data over wide temperature and concentration ranges [1~37°C, 10~47% (w/w)] show that the model can accurately describe the permeation kinetics of DMSO in AC [coefficient of determination (R(2)): 0.961~0.996, mean relative error (MRE): 2.2~9.1%].

  7. Two highly homologous methionine sulfoxide reductase A from tomato (Solanum lycopersicum), exhibit distinct catalytic properties.

    PubMed

    Dai, Changbo; Han, Woong; Wang, Myeong-Hyeon

    2012-04-01

    E4, which is a fruit-ripening gene that is strongly induced by ethylene, has been reported to be a member of the methionine sulfoxide reductase A (MSRA) gene. In the present study, we determined for the first time the enzymatic activity and delineated the catalytic mechanism of the E4 protein via site-directed mutagenesis. The disulfide intermolecular cross-linking, kinetics parameter, thiol content titration analysis of wild-type and mutated E4 proteins revealed that the cysteine at position 37 (Cys-37) was the key catalytic residue, and Cys-194, but not Cys-180 served as the first recycling Cys in the thioredoxin (Trx)-dependent regeneration system. In addition, the SlMSRA2 protein, which was encoded by another MSRA gene, shared high similarity with the E4 protein and was truncated at the C-terminus. The wild-type and mutated SlMSRA2 enzymes had similar activities compared to the E4 protein using DTT as a reductant, but showed extremely low activities in the Trx-dependent reduction system. Our results indicated that E4 and SlMSRA2 proteins might exhibit distinct catalytic mechanisms.

  8. Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress

    PubMed Central

    Suzuki, Satoko; Kodera, Yoshio; Saito, Tatsuya; Fujimoto, Kazumi; Momozono, Akari; Hayashi, Akinori; Kamata, Yuji; Shichiri, Masayoshi

    2016-01-01

    Oxidative stress contributes to the pathophysiology of a variety of diseases, and circulating biomarkers of its severity remains a topic of great interest for researchers. Our peptidomic strategy enables accurate and reproducible analysis of circulating proteins/peptides with or without post-translational modifications. Conventional wisdom holds that hydrophobic methionines exposed to an aqueous environment or experimental handling procedures are vulnerable to oxidation. However, we show that the mass spectra intensity ratio of oxidized to non-oxidized methionine residues in serum tryptic proteins can be accurately quantified using a single drop of human serum and give stable and reproducible results. Our data demonstrate that two methionine residues in serum albumin (Met-111 and Met-147) are highly oxidized to methionine sulfoxide in patients with diabetes and renal failure and in healthy smokers versus non-smoker controls. This label-free mass spectrometry approach to quantify redox changes in methionine residues should facilitate the identification of additional circulating biomarkers suitable for predicting the development or progression of human diseases. PMID:27929071

  9. Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain.

    PubMed

    Hoang, Ba X; Tran, Dao M; Tran, Hung Q; Nguyen, Phuong T M; Pham, Tuan D; Dang, Hong V T; Ha, Trung V; Tran, Hau D; Hoang, Cuong; Luong, Khue N; Shaw, D Graeme

    2011-01-01

    Pain is a major concern of cancer patients and a significant problem for therapy. Pain can become a predominant symptom in advanced cancers. In this open-label clinical study, the authors have treated 26 cancer patients who have been declared as terminal without the option of conventional treatment. These patients suffered from high levels of pain that was poorly managed by all available interventional approaches recommended by World Health Organization (WHO) guideline. The results indicate that intravenous infusion of dimethyl sulfoxide (DMSO) and sodium bicarbonate (SB) solution can be a viable, effective, and safe treatment for refractory pain in cancer patients. These patients had pain due to the disease progression and complication of chemotherapy and radiation. Moreover, the preliminary clinical outcome of 96-day follow-up suggests that the application of DMSO and SB solution intravenously could lead to better quality of life for patients with nontreatable terminal cancers. The data of this clinical observation indicates that further research and application of the DMSO and SB combination may help the development of an effective, safe, and inexpensive therapy to manage cancer pain.

  10. Ion transport properties of magnesium bromide/dimethyl sulfoxide non-aqueous liquid electrolyte

    PubMed Central

    Sheha, E.

