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Sample records for alfa darifenacin hydrobromide

  1. Darifenacin

    MedlinePlus

    ... overactive bladder (a condition in which the bladder muscles contract uncontrollably and cause frequent urination, urgent need ... called antimuscarinics. It works by relaxing the bladder muscles to prevent urgent, frequent, or uncontrolled urination.

  2. Pharmacokinetics and metabolism of darifenacin in the mouse, rat, dog and man.

    PubMed

    Beaumont, K C; Cussans, N J; Nichols, D J; Smith, D A

    1998-01-01

    1. Following intravenous administration to animals at 2.5 mg/kg, darifenacin exhibited terminal plasma half-lifes < 2 h due to high plasma clearance (with respect to blood flow) and volumes of distribution greater than total body water. 2. Following oral administration to animals at doses > 4 mg/kg there was evidence of saturation of clearance since oral AUCs exceeded those expected from the high plasma clearances. In addition, terminal plasma half-lifes were greater than those estimated from intravenous administration. 3. In man, oral clearance was high with respect to liver blood flow. 4. Following oral administration of the radiolabelled drug to animals and man, unchanged darifenacin was only a minor component of the faecal radioactivity indicating that darifenacin was well absorbed from the gut. 5. Darifenacin was metabolized by three main routes in all species: monohydroxylation, oxidative dihydrobenzfuran ring opening and N-dealkylation. There were no marked species differences in the metabolism of darifenacin.

  3. 21 CFR 556.308 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... halofuginone hydrobromide and the target tissue selected is liver. A tolerance is established in broilers of 0... liver. These marker residue concentrations in liver correspond to total residue concentrations of 0.3 part per million in liver. The safe concentrations for total residues of halofuginone hydrobromide...

  4. 21 CFR 556.308 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... halofuginone hydrobromide and the target tissue selected is liver. A tolerance is established in broilers of 0... liver. These marker residue concentrations in liver correspond to total residue concentrations of 0.3 part per million in liver. The safe concentrations for total residues of halofuginone hydrobromide...

  5. 21 CFR 556.308 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... halofuginone hydrobromide and the target tissue selected is liver. A tolerance is established in broilers of 0... liver. These marker residue concentrations in liver correspond to total residue concentrations of 0.3 part per million in liver. The safe concentrations for total residues of halofuginone hydrobromide...

  6. 21 CFR 556.308 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... halofuginone hydrobromide and the target tissue selected is liver. A tolerance is established in broilers of 0... liver. These marker residue concentrations in liver correspond to total residue concentrations of 0.3 part per million in liver. The safe concentrations for total residues of halofuginone hydrobromide...

  7. 21 CFR 556.308 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... to monitor for total residues of halofuginone hydrobromide in broilers and turkeys is parent....16 part per million and in turkeys of 0.13 part per million for parent halofuginone hydrobromide in... the uncooked edible tissues of broilers and turkeys are 0.1 part per million in muscle, 0.3 part...

  8. Dornase Alfa

    MedlinePlus

    ... and to improve lung function in patients with cystic fibrosis. It breaks down the thick secretions in the ... your doctor.Dornase alfa is used to treat cystic fibrosis but does not cure it. Continue to use ...

  9. Pharmacokinetics and metabolism of darifenacin in the mouse, rat, dog and man.

    PubMed

    Beaumont, K C; Cussans, N J; Nichols, D J; Smith, D A

    1998-01-01

    1. Following intravenous administration to animals at 2.5 mg/kg, darifenacin exhibited terminal plasma half-lifes < 2 h due to high plasma clearance (with respect to blood flow) and volumes of distribution greater than total body water. 2. Following oral administration to animals at doses > 4 mg/kg there was evidence of saturation of clearance since oral AUCs exceeded those expected from the high plasma clearances. In addition, terminal plasma half-lifes were greater than those estimated from intravenous administration. 3. In man, oral clearance was high with respect to liver blood flow. 4. Following oral administration of the radiolabelled drug to animals and man, unchanged darifenacin was only a minor component of the faecal radioactivity indicating that darifenacin was well absorbed from the gut. 5. Darifenacin was metabolized by three main routes in all species: monohydroxylation, oxidative dihydrobenzfuran ring opening and N-dealkylation. There were no marked species differences in the metabolism of darifenacin. PMID:9493320

  10. 21 CFR 558.265 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... articles containing 6 grams of halofuginone hydrobromide per kilogram. (b) Approvals. See No. 016592 in... use. (1) It is used in feed for broiler chickens as follows: (i) Amount. 2.72 grams per ton. (A... lakes, ponds, or streams. (ii) Amount per ton. Halofuginone 2.72 grams (0.0003 percent)...

  11. 21 CFR 558.265 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... articles containing 6 grams of halofuginone hydrobromide per kilogram. (b) Approvals. See No. 016592 in... use. (1) It is used in feed for broiler chickens as follows: (i) Amount. 2.72 grams per ton. (A... lakes, ponds, or streams. (ii) Amount per ton. Halofuginone 2.72 grams (0.0003 percent)...

  12. A Prospective, Comparative Study of the Occurrence and Severity of Constipation with Darifenacin and Trospium in Overactive Bladder

    PubMed Central

    Pundarikaksha, Hulikallu Purushotama; Hanumantharaju, Basavanahalli Krishnaiah; Anusha, Satenahalli Javaregowda

    2015-01-01

    Introduction: Darifenacin and trospium are the commonly used antimuscarinics in the management of overactive bladder (OAB). Constipation is the second most common treatment related side-effect. Though its incidence with the above two medications is known, data on their comparative severity and impact on patient’s well-being is lacking. Materials and Methods: Sixty subjects with OAB included in the study were randomized in 1:1 fashion to receive either darifenacin 7.5 mg OD or trospium extended release 60 mg OD. Treatment response was monitored using overactive bladder symptom score (OABSS). The severity of constipation was assessed using McMillan & Williams Constipation assessment scale (CAS), Bristol stool form scale and Knowles-Eccersley-Scott-Symptom (KESS) questionnaire score administered at baseline, 2 and 4 weeks of treatment. Results: OABSS improved significantly, -5.80 ± 3.99 (p = 0.0005) and -5.27 ± 2.98 (p = 0.0005) in darifenacin and trospium groups respectively. However, the difference between the two groups was not significant either at 2 weeks (p = 0.952) or 4 weeks (p = 0.654) of treatment. A significant decrease in stool consistency was noted with darifenacin treatment (p < 0.05), but the same was not seen with trospium (p = 0.076). There was no significant difference in scores of KESS questionnaire between baseline, 2 weeks and 4 weeks, both within the group and between the groups (p > 0.05). McMillan & Williams CAS scores increased at week 2 and week 4, in comparison with baseline scores in both darifenacin and trospium treated patients, however, the difference between the two groups was not statistically significant (p > 0.05). Conclusion: Darifenacin and trospium are equally efficacious and comparable in tolerability in terms of constipation severity and its impact on patient well-being. PMID:25954630

  13. Darbepoetin Alfa Injection

    MedlinePlus

    ... treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure ( ... alfa cannot be used in place of a red blood cell transfusion to treat severe anemia and ...

  14. Treatment of overactive bladder in the aging population: focus on darifenacin.

    PubMed

    Jha, Swati; Parsons, Matthew

    2006-01-01

    Anticholinergics are commonly used in primary and secondary care settings for the treatment of overactive bladder syndrome. The number of anticholinergic drugs available on the market is increasing and various studies, both observational and randomized controlled trials, have evaluated effectiveness of the different preparations available. When anticholinergic therapy is prescribed, there is still uncertainty about which anticholinergic drugs are most effective, at which dose, and by which route of administration. There is also uncertainty about the role of anticholinergic drugs in different patient groups, particularly in the elderly. The rationale for using anticholinergic drugs in the treatment of overactive bladder syndrome is to block the parasympathetic acetylcholine pathway and thus abolish or reduce the intensity of detrusor muscle contraction. There are currently five recognized subtypes of muscarinic receptor; the M1, M2, and M3 subtypes are of interest in bladder activity. Muscarinic receptors are found in other parts of the body, eg, in the gut, salivary glands, tear ducts. Side effects associated with non-selective antimuscarinics can be particularly distressing in the elderly. The development of bladder selective M3 specific antagonists has the advantage of providing increased efficacy with minimal side effects. Darifenacin is one such preparation. The aim of this review is to assess the pharmacology, interactions and the safety and tolerability of darifenacin in the treatment of overactive bladder in the elderly population with particular reference to clinical trial data available.