    2015-01-01

    Nonaqueous liquid electrolyte system based dimethyl sulfoxide DMSO and magnesium bromide (MgBr2) is synthesized via ‘Solvent-in-Salt’ method for the application in magnesium battery. Optimized composition of MgBr2/DMSO electrolyte exhibits high ionic conductivity of 10−2 S/cm at ambient temperature. This study discusses different concentrations from 0 to 5.4 M of magnesium salt, representing low, intermediate and high concentrations of magnesium salt which are examined in frequency dependence conductivity studies. The temperature dependent conductivity measurements have also been carried out to compute activation energy (Ea) by least square linear fitting of Arrhenius plot: ‘log σ − 1/T. The transport number of Mg2+ ion determined by means of a combination of d.c. and a.c. techniques is ∼0.7. A prototype cell was constructed using nonaqueous liquid electrolyte with Mg anode and graphite cathode. The Mg/graphite cell shows promising cycling. PMID:26843967

  11. The Proline Enamine Formation Pathway Revisited in Dimethyl Sulfoxide: Rate Constants Determined via NMR.

    PubMed

    Haindl, Michael H; Hioe, Johnny; Gschwind, Ruth M

    2015-10-14

    Enamine catalysis is a fundamental activation mode in organocatalysis and can be successfully combined with other catalytic methods, e.g., photocatalysis. Recently, the elusive enamine intermediates were detected, and their stabilization modes were revealed. However, the formation pathway of this central organocatalytic intermediate is still a matter of dispute, and several mechanisms involving iminium and/or oxazolidinone are proposed. Here, the first experimentally determined rate constants and rates of enamine formation are presented using 1D selective exchange spectroscopy (EXSY) buildup curves and initial rate approximation. The trends of the enamine formation rates from exo-oxazolidinones and endo-oxazolidinones upon variation of the proline and water concentrations as well as the nucelophilic/basic properties of additives are investigated together with isomerization rates of the oxazolidinones. These first kinetic data of enamine formations in combination with theoretical calculations reveal the deprotonation of iminium intermediates as the dominant pathway in dimethyl sulfoxide (DMSO). The dominant enamine formation pathway varies according to the experimental conditions, e.g., the presence and strength of basic additives. The enamine formation is zero-order in proline and oxazolidinones, which excludes the direct deprotonation of oxazolidinones via E2 mechanism. The nucleophilicity of the additives influences only the isomerization rates of the oxazolidinones and not the enamine formation rates, which excludes a nucleophile-assisted anti elimination of oxazolidinones as a major enamine formation pathway.

  12. Extracellular respiration of dimethyl sulfoxide by Shewanella oneidensis strain MR-1.

    PubMed

    Gralnick, Jeffrey A; Vali, Hojatollah; Lies, Douglas P; Newman, Dianne K

    2006-03-21

    Shewanella species are renowned for their respiratory versatility, including their ability to respire poorly soluble substrates by using enzymatic machinery that is localized to the outside of the cell. The ability to engage in "extracellular respiration" to date has focused primarily on respiration of minerals. Here, we identify two gene clusters in Shewanella oneidensis strain MR-1 that each contain homologs of genes required for metal reduction and genes that are predicted to encode dimethyl sulfoxide (DMSO) reductase subunits. Molecular and genetic analyses of these clusters indicate that one (SO1427-SO1432) is required for anaerobic respiration of DMSO. We show that DMSO respiration is an extracellular respiratory process through the analysis of mutants defective in type II secretion, which is required for transporting proteins to the outer membrane in Shewanella. Moreover, immunogold labeling of DMSO reductase subunits reveals that they reside on the outer leaflet of the outer membrane under anaerobic conditions. The extracellular localization of the DMSO reductase in S. oneidensis suggests these organisms may perceive DMSO in the environment as an insoluble compound.

  13. NIa-pro of Papaya ringspot virus interacts with papaya methionine sulfoxide reductase B1.

    PubMed

    Gao, Le; Shen, Wentao; Yan, Pu; Tuo, Decai; Li, Xiaoying; Zhou, Peng

    2012-12-05

    A chloroplast-localized papaya methionine sulfoxide reductase B1 (PaMsrB1) interacting with Papaya ringspot virus (PRSV) NIa-Pro was identified using a Sos recruitment two-hybrid system (SRS). SRS analysis of several deletion mutants of PRSV NIa-Pro and PaMsrB1 demonstrated that the C-terminal (residues 133-239) fragment of PRSV NIa-Pro and residues 112-175 of PaMsrB1 were necessary for this interaction between PRSV NIa-Pro and PaMsrB1. MsrB1 can repair Met-oxidized proteins damaged by reactive oxygen species (ROS). We confirmed that PRSV infection leads to ROS accumulation and a slight upregulation of level PaMsrB1 mRNA in papaya. This interaction between PaMsrB1 with PRSV NIa-Pro may disturb the import of PaMsrB1 into the chloroplasts. These results suggest that this specific interaction could interfere with PaMsrB1 into the chloroplasts to scavenge ROS caused by PRSV infection. This may be a novel mechanism of PRSV towards the host defense.

  14. Solvent stimulated actuation of polyurethane-based shape memory polymer foams using dimethyl sulfoxide and ethanol

    NASA Astrophysics Data System (ADS)

    Boyle, A. J.; Weems, A. C.; Hasan, S. M.; Nash, L. D.; Monroe, M. B. B.; Maitland, D. J.