  15. Peginterferon Alfa-2a Injection

    MedlinePlus

    ... alfa-2a is also used to treat chronic hepatitis B infection (swelling of the liver caused by a ... the amount of hepatitis C virus (HCV) or hepatitis B virus (HBV) in the body. Peginterferon alfa-2a ...

  16. ALFA: Automated load forecasting assistant

    SciTech Connect

    Jabbour, K.; Riveros, J.F.V.; Landsbergen, D.; Meyer, W.

    1988-08-01

    ALFA, an expert system for forecasting short term demand for electricity is presented. ALFA is in operation at the new Energy Management System center at Niagara Mohawk Power Corporation in Upstate New York, generating the real time hourly load forecasts up to 48 hours in advance. ALFA uses an extensive 10 year historical data base of hourly observations of 12 weather variables and load, and a rule base that takes into account daily, weekly, and seasonal variations of load, as well as holidays, special events, and load growth. A satellite interface for the real-time acquisition of weather data, and the machine-operator interface are also discussed.

  17. Dextromethorphan hydrobromide preparations on the Belgian market--a comparative study.

    PubMed

    Fierens, C; Corthout, J

    2009-03-01

    Liquid preparations for oral use containing dextromethorphan hydrobromide were verified on identity, content and microbiological quality. The assay method was previously validated according to international guidelines. All examined products complied with the postulated requirements.

  18. Mercaptoimidazolylpropionic acid hydrobromide. Inhibition of tadpole collagenase and related properties.

    PubMed

    Yankeelov, J A; Parish, H A; Spatola, A F

    1978-07-01

    A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations. PMID:209189

  19. Unusual aggregation of bis(2-quinuclidinium-butyrate) hydrobromides

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Katrusiak, A.; Szafran, M.

    2010-12-01

    The molecular structure of di-[bis(2-quinuclidinium-butyrate) hydrobromide], [(QNBu) 2HBr] 2 ( 1), has been characterized by single-crystal X-ray diffraction, infrared spectroscopy and DFT calculations. The crystals ( 1) are monoclinic, space group P2 1/c with [(QNBu) 2HBr] 2 symmetry-independent units. The complex 1 consists of two independent homoconjugated cations, in which two ( S) QNBu semications, and ( S) and ( R) QNBu semications are joined by short, symmetrical O⋯H⋯O hydrogen bonds of 2.418(12) and 2.411(13) Å, respectively. The bromide anions interact electrostatically with the one positively charged nitrogen atom of each cation. The presence of short OHO hydrogen bonds is confirmed by the broad absorption in the 1500-400 cm -1 region, with the center of gravity, νH, at ca. 900 cm -1, in the solid-state FTIR spectrum. In the structure of [(QNBu) 2HBr] 2 ( 2) optimized at the B3LYP/6-31G(d,p) level of theory, the 2-quinuclidinium-butyrate units are non-equivalent. In each homoconjugated cation the 2-quinuclidinium-butyric acid interacts with the QNBu inner salt by the short, asymmetric O-H···O hydrogen bonds of 2.440 and 2.446 Å, respectively. Each bromide anion interacts electrostatically with the positively charged nitrogen atoms from both homoconjugated cations, which fold into a globular supramolecular aggregate.

  20. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    PubMed

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability. PMID:27091045

  1. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    PubMed

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.

  2. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... powder at room temperature and away from excess heat and moisture (not in the bathroom).It is best to inject peginterferon alfa-2b solution in vials or injection pens immediately after mixing. If necessary, vials or injection pens containing prepared peginterferon alfa-2b solution may be stored ...

  3. ALFA: Automated Line Fitting Algorithm

    NASA Astrophysics Data System (ADS)

    Wesson, R.

    2015-12-01

    ALFA fits emission line spectra of arbitrary wavelength coverage and resolution, fully automatically. It uses a catalog of lines which may be present to construct synthetic spectra, the parameters of which are then optimized by means of a genetic algorithm. Uncertainties are estimated using the noise structure of the residuals. An emission line spectrum containing several hundred lines can be fitted in a few seconds using a single processor of a typical contemporary desktop or laptop PC. Data cubes in FITS format can be analysed using multiple processors, and an analysis of tens of thousands of deep spectra obtained with instruments such as MUSE will take a few hours.

  4. Epoetin alfa: into the new millennium.

    PubMed

    Adamson, J W

    1998-06-01

    First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.

  5. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... is also available as a different product (PEG-Intron) that is used to treat chronic hepatitis C ( ... to remove it. If you are using Peg-Intron, read the monograph entitled Peginterferon alfa-2b (PEG- ...

  6. Scientific Organization of the ALFA Legacy Surveys

    NASA Astrophysics Data System (ADS)

    Brown, R. L.

    2005-12-01

    The ALFA Legacy Surveys are organized as a partnership between NAIC and the community of interested and involved academic researchers. NAIC has committed a large fraction of the time on the Arecibo telescope to the ALFA surveys for the next 5 or more years in return for which the ALFA Consortia are making a large commitment of personnel resources in conducting the surveys, writing the needed software, and archiving the data for use by others. The surveys are facilitated by means of commensal observations--simultaneous observations made by two or more Consortia each processing the same received signal using different spectrometers designed for different scientific applications. The spectrometer specifications are set by the Consortia, and the hardware is built by NAIC under contract to university-based instrumentation groups. The NAIC vision of its partnership with the ALFA consortia: (1) Is necessary to the success of the ALFA legacy surveys; (2) Provides the opportunity to re-establish an effective partnership between the national observatory and the academic research community; (3) Reflects the maturity of 50 years of research in radio astronomy. NAIC is operated by Cornell University under cooperative agreement with the NSF.

  7. Efmoroctocog Alfa: A Review in Haemophilia A.

    PubMed

    Frampton, James E

    2016-09-01

    Efmoroctocog alfa (Elocta(®), Eloctate(®), Eloctate™), a first-in-class recombinant factor VIII-Fc fusion protein (rFVIIIFc), has an extended half-life compared with conventional factor VIII (FVIII) preparations, including recombinant FVIII (rFVIII) products. It is approved for the treatment and prophylaxis of bleeding in patients with haemophilia A in multiple countries worldwide. Data accumulated from pivotal phase III studies (A-LONG in adults and adolescents aged ≥12 years; Kids A-LONG in children aged <12 years) and their ongoing extension study (ASPIRE) have demonstrated the long-term effectiveness of efmoroctocog alfa for the treatment of acute bleeding episodes, perioperative management and routine prophylaxis in previously treated males with severe haemophilia A. Among patients on individualized efmoroctocog alfa prophylaxis who had previously received FVIII prophylaxis, all but one of those aged ≥12 years and three-quarters of those aged <12 years reduced their injection frequency compared with their pre-study regimen. FVIII replacement therapy with efmoroctocog alfa was generally well tolerated in previously treated patients, with no evidence of increased immunogenicity. The safety and efficacy of FVIII replacement therapy with efmoroctocog alfa in previously untreated males aged <6 years with severe haemophilia A are currently being evaluated. Although there are no direct, head-to-head studies, the available clinical trial evidence indicates that efmoroctocog alfa provides an effective alternative to conventional FVIII preparations (including rFVIIIs) for the management of haemophilia A. Moreover, by reducing the frequency of injections required, it has the potential to reduce treatment burden, and hence improve adherence to prophylaxis. PMID:27487799

  8. ALFA: an automated line fitting algorithm

    NASA Astrophysics Data System (ADS)

    Wesson, R.

    2016-03-01

    I present the automated line fitting algorithm, ALFA, a new code which can fit emission line spectra of arbitrary wavelength coverage and resolution, fully automatically. In contrast to traditional emission line fitting methods which require the identification of spectral features suspected to be emission lines, ALFA instead uses a list of lines which are expected to be present to construct a synthetic spectrum. The parameters used to construct the synthetic spectrum are optimized by means of a genetic algorithm. Uncertainties are estimated using the noise structure of the residuals. An emission line spectrum containing several hundred lines can be fitted in a few seconds using a single processor of a typical contemporary desktop or laptop PC. I show that the results are in excellent agreement with those measured manually for a number of spectra. Where discrepancies exist, the manually measured fluxes are found to be less accurate than those returned by ALFA. Together with the code NEAT, ALFA provides a powerful way to rapidly extract physical information from observations, an increasingly vital function in the era of highly multiplexed spectroscopy. The two codes can deliver a reliable and comprehensive analysis of very large data sets in a few hours with little or no user interaction.

  9. Asfotase alfa therapy for children with hypophosphatasia

    PubMed Central

    Madson, Katherine L.; Phillips, Dawn; Reeves, Amy L.; McAlister, William H.; Yakimoski, Amy; Mack, Karen E.; Hamilton, Kim; Kagan, Kori; Fujita, Kenji P.; Thompson, David D.; Moseley, Scott; Odrljin, Tatjana; Rockman-Greenberg, Cheryl

    2016-01-01

    Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6–12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti–asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show

  10. Asfotase alfa therapy for children with hypophosphatasia

    PubMed Central

    Madson, Katherine L.; Phillips, Dawn; Reeves, Amy L.; McAlister, William H.; Yakimoski, Amy; Mack, Karen E.; Hamilton, Kim; Kagan, Kori; Fujita, Kenji P.; Thompson, David D.; Moseley, Scott; Odrljin, Tatjana; Rockman-Greenberg, Cheryl

    2016-01-01

    Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6–12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti–asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show

  11. Introduction to ALFA and the GALFA Consortium

    NASA Astrophysics Data System (ADS)

    Goldsmith, P. F.

    2004-12-01

    In this talk, I give an overview of the ALFA instrument, a 7 element focal plane array on the Arecibo 305m telescope, which covers the frequency range 1225 to 1525 MHz. Each pixel observes two orthogonal linear polarizations. There are several spectrometers for different types of observations. For Galactic astronomy, a FFT spectrometer has been developed by D. Werthimer and colleagues, which has 8192 channels covering 7 MHz ( 1500 km/s at 0.2 km/s resolution) along with 256 channels covering 100 MHz intended for measuring and removing spectral baselines. ALFA test observations have been underway since August 2004, and astronomical observations should be ramping up through Fall 2004 and be in full swing by early 2005. The GALFA consortium is comprised of individuals interested in using the ALFA system for galactic astronomy. It is divided by interest into subconsortia, focusing on a number of the outstanding problems which can be addressed by ALFA on the Arecibo telescope, with 8-10 K/Jy gain, 3.5' beamwidth, and 30-35 K system temperature. One subconsortium is planning to carry out a survey of 21cm continuum radiation from the Milky Way, focusing on mapping the polarized emission in order to perform Faraday tomography of the magnetic field distribution. Radio recombination lines are the focus of another subconsortium; the ALFA system will be able to observe multiple RRLs that fall within its bandpass. HI emission and absorption will be utilized by a number of consortia, but applied to different problems, including the Galactic plane, high latitude clouds, high velocity clouds, turbulence, and the relationship of the atomic and molecular components of the ISM. Each subconsortium is making plans, starting with relatively small-scale projects, and working towards large-scale projects. Commensal (GALFA together with extragalactic or pulsar observations) are anticipated, using multiple signal processing systems simultaneously.

  12. Arecibo Pulsar and Transient Surveys Using ALFA

    NASA Astrophysics Data System (ADS)

    Cordes, J. M.

    2008-02-01

    A large scale survey for pulsars and transients is being conducted at the Arecibo Observatory using the Arecibo L-band Feed Array (ALFA). Data acquisition so far has been with correlation spectrometers that analyze a 0.1 GHz bandwidth at 1.4 GHz. The 256 frequency channels limit dispersion smearing to 1.2 ms at DMmax = 103 pc cm-3 while the sampling interval of 64 μs equals the dispersion smearing at DM~54 pc cm-3, providing high sensitivity to millisecond pulsars with standard periods out to implied distances of several kpc at low Galactic latitudes. In early 2008, we will use a new set of polyphase filter bank systems that provide the same time and frequency resolutions but over ALFA's full 0.3 GHz bandwidth. Currently the survey covers sky positions within 5° of the Galactic plane that are reachable with Arecibo. Preliminary results are given for some of the discoveries made so far, which include millisecond pulsars, a relativistic binary pulsar, a likely counterpart of a Compton GRO/EGRET gamma-ray source, and transient pulsars (including `RRATs''). We discuss the methodology of the survey, which includes archival of raw survey data at the Cornell Center for Advanced Computing and processing at distributed sites. The survey and follow up observations, which include timing observations, multiwavelength searches for orbital companions in the case of binary pulsars, etc. are organized through the Pulsar-ALFA (PALFA) Consortium. We expect the Galactic plane survey to continue until at least 2010, most likely involving multiple passes on each sky position to optimize detection of variable sources. The ALFA system will also be used to survey intermediate Galactic latitudes for millisecond pulsars, relativistic binaries with large systemic velocities, and runaway pulsars that will escape the Galaxy.

  13. Simultaneous high-pressure liquid chromatographic determination of acetaminophen, guaifenesin, and dextromethorphan hydrobromide in cough syrup.

    PubMed

    McSharry, W O; Savage, I V

    1980-02-01

    Acetaminophen (I), guaifenesin (II), and dextromethorphan hydrobromide (III) were separated and quantitated simultaneously in cough syrup by high-pressure liquid chromatography. A chemically bonded octadecylsilane stationary phase was used with a mobile phase of 48% (v/v) aqueous methanol. The mobile phase pH was stabilized to 4.2 by adding formic acid--ammonium formate buffer (approximately 0.4%). The internal standard was o-dinitrobenzene. Retention volumes were 4 ml for I, 6 ml for II, 11 ml for the internal standard, and 20 ml for III. Inactive syrup components did not interfere, permitting direct diluted sample injection. Results on active ingredients were essentially 100% of the claim, with standard deviations of +/- 1.5, 1.2, and 2.1% for I, II, and III, respectively. PMID:7359328

  14. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; Romeo, V. D.; Behl, C. R.

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  15. Synthesis, growth and characterization of nonlinear optical crystal: L-tyrosine hydrobromide

    NASA Astrophysics Data System (ADS)

    Moolya, B. Narayana; Dharmaprakash, S. M.

    2006-05-01

    L-tyrosine hydrobromide ( L-THB) a semi organic nonlinear optical material with molecular formula C 9H 12NO 3Br has been synthesized at ambient temperature. Spectral, thermal and optical techniques have been employed to characterize the new material. The solubility of L-THB at varying temperatures was determined in different concentrations of hydrobromic acid. Bulk single crystals of size 15×7×4 mm 3 of L-THB were grown by slow evaporation method at constant temperature. Powder X-ray diffraction pattern of the grown L-THB has been indexed. Functional groups present in the sample were identified by FTIR spectral analysis. Chemical composition of the synthesized material was confirmed by carrying out CHN analysis. Thermal stability of L-THB was determined from TGA/DTA and DSC response curves. Mechanical hardness of the grown crystal L-THB was determined and Vickers hardness number was calculated. The Kurtz powder second harmonic generation test shows that the compound is a potential candidate for optical second harmonic generation. The optical transparency range and the lower cut-off of UV transmission were identified from the recorded UV-vis spectrum of L-THB. The optical energy gap of L-THB is 3 eV.

  16. Factors affecting the stability and performance of ipratropium bromide; fenoterol hydrobromide pressurized-metered dose inhalers.