    2016-07-01

    Solvent exposure has been investigated to trigger actuation of shape memory polymers (SMPs) as an alternative to direct heating. This study aimed to investigate the feasibility of using dimethyl sulfoxide (DMSO) and ethanol (EtOH) to stimulate polyurethane-based SMP foam actuation and the required solvent concentrations in water for rapid actuation of hydrophobic SMP foams. SMP foams exhibited decreased T g when submerged in DMSO and EtOH when compared to water submersion. Kinetic DMA experiments showed minimal or no relaxation for all SMP foams in water within 30 min, while SMP foams submerged in EtOH exhibited rapid relaxation within 1 min of submersion. SMP foams expanded rapidly in high concentrations of DMSO and EtOH solutions, where complete recovery over 30 min was observed in DMSO concentrations greater than 90% and in EtOH concentrations greater than 20%. This study demonstrates that both DMSO and EtOH are effective at triggering volume recovery of polyurethane-based SMP foams, including in aqueous environments, and provides promise for use of this actuation technique in various applications.

  15. Effect of Dimethyl Sulfoxide and Melatonin on the Isolation of Human Primary Hepatocytes.

    PubMed

    Solanas, Estela; Sostres, Carlos; Serrablo, Alejandro; García-Gil, Agustín; García, Joaquín J; Aranguren, Francisco J; Jiménez, Pilar; Hughes, Robin D; Serrano, María T

    2015-01-01

    The availability of fully functional human hepatocytes is critical for progress in human hepatocyte transplantation and the development of bioartificial livers and in vitro liver systems. However, the cell isolation process impairs the hepatocyte status and determines the number of viable cells that can be obtained. This study aimed to evaluate the effects of using dimethyl sulfoxide (DMSO) and melatonin in the human hepatocyte isolation protocol. Human hepatocytes were isolated from liver pieces resected from 10 patients undergoing partial hepatectomy. Each piece was dissected into 2 equally sized pieces and randomized, in 5 of 10 isolations, to perfusion with 1% DMSO-containing perfusion buffer or buffer also containing 5 mM melatonin using the 2-step collagenase perfusion technique (experiment 1), and in the other 5 isolations to standard perfusion or perfusion including 1% DMSO (experiment 2). Tissues perfused with DMSO yielded 70.6% more viable hepatocytes per gram of tissue (p = 0.076), with a 26.1% greater albumin production (p < 0.05) than those perfused with control buffer. Melatonin did not significantly affect (p > 0.05) any of the studied parameters, but cell viability, dehydrogenase activity, albumin production, urea secretion, and 7-ethoxycoumarin O-deethylase activity were slightly higher in cells isolated with melatonin-containing perfusion buffer compared to those isolated with DMSO. In conclusion, addition of 1% DMSO to the hepatocyte isolation protocol could improve the availability and functionality of hepatocytes for transplantation, but further studies are needed to clarify the mechanisms involved.

  16. Factors affecting degradation of dimethyl sulfoxide (DMSO) by fluidized-bed Fenton process.

    PubMed

    Bellotindos, Luzvisminda M; Lu, Meng-Hsuan; Methatham, Thanakorn; Lu, Ming-Chun

    2014-12-01

    In this study, the target compound is dimethyl sulfoxide (DMSO), which is used as a photoresist stripping solvent in the semiconductor and thin-film transistor liquid crystal display (TFT-LCD) manufacturing processes. The effects of the operating parameters (pH, Fe(2+) and H2O2 concentrations) on the degradation of DMSO in the fluidized-bed Fenton process were examined. This study used the Box-Behnken design (BBD) to investigate the optimum conditions of DMSO degradation. The highest DMSO removal was 98 % for pH 3, when the H2O2 to Fe(2+) molar ratio was 12. At pH 2 and 4, the highest DMSO removal was 82 %, when the H2O2 to Fe(2+) molar ratio was 6.5. The correlation of DMSO removal showed that the effect of the parameters on DMSO removal followed the order Fe(2+) > H2O2 > pH. From the BBD prediction, the optimum conditions were pH 3, 5 mM of Fe(2+), and 60 mM of H2O2. The difference between the experimental value (98 %) and the predicted value (96 %) was not significant. The removal efficiencies of DMSO, chemical oxygen demand (COD), total organic carbon (TOC), and iron in the fluidized-bed Fenton process were higher than those in the traditional Fenton process.

  17. X-Ray Absorption Spectroscopic Characterization of the Molybdenum Site of 'Escherichia Coli' Dimethyl Sulfoxide Reductase

    SciTech Connect

    George, G.N.; Doonan, C.J.; Rothery, R.A.; Boroumand, N.; Weiner, J.H.; /Saskatchewan U. /Alberta U.