    PubMed

    Ninbovorl, Jenjira; Sawatdee, Somchai; Srichana, Teerapol

    2013-12-01

    The aim of the study was to investigate the factors affecting the stability and performance of ipratropium bromide and fenoterol hydrobromide in a pressurized-metered dose inhaler (pMDI). A factorial design was applied to investigate the effects of three parameters (propellant, water, and ethanol) on the performance of 27 designed formulations of a solution-based pMDI. The formulations that contained a hydrofluoroalkane (HFA) propellant lower than 72% v/v and an ethanol concentration higher than 27% v/v remained as clear solutions. Nine formulations that contained the HFA propellant higher than 74% v/v precipitated. The results indicated that it was not only the HFA propellant content of the formulations that was related to the formulation instability but also ethanol content. Only six formulations from the 18 formulations, that did not precipitate, produced drug contents that were within the acceptable range (80-120%). These six formulations generated aerosols with mass median aerodynamic diameters (MMAD) of approximately 2 μm with a fine particle fraction (FPF; particle size, <6.4 μm) between 45% and 52%. The MMAD and FPF did not change significantly after 6 months of storage (P > 0.05). PMID:23975571

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride.

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  19. Structure and spectroscopic properties of bis(1-carboxyethyl-3-aminopyridinium) hydrobromide monohydrate

    NASA Astrophysics Data System (ADS)

    Kowalczyk, I.; Katrusiak, A.; Komasa, A.; Szafran, M.

    2011-05-01

    The structure of bis(1-carboxyethyl-3-aminopyridinium) hydrobromide monohydrate, (3-NH 2PB2) 2HBrṡH 2O ( 1), has been studied by X-ray diffraction, B3LYP/6-311G(d,p) calculations, FTIR and NMR spectroscopy and calorimetric measurements. The compound crystallizes in orthorhombic, space group Pbca. The Br anion and water molecules are positionally disordered so that Br(1) and O(1w) are located at the same positions with the same average occupations and they form O(1w)H⋯Br bonded zigzag chains along [1 0 0], with the Br⋯O(1w)⋯Br and O(1w)⋯Br⋯O(1w) angles equal 121.0(3)°. These chains are connected to the O(1)⋯H(1)⋯O(11) bonded cations through NH⋯Br and NH⋯O(1w) bonds. A pair of 3-NH 2PB2 molecules is bridged by a short symmetric O(1)·H·O(11) hydrogen bond of 2.462(6) Ǻ. The FTIR spectrum of ( 1) shows a broad and intense absorption in the 1500-400 cm -1 range, similar to that in the spectra of type A acid salts of carboxylic acids and other 2:1 betaine complexes with mineral acids. The assignment of the anharmonic experimental solid-state vibrational frequencies of the compound investigated is proposed based on the second-derivative spectrum ( d2). Correlations between the experimental 13C and 1H NMR chemical shifts ( δexp) and the GIAO/B3LYP/6-311G(d,p) calculated magnetic isotropic shielding constants ( σcal) in DMSO-d 6, δexp = a + b· σcalc, are reported.

  20. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer's disease.

    PubMed

    Woo, Fong Yen; Basri, Mahiran; Masoumi, Hamid Reza Fard; Ahmad, Mansor B; Ismail, Maznah

    2015-01-01

    Galantamine hydrobromide (GH) is an effective drug for Alzheimer's disease. It is currently delivered via the oral route, and this might cause nausea, vomiting, and gastrointestinal disturbance. In the present work, GH was formulated in a gel-type drug reservoir and then optimized by using response surface methodology (RSM) based on central composite design. This optimization study involved three independent variables (carbopol amount, triethanolamine amount, and GH amount) and two dependent variables (cumulative drug release amount at 8 hours and the permeation flux of drug). Two models using expert design software were fitted into a quadratic polynomial model. The optimized gel was formulated with 0.89% w/w carbopol, 1.16% w/w triethanolamine, and 4.19% w/w GH. Optimization analysis revealed that the proposed formulation has the predicted cumulative drug release amount at 8 hours of 17.80 mg·cm(-2) and the predicted permeation flux of 2.27 mg·cm(-2)/h. These predicted values have good agreement to actual cumulative drug release amount at 8 hours (16.93±0.08 mg·cm(-2)) and actual permeation flux (2.32±0.02 mg·cm(-2)/h). This optimized reservoir formulation was then fabricated in the transdermal patch system. This patch system has moderate pH, high drug content, and controlled drug-release pattern. Thus, this patch system has the potential to be used as the drug carrier for the treatment of Alzheimer's disease. PMID:26089664

  1. Erythropoietin, the biology of erythropoiesis and epoetin alfa. An overview.

    PubMed

    Bieber, E

    2001-05-01

    Erythropoietin, a glycoprotein hormone, is synthesized predominantly in the kidney and secreted by renal cortical interstitial cells in response to tissue hypoxia. Erythropoietin is the main regulator of the production of red blood cells. It functions in the recruitment and differentiation of erythroid progenitor cells and aids in their maintenance and survival. Erythropoietin also stimulates the synthesis of hemoglobin. In the last 15 years, the ready availability of recombinant human erythropoietin (r-HuEPO, epoetin alfa) has permitted the clinical investigation and application of this hormone to the treatment of anemia in various patient populations. Epoetin alfa has been shown to accelerate erythropoiesis and reduce allogeneic blood transfusion in major elective, noncardiac, nonvascular surgery and in certain anemic patients with chronic renal failure, nonmyeloid malignancies and human immunodeficiency virus infection. In addition to improving hematologic parameters, epoetin alfa therapy can enhance health-related quality of life in these patients. The success of epoetin alfa in treating anemia in other surgical populations suggests that it may be of benefit in treating the perioperative anemia that is highly prevalent in gynecologic surgery patients. Further investigation of the use of epoetin alfa in patients undergoing gynecologic surgery would increase awareness of its benefits for this patient population.

  2. Role of elosulfase alfa in mucopolysaccharidosis IVA.

    PubMed

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration's approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age.

  3. Role of elosulfase alfa in mucopolysaccharidosis IVA.

    PubMed

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration's approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age. PMID:27366102

  4. Role of elosulfase alfa in mucopolysaccharidosis IVA

    PubMed Central

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration’s approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age. PMID:27366102

  5. Laboratory trend analyses and proactive adjustments to minimize the need for holding epoetin alfa doses.

    PubMed

    Breiterman-White, Randee; Reznicek, Jacci

    2008-01-01

    Holding doses of epoetin alfa (Epogen) alters the balance between red blood cell production and death rates, and leads to a decrease in hemoglobin (Hb) levels. Although clinical circumstances sometimes require that epoetin alfa doses be held, this can be minimized by monitoring longitudinal trends, predicting the probable future course of Hb, and intervening to proactively adjust epoetin alfa doses before holding is required.

  6. Velaglucerase alfa in the treatment of Gaucher disease type 1.

    PubMed

    Burrow, Thomas A; Grabowski, Gregory A

    2011-02-01

    Gaucher disease is an autosomal recessively inherited lysosomal storage disease that results from the defective activity of the enzyme acid β-glucosidase (glucocerebrosidase). Velaglucerase alfa was recently developed and approved as an alternative form to imiglucerase enzyme therapy. Despite differences in primary structure and glycosylation patterns, recent preclinical and clinical trials of the preparation have shown similar efficacy and safety profiles to those of imiglucerase. The development of alternative therapies, such as velaglucerase alfa for Gaucher disease, is providing clinicians with a larger armamentarium of therapies, allowing for a more personalized approach to patient care. PMID:21927713

  7. Velaglucerase alfa: a new option for Gaucher disease treatment.

    PubMed

    Zimran, A

    2011-07-01

    Type 1 Gaucher disease (GD) results from inherited β-glucocerebrosidase gene mutations, leading to anemia, thrombocytopenia, splenomegaly, hepatomegaly and skeletal disease. Velaglucerase alfa is a β-glucocerebrosidase produced by gene activation in a human cell line, and indicated for type 1 GD. A phase I/II clinical trial (TKT025; N = 12), its ongoing extension (TKT025EXT) and three phase III trials (total N = 82), showed that velaglucerase alfa is generally well tolerated in adult and pediatric patients. Many disease-related parameters improved significantly in two phase III trials in treatment-naïve patients, and were successfully maintained in imiglucerase-experienced patients in a phase II/III switch study. Ten adults in TKT025EXT sustained improvements through 5 years, including bone mineral density. Comparison with imiglucerase shows that velaglucerase alfa is an effective, generally well-tolerated alternative enzyme replacement therapy. In vitro data suggest velaglucerase alfa may be internalized into cells more efficiently and have a lower rate of seroconversion. However, these results do not necessarily correlate with clinical efficacy. PMID:22013559

  8. ALFA: The new ALICE-FAIR software framework

    NASA Astrophysics Data System (ADS)

    Al-Turany, M.; Buncic, P.; Hristov, P.; Kollegger, T.; Kouzinopoulos, C.; Lebedev, A.; Lindenstruth, V.; Manafov, A.; Richter, M.; Rybalchenko, A.; Vande Vyvre, P.; Winckler, N.

    2015-12-01

    The commonalities between the ALICE and FAIR experiments and their computing requirements led to the development of large parts of a common software framework in an experiment independent way. The FairRoot project has already shown the feasibility of such an approach for the FAIR experiments and extending it beyond FAIR to experiments at other facilities[1, 2]. The ALFA framework is a joint development between ALICE Online- Offline (O2) and FairRoot teams. ALFA is designed as a flexible, elastic system, which balances reliability and ease of development with performance using multi-processing and multithreading. A message- based approach has been adopted; such an approach will support the use of the software on different hardware platforms, including heterogeneous systems. Each process in ALFA assumes limited communication and reliance on other processes. Such a design will add horizontal scaling (multiple processes) to vertical scaling provided by multiple threads to meet computing and throughput demands. ALFA does not dictate any application protocols. Potentially, any content-based processor or any source can change the application protocol. The framework supports different serialization standards for data exchange between different hardware and software languages.

  9. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  10. Alfa-one antitrypsin phenotypes and inhalatory pulmonary pathology.

    PubMed

    Amaral-Marques, R; Avila, R; Geada, H; Cochito, M L; Manso, C; Villar, T G

    1980-01-01

    One hundred and twenty nine workers in the cork industry, 69 rural workers, 66 carpet makers, 58 workers in a granite quarry and 51 workers in a rice husking factory were studied from an epidemiologic point of view. All were submitted to a standard questionnaire planned to detect respiratory disease due to inhalatory causes. They were submitted to a clinical examination, summary ventilatory function tests, a 70 mm microradiograph, and blood was taken to determine alfa-one antitrypsin and its phenotypes and, in the cork industry workers and rice husking workers, the level of IgA, IgG and IgM. The results are presented and an attempt is made to correlate the various parameters among themselves, and namely alfa-one AT phenotypes with the existence of respiratory pathology. Finally the results are discussed.

  11. Utility of eosin Y as a complexing reagent for the determination of citalopram hydrobromide in commercial dosage forms by fluorescence spectrophotometry.

    PubMed

    Azmi, Syed Najmul Hejaz; Al-Fazari, Ahlam; Al-Badaei, Munira; Al-Mahrazi, Ruqiya

    2015-12-01

    An accurate, selective and sensitive spectrofluorimetric method was developed for the determination of citalopram hydrobromide in commercial dosage forms. The method was based on the formation of a fluorescent ion-pair complex between citalopram hydrobromide and eosin Y in the presence of a disodium hydrogen phosphate/citric acid buffer solution of pH 3.4 that was extractable in dichloromethane. The extracted complex showed fluorescence intensity at λem = 554 nm after excitation at 259 nm. The calibration curve was linear over at concentrations of 2.0-26.0 µg/mL. Under optimized experimental conditions, the proposed method was validated as per ICH guidelines. The effect of common excipients used as additives was tested and the tolerance limit calculated. The limit of detection for the proposed method was 0.121 μg/mL. The proposed method was successfully applied to the determination of citalopram hydrobromide in commercial dosage forms. The results were compared with the reference RP-HPLC method.

  12. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    SciTech Connect

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. )

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  13. Impact of epoetin alfa in chemotherapy-associated anemia.

    PubMed

    Jilani, S M; Glaspy, J A

    1998-10-01

    Anemia associated with cancer and cytotoxic chemotherapy contributes adversely to the quality of life (QOL) of these patients. RBC transfusions have been the traditional treatment, but due to the associated risks, they are not routinely used to treat mild and moderate degrees of anemia Therapy with recombinant human erythropoietin ([EPO] epoetin alfa) in these patients has been effective for both prevention and treatment of anemia, and in decreasing transfusion requirements. More importantly, studies have shown that the addition of epoetin alfa therapy to the treatment of patients receiving cancer chemotherapy is associated with a significant increase in energy level, functional status, and overall QOL. Further studies will be required to define the most efficient and cost-effective dose and schedule of epoetin alfa during cancer chemotherapy, so that its benefits will be available to as many patients as possible. The most important studies will be focused on defining the relationship of dose to response, identifying early predictors of response, and determining cost-effectiveness.

  14. Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: comparative analysis of drug utilization, costs, and hematologic response.

    PubMed

    Persson, Ulf; Borg, Sixten; Jansson, Sandra; Ekman, Tor; Franksson, Lars; Friesland, Signe; Larsson, Anna-Maria

    2005-01-01

    A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (approximately US$9800 or approximately 8300) with epoetin alfa and SEK85,285 (approximately US$11,000 or approximately 9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81% and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.

  15. Pharmacologic Evaluation of Antidepressant Activity and Synthesis of 2-Morpholino-5-phenyl-6H-1,3,4-thiadiazine Hydrobromide.

    PubMed

    Sarapultsev, Alexey P; Chupakhin, Oleg N; Sarapultsev, Petr A; Sidorova, Larisa P; Tseitler, Tatiana A

    2016-01-01

    Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide) for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985), and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction. PMID:27213404

  16. Pharmacologic Evaluation of Antidepressant Activity and Synthesis of 2-Morpholino-5-phenyl-6H-1,3,4-thiadiazine Hydrobromide

    PubMed Central

    Sarapultsev, Alexey P.; Chupakhin, Oleg N.; Sarapultsev, Petr A.; Sidorova, Larisa P.; Tseitler, Tatiana A.

    2016-01-01

    Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide) for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985), and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction. PMID:27213404

  17. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    PubMed Central

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

  18. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa

    PubMed Central

    Orimo, Hideo

    2016-01-01

    Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP. PMID:27274262

  19. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa.

    PubMed

    Orimo, Hideo

    2016-01-01

    Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP. PMID:27274262

  20. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase.

    PubMed

    Zimran, Ari; Pastores, Gregory M; Tylki-Szymanska, Anna; Hughes, Derralynn A; Elstein, Deborah; Mardach, Rebecca; Eng, Christine; Smith, Laurie; Heisel-Kurth, Margaret; Charrow, Joel; Harmatz, Paul; Fernhoff, Paul; Rhead, William; Longo, Nicola; Giraldo, Pilar; Ruiz, Juan A; Zahrieh, David; Crombez, Eric; Grabowski, Gregory A

    2013-03-01

    Velaglucerase alfa is a glucocerebrosidase produced by gene activation technology in a human fibroblast cell line (HT-1080), and it is indicated as an enzyme replacement therapy (ERT) for the treatment of Gaucher disease type 1 (GD1). This multicenter, open-label, 12-month study examined the safety and efficacy of velaglucerase alfa in patients with GD1 previously receiving imiglucerase. Eligible patients, ≥2 years old and clinically stable on imiglucerase therapy, were switched to velaglucerase alfa at a dose equal to their prior imiglucerase dose. Infusion durations were 1 hr every other week. Forty patients received velaglucerase alfa (18 male, 22 female; four previously splenectomized; age range 9-71 years). Velaglucerase alfa was generally well tolerated with most adverse events (AEs) of mild or moderate severity. The three most frequently reported AEs were headache (12 of 40 patients), arthralgia (9 of 40 patients), and nasopharyngitis (8 of 40 patients). No patients developed antibodies to velaglucerase alfa. There was one serious AE considered treatment-related: a grade 2 anaphylactoid reaction within 30 min of the first infusion. The patient withdrew; this was the only AE-related withdrawal. Hemoglobin concentrations, platelet counts, and spleen and liver volumes remained stable through 12 months. In conclusion, adult and pediatric patients with GD1, previously treated with imiglucerase, successfully transitioned to velaglucerase alfa, which was generally well tolerated and demonstrated efficacy over 12 months' treatment consistent with that observed in the velaglucerase alfa phase 3 clinical trial program. PMID:23339116

  1. Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease.