    2007-07-09

    Structural studies of dimethyl sulfoxide (DMSO) reductases were hampered by modification of the active site during purification. We report an X-ray absorption spectroscopic analysis of the molybdenum active site of Escherichia coli DMSO reductase contained within its native membranes. The enzyme in these preparations is expected to be very close to the form found in vivo. The oxidized active site was found to have four Mo-S ligands at 2.43 angstroms, one Mo=O at 1.71 angstroms, and a longer Mo-O at 1.90 angstroms. We conclude that the oxidized enzyme is a monooxomolybdenum(VI) species coordinated by two molybdopterin dithiolenes and a serine. The bond lengths determined for E. coli DMSO reductase are very similar to those determined for the well-characterized Rhodobacter sphaeroides DMSO reductase, suggesting similar active site structures for the two enzymes. Furthermore, our results suggest that the form found in vivo is the monooxobis(molybdopterin) species.

  18. Dimethyl sulfoxide (DMSO) exacerbates cisplatin-induced sensory hair cell death in zebrafish (Danio rerio).

    PubMed

    Uribe, Phillip M; Mueller, Melissa A; Gleichman, Julia S; Kramer, Matthew D; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M; Steyger, Peter S; Cotanche, Douglas A; Matsui, Jonathan I

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.

  19. Comparative study of halogen- and hydrogen-bond interactions between benzene derivatives and dimethyl sulfoxide.

    PubMed

    Zheng, Yan-Zhen; Deng, Geng; Zhou, Yu; Sun, Hai-Yuan; Yu, Zhi-Wu

    2015-08-24

    The halogen bond, similar to the hydrogen bond, is an important noncovalent interaction and plays important roles in diverse chemistry-related fields. Herein, bromine- and iodine-based halogen-bonding interactions between two benzene derivatives (C6 F5 Br and C6 F5 I) and dimethyl sulfoxide (DMSO) are investigated by using IR and NMR spectroscopy and ab initio calculations. The results are compared with those of interactions between C6 F5 Cl/C6 F5 H and DMSO. First, the interaction energy of the hydrogen bond is stronger than those of bromine- and chlorine-based halogen bonds, but weaker than iodine-based halogen bond. Second, attractive energies depend on 1/r(n) , in which n is between three and four for both hydrogen and halogen bonds, whereas all repulsive energies are found to depend on 1/r(8.5) . Third, the directionality of halogen bonds is greater than that of the hydrogen bond. The bromine- and iodine-based halogen bonds are strict in this regard and the chlorine-based halogen bond only slightly deviates from 180°. The directional order is iodine-based halogen bond>bromine-based halogen bond>chlorine-based halogen bond>hydrogen bond. Fourth, upon the formation of hydrogen and halogen bonds, charge transfers from DMSO to the hydrogen- and halogen-bond donors. The CH3 group contributes positively to stabilization of the complexes.

  20. Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system.

    PubMed

    Hanslick, Jennifer L; Lau, Karen; Noguchi, Kevin K; Olney, John W; Zorumski, Charles F; Mennerick, Steven; Farber, Nuri B

    2009-04-01

    Dimethyl sulfoxide (DMSO) is a solvent that is routinely used as a cryopreservative in allogous bone marrow and organ transplantation. We exposed C57Bl/6 mice of varying postnatal ages (P0-P30) to DMSO in order to study whether DMSO could produce apoptotic degeneration in the developing CNS. DMSO produced widespread apoptosis in the developing mouse brain at all ages tested. Damage was greatest at P7. Significant elevations above the background rate of apoptosis occurred at the lowest dose tested, 0.3 ml/kg. In an in vitro rat hippocampal culture preparation, DMSO produced neuronal loss at concentrations of 0.5% and 1.0%. The ability of DMSO to damage neurons in dissociated cultures indicates that the toxicity likely results from a direct cellular effect. Because children, who undergo bone marrow transplantation, are routinely exposed to DMSO at doses higher than 0.3 ml/kg, there is concern that DMSO might be producing similar damage in human children.

  1. Molecular structure and adsorption of dimethyl sulfoxide at the surface of aqueous solutions

    SciTech Connect

    Allen, H.C.; Gragson, D.E.; Richmond, G.L.

    1999-01-28

    Surface vibrational sum frequency generation (VSFG) spectroscopy complemented with surface tension measurements has been utilized to probe the air/dimethyl sulfoxide (DMSO) interface as a function of DMSO concentration in water. For the neat DMSO surface, the DMSO methyl groups extend away from the liquid phase and VSFG polarization studies show that the methyl transition dipole moments of pure DMSO are on average oriented a maximum of 55{degree} from the surface normal. A blue shift of the methyl symmetric stretch is observed with decreasing DMSO concentration and attributed to an electronic interaction between the sulfur and the methyl groups of DMSO. From surface tension data of the aqueous DMSO system, it is shown the DMSO number densities are higher at the surface of DMSO-water solutions relative to bulk DMSO concentrations revealing surface partitioning effects. Structural changes of surface DMSO are discussed in terms of monomers, dimers, and clusters which could account for the large differences in VSFG intensities and surface number densities. From surface tension measurements and utilizing DMSO activities, {Delta}G{sub ads}{sup 0} is calculated to be {minus}19.8 ({+-}0.4) kJ/mol.