    PubMed

    Pastores, Gregory M; Turkia, Hadhami Ben; Gonzalez, Derlis E; Ida, Hiroyuki; Tantawy, Azza A G; Qin, Yulin; Qiu, Yongchang; Dinh, Quinn; Zimran, Ari

    2016-07-01

    Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naïve at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses. PMID:27282565

  2. Cost-effectiveness of epoetin alfa therapy for anemia of end-stage renal disease.

    PubMed

    Moran, L J; Carey, P; Johnson, C A

    1992-06-01

    The cost-effectiveness of epoetin alfa therapy for anemia in 20 patients with end-stage renal disease was retrospectively studied. Ten patients on continuous ambulatory peritoneal dialysis (CAPD) were given subcutaneous epoetin alfa as part of a multicenter, protocol-controlled study of the efficacy of epoetin alfa. Ten patients on in-center hemodialysis were given intravenous epoetin alfa as part of their routine clinical care. Change in hematocrit was used as the measure of effectiveness of epoetin alfa. Medication, laboratory, and transfusion costs were monitored for the six months preceding the initiation of epoetin alfa and the first six months of treatment. The cost of therapy increased for all patients by an average of $2722 +/- 1118; transfusion costs decreased, whereas medication and laboratory costs increased. Laboratory costs were significantly greater in CAPD patients than in hemodialysis patients during epoetin alfa therapy; no significant differences in medication costs or transfusion costs were noted between the groups. The mean increase in hematocrit for all patients was 7.4 volume percent. Following the initial change in hematocrit, further therapeutic response did not appear to be determined by increasing expenditures. Epoetin alfa was shown to be effective in treating anemia in patients with end-stage renal disease, but it was associated with higher costs of therapy.

  3. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-04-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate. PMID:16810345

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA

  5. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  6. DNA segregation by the bacterial actin AlfA during Bacillus subtilis growth and development.

    PubMed

    Becker, Eric; Herrera, Nick C; Gunderson, Felizza Q; Derman, Alan I; Dance, Amber L; Sims, Jennifer; Larsen, Rachel A; Pogliano, Joe

    2006-12-13

    We here identify a protein (AlfA; actin like filament) that defines a new family of actins that are only distantly related to MreB and ParM. AlfA is required for segregation of Bacillus subtilis plasmid pBET131 (a mini pLS32-derivative) during growth and sporulation. A 3-kb DNA fragment encoding alfA and a downstream gene (alfB) is necessary and sufficient for plasmid stability. AlfA-GFP assembles dynamic cytoskeletal filaments that rapidly turn over (t(1/2)< approximately 45 s) in fluorescence recovery after photobleaching experiments. A point mutation (alfA D168A) that completely inhibits AlfA subunit exchange in vivo is strongly defective for plasmid segregation, demonstrating that dynamic polymerization of AlfA is necessary for function. During sporulation, plasmid segregation occurs before septation and independently of the DNA translocase SpoIIIE and the chromosomal Par proteins Soj and Spo0J. The absence of the RacA chromosome anchoring protein reduces the efficiency of plasmid segregation (by about two-fold), suggesting that it might contribute to anchoring the plasmid at the pole during sporulation. Our results suggest that the dynamic polymerization of AlfA mediates plasmid separation during both growth and sporulation.

  7. New insights into erythropoietin and epoetin alfa: mechanisms of action, target tissues, and clinical applications.

    PubMed

    Weiss, Mitchell J

    2003-01-01

    Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.

  8. DNA segregation by the bacterial actin AlfA during Bacillus subtilis growth and development.

    PubMed

    Becker, Eric; Herrera, Nick C; Gunderson, Felizza Q; Derman, Alan I; Dance, Amber L; Sims, Jennifer; Larsen, Rachel A; Pogliano, Joe

    2006-12-13

    We here identify a protein (AlfA; actin like filament) that defines a new family of actins that are only distantly related to MreB and ParM. AlfA is required for segregation of Bacillus subtilis plasmid pBET131 (a mini pLS32-derivative) during growth and sporulation. A 3-kb DNA fragment encoding alfA and a downstream gene (alfB) is necessary and sufficient for plasmid stability. AlfA-GFP assembles dynamic cytoskeletal filaments that rapidly turn over (t(1/2)< approximately 45 s) in fluorescence recovery after photobleaching experiments. A point mutation (alfA D168A) that completely inhibits AlfA subunit exchange in vivo is strongly defective for plasmid segregation, demonstrating that dynamic polymerization of AlfA is necessary for function. During sporulation, plasmid segregation occurs before septation and independently of the DNA translocase SpoIIIE and the chromosomal Par proteins Soj and Spo0J. The absence of the RacA chromosome anchoring protein reduces the efficiency of plasmid segregation (by about two-fold), suggesting that it might contribute to anchoring the plasmid at the pole during sporulation. Our results suggest that the dynamic polymerization of AlfA mediates plasmid separation during both growth and sporulation. PMID:17139259

  9. Evaluating the transport layer of the ALFA framework for the Intel® Xeon Phi™ Coprocessor

    NASA Astrophysics Data System (ADS)

    Santogidis, Aram; Hirstius, Andreas; Lalis, Spyros

    2015-12-01

    The ALFA framework supports the software development of major High Energy Physics experiments. As part of our research effort to optimize the transport layer of ALFA, we focus on profiling its data transfer performance for inter-node communication on the Intel Xeon Phi Coprocessor. In this article we present the collected performance measurements with the related analysis of the results. The optimization opportunities that are discovered, help us to formulate the future plans of enabling high performance data transfer for ALFA on the Intel Xeon Phi architecture.

  10. Fast radio burst discovered in the Arecibo pulsar ALFA survey

    SciTech Connect

    Spitler, L. G.; Freire, P. C. C.; Lazarus, P.; Lee, K. J.; Cordes, J. M.; Chatterjee, S.; Wharton, R. S.; Brazier, A.; Hessels, J. W. T.; Lorimer, D. R.; McLaughlin, M. A.; Crawford, F.; Deneva, J. S.; Kaspi, V. M.; Karako-Argaman, C.; Allen, B.; Bogdanov, S.; Camilo, F.; Jenet, F. A.; Knispel, B.; and others

    2014-08-01

    Recent work has exploited pulsar survey data to identify temporally isolated, millisecond-duration radio bursts with large dispersion measures (DMs). These bursts have been interpreted as arising from a population of extragalactic sources, in which case they would provide unprecedented opportunities for probing the intergalactic medium; they may also be linked to new source classes. Until now, however, all so-called fast radio bursts (FRBs) have been detected with the Parkes radio telescope and its 13-beam receiver, casting some concern about the astrophysical nature of these signals. Here we present FRB 121102, the first FRB discovery from a geographic location other than Parkes. FRB 121102 was found in the Galactic anti-center region in the 1.4 GHz Pulsar Arecibo L-band Feed Array (ALFA) survey with the Arecibo Observatory with a DM = 557.4 ± 2.0 pc cm{sup –3}, pulse width of 3.0 ± 0.5 ms, and no evidence of interstellar scattering. The observed delay of the signal arrival time with frequency agrees precisely with the expectation of dispersion through an ionized medium. Despite its low Galactic latitude (b = –0.°2), the burst has three times the maximum Galactic DM expected along this particular line of sight, suggesting an extragalactic origin. A peculiar aspect of the signal is an inverted spectrum; we interpret this as a consequence of being detected in a sidelobe of the ALFA receiver. FRB 121102's brightness, duration, and the inferred event rate are all consistent with the properties of the previously detected Parkes bursts.

  11. Potential of epoetin alfa in patients in autologous blood donation programs for orthopedic surgery.

    PubMed

    McClelland, B

    1996-04-01

    The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

  12. Mortality Risk of Darbepoetin Alfa versus Epoetin Alfa in Patients with Chronic Kidney Disease: Systematic Review and Meta-Analysis

    PubMed Central

    Wilhelm-Leen, Emilee R.; Winkelmayer, Wolfgang C.