  2. Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes.

    PubMed

    Nardid, Oleg A; Schetinskey, Miroslav I; Kucherenko, Yuliya V

    2013-03-01

    Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline solutions of: 40.3 ± 3.9% for K+, 35.4 ± 3.1% for Ca2+ and 47.4 ± 1.9% for NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na+ and Ca2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed.

  3. Dimethyl sulfoxide damages mitochondrial integrity and membrane potential in cultured astrocytes.

    PubMed

    Yuan, Chan; Gao, Junying; Guo, Jichao; Bai, Lei; Marshall, Charles; Cai, Zhiyou; Wang, Linmei; Xiao, Ming

    2014-01-01

    Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO.

  4. Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta.

    PubMed

    Kaneda, Takeharu; Sasaki, Noriyasu; Urakawa, Norimoto; Shimizu, Kazumasa

    2016-01-01

    This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 μmol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-NG-nitroarginine methyl ester (L-NAME, 100 μmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 μmol/l) increased cGMP contents, significantly and L-NAME (100 μmol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium-denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+]i level. In PE-precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta.

  5. Investigation of the interaction of dimethyl sulfoxide with lipid membranes by small-angle neutron scattering

    SciTech Connect

    Gorshkova, J. E. Gordeliy, V. I.

    2007-05-15

    The influence of dimethyl sulfoxide (CH{sub 3}){sub 2}SO (DMSO) on the structure of membranes of 1,2-dimiristoyl-sn-glycero-3-phosphatidylcholine (DMPC) in an excess of a water-DMSO solvent is investigated over a wide range of DMSO molar concentrations 0.0 {<=} X{sub DMSO} {<=} 1.0 at temperatures T = 12.5 and 55 deg. C. The dependences of the repeat distance d of multilamellar membranes and the thickness d{sub b} of single vesicles on the molar concentration X{sub DMSO} in the L{sub {beta}}{sub '} gel and L{sub {alpha}} liquid-crystalline phases are determined by small-angle neutron scattering. The intermembrane distance d{sub s} is determined from the repeat distance d and the membrane thickness d{sub b}. It is shown that an increase in the molar concentration X{sub DMSO} leads to a considerable decrease in the intermembrane distance and that, at X{sub DMSO} = 0.4, the neighboring membranes are virtually in steric contact with each other. The use of the deuterated phospholipid (DMSO-D6) and the contrast variation method makes it possible, for the first time, to determine the number of DMSO molecules strongly bound to the membrane.

  6. Dimethyl sulfoxide attenuates hydrogen peroxide-induced injury in cardiomyocytes via heme oxygenase-1.

    PubMed

    Man, Wang; Ming, Ding; Fang, Du; Chao, Liang; Jing, Cang

    2014-06-01

    The antioxidant property of dimethyl sulfoxide (DMSO) was formerly attributed to its direct effects. Our former study showed that DMSO is able to induce heme oxygenase-1 (HO-1) expression in endothelial cells, which is a potent antioxidant enzyme. In this study, we hypothesized that the antioxidant effects of DMSO in cardiomyocytes are mediated or partially mediated by increased HO-1 expression. Therefore, we investigated whether DMSO exerts protective effects against H2 O2 -induced oxidative damage in cardiomyocytes, and whether HO-1 is involved in DMSO-imparted protective effects, and we also explore the underlying mechanism of DMSO-induced HO-1 expression. Our study demonstrated that DMSO pretreatment showed a cytoprotective effect against H2 O2 -induced oxidative damage (impaired cell viability, increased apopototic cells rate and caspase-3 level, and increased release of LDH and CK) and this process is partially mediated by HO-1 upregulation. Furthermore, our data showed that the activation of p38 MAPK and Nrf2 translocation are involved in the HO-1 upregulation induced by DMSO. This study reports for the first time that the cytoprotective effect of DMSO in cardiomyocytes is partially mediated by HO-1, which may further explain the mechanisms by which DMSO exerts cardioprotection on H2 O2 injury. J. Cell. Biochem. 115: 1159-1165, 2014. © 2013 Wiley Periodicals, Inc.

  7. [Permeability of isolated rat hepatocyte plasma membranes for molecules of dimethyl sulfoxide].

    PubMed

    Kuleshova, L G; Gordienko, E A; Kovalenko, I F

    2014-01-01

    We have studied permeability of isolated rat hepatocyte membranes for molecules of dimethyl sulfoxide (DMSO) at different hypertonicity of a cryoprotective medium. The permeability coefficient of hepatocyte membranes κ1 for DMSO molecules was shown to be the differential function of osmotic pressure between a cell and an extracellular medium. Ten-fold augmentation of DMSO concentration in the cryoprotective medium causes the decrease of permeability coefficients κ1 probably associated with the increased viscosity in membrane-adjacent liquid layers as well as partial limitations appeared as a result of change in cell membrane shape after hepatocyte dehydration. We have found out that in aqueous solutions of NaCl (2246 mOsm/l) and DMSO (2250 mOsm/l) the filtration coefficient L(p) in the presence of a penetrating cryoprotectant (L(pDMSO) = (4.45 ± 0.04) x 10(-14) m3/Ns) is 3 orders lower compared to the case with electrolyte (L(pNaCl) = (2.25 ± 0.25) x 10(-11) m3/Ns). This phenomenon is stipulated by the cross impact of flows of a cryoprotectant and water at the stage of cell dehydration. Pronounced lipophilicity of DMSO, geometric parameters of its molecule as well as the presence of large aqueous pores in rat hepatocyte membranes allow of suggesting the availability of two ways of penetrating this cryoprotectant into the cells by non-specific diffusion through membrane lipid areas and hydrophilic channels.

  8. Protective effects of dimethyl sulfoxide on labile protein interactions during electrospray ionization.

    PubMed

    Landreh, Michael; Alvelius, Gunvor; Johansson, Jan; Jörnvall, Hans

    2014-05-06

    Electrospray ionization mass spectrometry is a valuable tool to probe noncovalent interactions. However, the integrity of the interactions in the gas-phase is heavily influenced by the ionization process. Investigating oligomerization and ligand binding of transthyretin (TTR) and the chaperone domain from prosurfactant protein C, we found that dimethyl sulfoxide (DMSO) can improve the stability of the noncovalent interactions during the electrospray process, both regarding ligand binding and the protein quaternary structure. Low amounts of DMSO can reduce in-source dissociation of native protein oligomers and their interactions with hydrophobic ligands, even under destabilizing conditions. We interpret the effects of DMSO as being derived from its enrichment in the electrospray droplets during evaporation. Protection of labile interactions can arise from the decrease in ion charges to reduce the contributions from Coulomb repulsions, as well as from the cooling effect of adduct dissociation. The protective effects of DMSO on labile protein interactions are an important property given its widespread use in protein analysis by electrospray ionization mass spectrometry (ESI-MS).

  9. The Effect of Dimethyl Sulfoxide on Supercoiled DNA Relaxation Catalyzed by Type I Topoisomerases.

    PubMed

    Lv, Bei; Dai, Yunjia; Liu, Ju; Zhuge, Qiang; Li, Dawei

    2015-01-01

    The effects of dimethyl sulfoxide (DMSO) on supercoiled plasmid DNA relaxation catalyzed by two typical type I topoisomerases were investigated in our studies. It is shown that DMSO in a low concentration (less than 20%, v/v) can induce a dose-related enhancement of the relaxation efficiency of Escherichia coli topoisomerase I (type IA). Conversely, obvious inhibitory effect on the activity of calf thymus topoisomerase I (type IB) was observed when the same concentration of DMSO is used. In addition, our studies demonstrate that 20% DMSO has an ability to reduce the inhibitory effect on EcTopo I, which was induced by double-stranded oligodeoxyribonucleotides while the same effect cannot be found in the case of CtTopo I. Moreover, our AFM examinations suggested that DMSO can change the conformation of negatively supercoiled plasmid by creating some locally loose regions in DNA molecules. Combining all the lines of evidence, we proposed that DMSO enhanced EcTopo I relaxation activity by (1) increasing the single-stranded DNA regions for the activities of EcTopo I in the early and middle stages of the reaction and (2) preventing the formation of double-stranded DNA-enzyme complex in the later stage, which can elevate the effective concentration of the topoisomerase in the reaction solution.

  10. Dimethyl sulfoxide (DMSO) attenuates the inflammatory response in the in vitro intestinal Caco-2 cell model.

    PubMed

    Hollebeeck, Sylvie; Raas, Thomas; Piront, Neil; Schneider, Yves-Jacques; Toussaint, Olivier; Larondelle, Yvan; During, Alexandrine