    2015-01-01

    Background Epoetin alfa (EPO) and darbepoetin alfa (EPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No studies have specifically compared the risks of hard study outcomes between EPO and DPO, including mortality. Methods We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) as well as of industry resources to identify all randomized trials comparing EPO versus DPO for the treatment of anemia in adult patients with chronic kidney disease including those requiring dialysis. We then summarized key characteristics and findings of these trials and performed a random effects meta-analysis of trials with at least 3 months duration to identify the summary odds ratio of mortality between patients randomized to DPO versus EPO. Results We identified 9 trials that met stated inclusion criteria. Overall, 2024 patients were included in the meta-analysis, of whom 126 died during follow up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomized to DPO versus EPO (OR=1.33; 95% CI 0.88-2.01). No treatment heterogeneity across studies was detected (Q-statistic = 4.60; P=0.80). Conclusions Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately-powered randomized trials, observational post-marketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents. PMID:25636816

  13. Elosulfase Alfa: a review of its use in patients with mucopolysaccharidosis type IVA (Morquio A syndrome).

    PubMed

    Lyseng-Williamson, Katherine A

    2014-10-01

    Elosulfase alfa (Vimizim(®)) is a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) that is lacking in patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). It is the first, and currently only, disease-specific treatment option for this very rare, progressively degenerative, autosomal-recessive lysosomal storage disorder. Enzyme replacement therapy with elosulfase alfa aims to restore GALNS activity, thereby preventing the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in lysosomal compartments of cells that results in the clinical manifestations of MPS IVA. In clinical trials in children and adults with MPS IVA, intravenous elosulfase alfa 2 mg/kg/week provided significant and sustained improvements in urinary levels of KS (a pharmacodynamic biomarker for the disease). In the key placebo-controlled, 24-week, phase 3 trial in patients with MPS IVA aged ≥5 years, elosulfase alfa 2 mg/kg/week significantly improved endurance [least squares mean placebo-adjusted change from baseline in 6-min walk test distance 22.5 m (95 % CI 4.0-40.9)]. Infusion-associated reactions, the primary tolerability issue associated with elosulfase alfa, are generally mild to moderate in severity, self-limiting, and manageable. In the absence of a cure, GALNS enzyme replacement therapy with elosulfase alfa is an important achievement in the treatment of MPS IVA.

  14. Charging properties of cassiterite (alfa-SnO2) surfaces

    SciTech Connect

    Rosenqvist, Jorgen K; Machesky, Michael L.; Vlcek, L.; Cummings, Peter T; Wesolowski, David J

    2009-01-01

    The acid-base properties of cassiterite (alfa-SnO2) surfaces at 10 50 C were studied using potentiometric titrations of powder suspensions in aqueous NaCl and RbCl media. The proton sorption isotherms exhibited common intersection points in the pH-range 4.0 to 4.5 at all conditions and the magnitude of charging was similar but not identical in NaCl and RbCl. The hydrogen bonding configuration at the oxide-water interface, obtained from classical Molecular Dynamics (MD) simulations, was analyzed in detail and the results were explicitly incorporated in calculations of protonation constants for the reactive surface sites using the revised MUSIC model. The calculations indicated that the terminal SnOH2 group is more acidic than the bridging Sn2OH group, with protonation constants (log KH) of 3.60 and 5.13 at 25 C, respectively. This is contrary to the situation on the isostructural alfa-TiO2 (rutile), apparently due to the difference in electronegativity between Ti and Sn. MD simulations and speciation calculations indicated considerable differences in the speciation of Na+ and Rb+, despite the similarities in overall charging. Adsorbed sodium ions are almost exclusively found in bidentate surface complexes, while adsorbed rubidium ions form comparable amounts of bidentate and tetradentate complexes. Also, the distribution of adsorbed Na+ between the different complexes shows a considerable dependence on surface charge density (pH), while the distribution of adsorbed Rb+ is almost independent of pH. A Surface Complexation Model (SCM) capable of accurately describing both the measured surface charge and the MD predicted speciation of adsorbed Na+/Rb+ was formulated. According to the SCM, the deprotonated terminal group (SnOH-0.40) and the protonated bridging group (Sn2OH+0.36) dominate the surface speciation over the entire pH-range (2.7 10), illustrating the ability of positively and negatively charged surface groups to coexist. Complexation of the medium cations

  15. Comparison of isotachophoresis, capillary zone electrophoresis and high-performance liquid chromatography for the determination of salbutamol, terbutaline sulphate and fenoterol hydrobromide in pharmaceutical dosage forms.

    PubMed

    Ackermans, M T; Beckers, J L; Everaerts, F M; Seelen, I G

    1992-01-31

    Reversed-phase high-performance liquid chromatography (RP-HPLC), isotachophoresis (ITP) and capillary zone electrophoresis (CZE) were applied to the determination of salbutamol, terbutaline sulphate and fenoterol hydrobromide in commercially available pharmaceutical dosage forms. The comparison showed that especially with the use of ITP, high concentrations of other charged sample components can disturb the separation process. If special attention is paid to ensure a complete separation, all methods give comparable results. For the regression lines of the calibration graphs, regression coefficients of at least ca. 0.999 and nearly zero intercepts are obtained with relative standard deviations of ca. 1-2% for peak area or zone lengths. By applying the different techniques, often different components of the sample matrix can be detected, i.e., a more complete impression of the sample composition can be obtained by using all the three techniques. PMID:1560101

  16. Perioperative epoetin alfa increases red blood cell mass and reduces exposure to transfusions: results of randomized clinical trials.

    PubMed

    Goldberg, M A

    1997-07-01

    To avoid the inherent risk of complications associated with perioperative allogeneic transfusion, preoperative autologous blood donation (PAD) is frequently employed by patients undergoing major elective surgical procedures. However, many patients are unable to donate a sufficient quantity of blood prior to surgery. Recent studies have shown that epoetin alfa (Procrit; Ortho-Biotech, Raritan, NJ) effectively increases red blood cell (RBC) mass when administered preoperatively and decreases the requirement for allogeneic transfusion. These studies also demonstrated that patients with baseline hemoglobin levels ranging from 10 to 13 g/dL have the highest risk for requiring allogeneic transfusions and appear to achieve the greatest benefit from epoetin alfa treatment. We evaluated several dosing regimens and schedules for perioperative epoetin alfa administration. In our initial study, the comparative efficacy of three different epoetin alfa regimens was assessed by hemoglobin concentration, hematocrit, and absolute reticulocyte counts. In addition, we analyzed the effect of accelerated erythropoiesis on iron indices and individual RBC hemoglobin content. Our study demonstrated that epoetin alfa is safe and effective in increasing RBC mass; however, iron stores considered sufficient for basal erythropoiesis may not optimally support the accelerated RBC production associated with epoetin alfa therapy. In a subsequent randomized multicenter trial, we compared weekly epoetin alfa dosing to daily dosing in patients undergoing elective major orthopedic surgery. The results of this study indicated that administering epoetin alfa on a weekly schedule for several weeks prior to surgery may be at least as effective and more convenient than perioperative daily epoetin alfa dosing.

  17. Taliglucerase alfa for the treatment of Gaucher's disease.

    PubMed

    Haddley, K

    2012-08-01

    Gaucher's disease is a rare inherited inborn error of metabolism caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase, GBA. Glucocerebrosidase is involved in the metabolism of the lipid metabolism-derived substrate, glucocerebroside. Accumulation of glucocerebroside substrate in macrophages, as a result of loss of enzyme function, leads to the formation of Gaucher cells causing hypertrophy of the spleen and liver, hematological disorders, skeletal malformations and the neurological symptoms characteristic of Gaucher's disease. The disease is subdivided into three types that differ in their symptoms, severity and prognosis. Patients of any age can be affected but those of a younger age have a poor prognosis often dying in infancy. As a genetic disorder the incidence of the disease is variable on a global scale. Enzyme replacement therapy is the therapy of choice and has demonstrated good efficacy in treating the visceral and skeletal symptoms of Gaucher's disease. A cost-effective plant-cell-derived human recombinant glucocerebrosidase, taliglucerase alfa, has been developed that demonstrated a promising safety and efficacy profile in phase I clinical trials and is currently in phase III and IV trials for the treatment of pediatric and adult patients with Gaucher's disease. PMID:22916340

  18. [The purification of the protein alternative to alfa-fetoprotein].