    2011-10-30

    This study aimed to investigate dose effects of dimethyl sulfoxide (DMSO) (0.05-1%) on the intestinal inflammatory response in confluent- and differentiated-Caco-2 cells stimulated with interleukin (IL)-1β or a pro-inflammatory cocktail for 24 h. Cyclooxygenase-2 (COX-2) activity was assayed by incubating inflamed cells with arachidonic acid and then measuring prostaglandin-E(2) (PGE(2)) produced. Soluble mediators (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and COX-2-derived PGE(2)) were quantified by enzyme immunoassays and mRNA expression of 33 proteins by high throughput TaqMan Low Density Array. Data showed that DMSO decreased induced IL-6 and MCP-1 secretions in a dose-dependent manner (P<0.05), but not IL-8; these effects were cell development- and stimulus- independent. Moreover, in IL-1β-stimulated confluent-cells, DMSO dose-dependently reduced COX-2-derived PGE(2) (P<0.05). DMSO at 0.5% decreased significantly mRNA levels of 14 proteins involved in the inflammatory response (including IL-6, IL-1α, IL-1β, and COX-2). Thus, DMSO at low concentrations (0.1-0.5%) exhibits anti-inflammatory properties in the in vitro intestinal Caco-2 cell model. This point is important to be taken into account when assessing anti-inflammatory properties of bioactive compounds requiring DMSO as vehicle, such as phenolic compounds, in order to avoid miss-interpretation of the results.

  11. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.

    PubMed

    Choi, S; Sainz, B; Corcoran, P; Uprichard, S; Jeong, H

    2009-03-01

    The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model.

  12. Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

    PubMed

    Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

    2015-07-01

    The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy.

  13. Multinuclear NMR spectroscopy for differentiation of molecular configurations and solvent properties between acetone and dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Wen, Yuan-Chun; Kuo, Hsiao-Ching; Jia, Hsi-Wei

    2016-04-01

    The differences in molecular configuration and solvent properties between acetone and dimethyl sulfoxide (DMSO) were investigated using the developed technique of 1H, 13C, 17O, and 1H self-diffusion liquid state nuclear magnetic resonance (NMR) spectroscopy. Acetone and DMSO samples in the forms of pure solution, ionic salt-added solution were used to deduce their active sites, relative dipole moments, dielectric constants, and charge separations. The NMR results suggest that acetone is a trigonal planar molecule with a polarized carbonyl double bond, whereas DMSO is a trigonal pyramidal-like molecule with a highly polarized S-O single bond. Both molecules use their oxygen atoms as the active sites to interact other molecules. These different molecular models explain the differences their physical and chemical properties between the two molecules and explain why DMSO is classified as an aprotic but highly dipolar solvent. The results are also in agreement with data obtained using X-ray diffraction, neutron diffraction, and theoretical calculations.

  14. Heterogeneity in binary mixtures of dimethyl sulfoxide and glycerol: fluorescence correlation spectroscopy.

    PubMed

    Chattoraj, Shyamtanu; Chowdhury, Rajdeep; Ghosh, Shirsendu; Bhattacharyya, Kankan

    2013-06-07

    Diffusion of four coumarin dyes in a binary mixture of dimethyl sulfoxide (DMSO) and glycerol is studied using fluorescence correlation spectroscopy (FCS). The coumarin dyes are C151, C152, C480, and C481. In pure DMSO, all the four dyes exhibit a very narrow (almost uni-modal) distribution of diffusion coefficient (Dt). In contrast, in the binary mixtures all of them display a bimodal distribution of Dt with broadly two components. One of the components of D(t) corresponds to the bulk viscosity. The other one is similar to that in pure DMSO. This clearly indicates the presence of two distinctly different nano-domains inside the binary mixture. In the first, the micro-environment of the solute consists of both DMSO and glycerol approximately at the bulk composition. The other corresponds to a situation where the first layer of the solute consists of DMSO only. The burst integrated fluorescence lifetime (BIFL) analysis also indicates presence of two micro-environments one of which resembles DMSO. The relative contribution of the DMSO-like environment obtained from the BIFL analysis is much larger than that obtained from FCS measurements. It is proposed that BIFL corresponds to an instantaneous environment in a small region (a few nm) around the probe. FCS, on the contrary, describes the long time trajectory of the probes in a region of dimension ~200 nm. The results are explained in terms of the theory of binary mixtures and recent simulations of binary mixtures containing DMSO.

  15. Solvation structure and transport properties of alkali cations in dimethyl sulfoxide under exogenous static electric fields

    SciTech Connect

    Kerisit, Sebastien; Vijayakumar, M. E-mail: karl.mueller@pnnl.gov; Han, Kee Sung; Mueller, Karl T. E-mail: karl.mueller@pnnl.gov

    2015-06-14

    A combination of molecular dynamics simulations and pulsed field gradient nuclear magnetic resonance spectroscopy is used to investigate the role of exogenous electric fields on the solvation structure and dynamics of alkali ions in dimethyl sulfoxide (DMSO) and as a function of temperature. Good agreement was obtained, for select alkali ions in the absence of an electric field, between calculated and experimentally determined diffusion coefficients normalized to that of pure DMSO. Our results indicate that temperatures of up to 400 K and external electric fields of up to 1 V nm{sup −1} have minimal effects on the solvation structure of the smaller alkali cations (Li{sup +} and Na{sup +}) due to their relatively strong ion-solvent interactions, whereas the solvation structures of the larger alkali cations (K{sup +}, Rb{sup +}, and Cs{sup +}) are significantly affected. In addition, although the DMSO exchange dynamics in the first solvation shell differ markedly for the two groups, the drift velocities and mobilities are not significantly affected by the nature of the alkali ion. Overall, although exogenous electric fields induce a drift displacement, their presence does not significantly affect the random diffusive displacement of the alkali ions in DMSO. System temperature is found to have generally a stronger influence on dynamical properties, such as the DMSO exchange dynamics and the ion mobilities, than the presence of electric fields.

  16. Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex

    PubMed Central

    Soltani, Narjes; Mohammadi, Elham; Allahtavakoli, Mohammad; Shamsizadeh, Ali; Roohbakhsh, Ali; Haghparast, Abbas

    2016-01-01

    Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID:27563414

  17. Amphipathic polymer-mediated uptake of trehalose for dimethyl sulfoxide-free human cell cryopreservation.

    PubMed

    Sharp, Duncan M C; Picken, Andrew; Morris, Timothy J; Hewitt, Christopher J; Coopman, Karen; Slater, Nigel K H

    2013-12-01

    For stem cell therapy to become a routine reality, one of the major challenges to overcome is their storage and transportation. Currently this is achieved by cryopreserving cells utilising the cryoprotectant dimethyl sulfoxide (Me2SO). Me2SO is toxic to cells, leads to loss of cell functionality, and can produce severe side effects in patients. Potentially, cells could be frozen using the cryoprotectant trehalose if it could be delivered into the cells at a sufficient concentration. The novel amphipathic membrane permeabilising agent PP-50 has previously been shown to enhance trehalose uptake by erythrocytes, resulting in increased cryosurvival. Here, this work was extended to the nucleated human cell line SAOS-2. Using the optimum PP-50 concentration and media osmolarity, cell viability post-thaw was 60 ± 2%. In addition, the number of metabolically active cells 24h post-thaw, normalised to that before freezing, was found to be between 103 ± 4% and 91 ± 5%. This was found to be comparable to cells frozen using Me2SO. Although reduced (by 22 ± 2%, p=0.09), the doubling time was found not to be statistically different to the non-frozen control. This was in contrast to cells frozen using Me2SO, where the doubling time was significantly reduced (by 41 ± 4%, p=0.004). PP-50 mediated trehalose delivery into cells could represent an alternative cryopreservation protocol, suitable for research and therapeutic applications.

  18. Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

    PubMed Central

    García, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María C.

    2014-01-01

    Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole. PMID:25406084

  19. Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya.

    PubMed

    Njenga, S M; Wamae, C N; Njomo, D W; Mwandawiro, C S; Molyneux, D H

    2008-10-01

    Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

  20. Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms.

    PubMed

    Hermann, Robert; Mungo, Julius; Cnota, Peter Jürgen; Ziegler, Dan

    2014-01-01

    The present study aimed to examine the enantiomer-selective pharmacokinetics (PK), relative bioavailability (Frel), and sex effects of various oral dosage forms of racemic alpha-lipoic acid (ALA). In an open-label, randomized, four-period, four-sequence crossover study, 24 healthy adult subjects (12 males and 12 females) received single doses of 600 mg of ALA in fasted state at four different occasions as follows: three 200 mg tablets (T 200); two 300 mg tablets (T 300); one 600 mg tablet (T 600); and a racemic ALA solution (OS). All tablet formulations (Thioctacid HR) were considered test treatments, while the OS (Thioctacid, 600 T) served as the reference treatment. Serial blood samples were collected over 8 hours postdose to quantify R-(+)- and S-(-)-ALA enantiomer plasma concentrations for the PK evaluation. The maximum observed plasma concentration (Cmax) and total exposure (area under the curve [AUC]0-t) were compared between treatments by analysis of variance. Weight-normalized Cmax and the AUC data of male and female study subjects were applied to examine the presence of sex effects. All treatments displayed rapid absorption of both enantiomers with median time to maximum concentration (tmax) values ranging from 0.33-0.5 hours. The Frel of all tablet formulations was comparable, with R-(+)-enantiomer Cmax test/reference ratios ranging from 36% (T 600) to 43% (T 200), and R-(+)-enantiomer AUC test/reference ratios ranging from 64% (T 600) to 79% (T 300), indicating a favorable Frel of all tablet formulations, especially in terms of the total extent of absorption (AUC). An examination of weight-normalized female/male Cmax and AUC sex ratios for both ALA enantiomers indicated the absence of a significant sex effect for Cmax, as well as 20%-26% and 25%-32% higher R-(+)- and S-(-)-ALA enantiomer AUC outcomes in females when compared to males. The observed modest sex effect was comparable for both ALA enantiomers and across all formulations, and it did not appear