    PubMed

    Poltoranina, V S; Kuprina, N I; Eraĭzer, T L; Karamova, E R; Abelev, G I

    2007-01-01

    The subject of the study was the unidentified protein Ag A2/3, which is found in some cells of rat hepatoma McA RH7777 and their clones. The feature of this protein is that its expression is alternative to alfa-fetoprotein (AFP), i.e. Ag A2/3 is not found in cells and cell clones containing AFP, and vice versa. Ag A2/3 proved to be a cell stress protein--it was induced by heavy metal salts (Pb2+ and Cd2+) in the liver of adult rats and AFP+/A2/3(-) clones of hepatomas; the attenuation of AFP synthesis occurred simultaneously. This paper describes the preparation of Ag A2/3 for sequence analysis, and the scheme of Ag A2/3 purification. When trying to obtain a blot for sequencing it proved to be impossible to reveal the protein using McAb to Ag A2/3 after the transfer of separated proteins on PVDF. The reactivity of the antigen determinant was reestablished with blot processing on PVDF membrane with methanol and Twin 80. PMID:18084830

  19. Velaglucerase alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease.

    PubMed

    Ben Turkia, Hadhami; Gonzalez, Derlis E; Barton, Norman W; Zimran, Ari; Kabra, Madhulika; Lukina, Elena A; Giraldo, Pilar; Kisinovsky, Isaac; Bavdekar, Ashish; Ben Dridi, Marie-Françoise; Gupta, Neerja; Kishnani, Priya S; Sureshkumar, E K; Wang, Nan; Crombez, Eric; Bhirangi, Kiran; Mehta, Atul

    2013-03-01

    Enzyme replacement therapy for Gaucher disease (GD) has been available since 1991. This study compared the efficacy and safety of velaglucerase alfa with imiglucerase, the previous standard of care. A 9-month, global, randomized, double-blind, non-inferiority study compared velaglucerase alfa with imiglucerase (60 U/kg every other week) in treatment-naïve patients aged 3-73 years with anemia and either thrombocytopenia or organomegaly. The primary endpoint was the difference between groups in mean change from baseline to 9 months in hemoglobin concentration. 35 patients were randomized: 34 received study drug (intent-to-treat: 17 per arm), 20 were splenectomized. Baseline characteristics were similar in the two groups. The per-protocol population included 15 patients per arm. The mean treatment difference for hemoglobin concentration from baseline to 9 months (velaglucerase alfa minus imiglucerase) was 0.14 and 0.16 g/dL in the intent-to-treat and per-protocol populations, respectively. The lower bound of the 97.5% one-sided confidence interval in both populations lay within the pre-defined non-inferiority margin of -1.0 g/dL, confirming that velaglucerase alfa is non-inferior to imiglucerase. There were no statistically significant differences in the secondary endpoints. Most adverse events were mild to moderate. No patient receiving velaglucerase alfa developed antibodies to either drug, whereas four patients (23.5%) receiving imiglucerase developed IgG antibodies to imiglucerase, which were cross-reactive with velaglucerase alfa in one patient. This study demonstrates the efficacy and safety of velaglucerase alfa compared with imiglucerase in adult and pediatric patients with GD clinically characterized as Type 1. Differences in immunogenicity were also observed. PMID:23400823

  20. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology.

    PubMed

    Grabowski, Gregory A; Golembo, Myriam; Shaaltiel, Yoseph

    2014-05-01

    Gaucher disease (GD) is a rare, genetic lysosomal storage disorder caused by functional defects of acid β-glucosidase that results in multiple organ dysfunction. Glycosylation of recombinant acid human β-glucosidase and exposure of terminal mannose residues are critical to the success of enzyme replacement therapy (ERT) for the treatment of visceral and hematologic manifestations in GD. Three commercially available ERT products for treatment of GD type 1 (GD1) include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems and require production glycosylation modifications to expose terminal α-mannose residues, which are needed for mannose receptor-mediated uptake by target macrophages. Such modifications add to production costs. Taliglucerase alfa is a plant cell-expressed acid β-glucosidase approved in the United States and other countries for ERT in adults with GD1. A plant-based expression system, using carrot root cell cultures, was developed for production of taliglucerase alfa and does not require additional processing for postproduction glycosidic modifications. Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-naïve patients with symptomatic GD1, and for such patients previously treated with imiglucerase. These included significant improvements in organomegaly and hematologic parameters as early as 6months, and maintenance of achieved therapeutic values in previously treated patients. Ongoing clinical trials will further characterize the long-term efficacy and safety of taliglucerase alfa in more diverse patient populations, and may help to guide clinical decisions for achieving optimal outcomes for patients with GD1. PMID:24630271

  1. Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs.

    PubMed

    Agersø, H; Stennicke, H R; Pelzer, H; Olsen, E N; Merricks, E P; Defriess, N A; Nichols, T C; Ezban, M

    2012-11-01

    The objective of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the new recombinant FVIII compound turoctocog alfa and a Glyco-PEGylated FVIII derivative thereof (N8-GP) in Haemophilia A dogs. Six haemophilic dogs divided into two groups were included in the study. Each dog was administered a dose of 125 U kg(-1) , blood samples were collected at predetermined time points for both pharmacokinetic (FVIII measured by one-stage aPTT assay) and pharmacodynamic [whole blood clotting time (WBCT)] evaluations. After intravenous administration to haemophilic dogs, the plasma concentration at the first sampling point was comparable for turoctocog alfa and N8-GP, and the clearance was estimated to be 6.5 and 3.9 mL h(-1) kg(-1) for turoctocog alfa and N8-GP respectively. Both turoctocog alfa and N8-GP were able to reduce the WBCT time to normal levels (<20 min), however, the reduced clearance was reflected in the WBCT, which returned to baseline at a later time point for N8-GP as compared with dogs dosed with turoctocog alfa. The clearance was 40% reduced for N8-GP as compared with turoctocog alfa. Simulations of a multiple dosing regimen in dogs, suggest that to maintain WBCT <20 min N8-GP can be dosed at reduced intervals, e.g. with 4 days between doses, whereas turoctocog alfa will have to be dosed with 2½ day between doses. Data thereby supports N8-GP as an alternative to standard rFVIII replacement therapy, with a more convenient dosing regimen.

  2. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    PubMed

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  3. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    PubMed

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  4. Early Treatment with Alglucosidase Alfa Prolongs Long Term Survival of Infants with Pompe Disease

    PubMed Central

    Kishnani, Priya S.; Corzo, Deya; Leslie, Nancy D.; Gruskin, Daniel; van der Ploeg, Ans; Clancy, John P.; Parini, Rosella; Morin, Gilles; Beck, Michael; Bauer, Mislen S.; Jokic, Mikael; Tsai, Chen-En; Tsai, Brian W.H.; Morgan, Claire; O’Meara, Tara; Richards, Susan; Tsao, Elisa C.; Mandel, Hanna

    2011-01-01

    In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 months old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n=8) or 40 mg/kg biweekly (n=8), for up to a total of 3 years. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 months. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, as compared to an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 mg/kg and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival, and improved cardiomyopathy. PMID:19542901

  5. Dornase alfa is well tolerated: data from the epidemiologic registry of cystic fibrosis.

    PubMed

    McKenzie, S G; Chowdhury, S; Strandvik, B; Hodson, M E

    2007-10-01

    After closure of the Epidemiologic Registry of Cystic Fibrosis (ERCF), a comprehensive safety analysis of dornase alfa was performed. A planned subanalysis focused on children under 5 years old. Reported serious adverse events (SAEs) were assigned a preferred term and ascribed to a specific organ system. Possible serious adverse reactions to dornase alfa (SADRs) were identified by reporting clinics. Twenty-eight of 15,865 SAEs (0.18%), occurring in 26 of 6,829 patients ever treated with dornase alfa (0.38%), and no deaths were reported as possible SADRs: most were typical complications of cystic fibrosis (CF). There was no evidence of any unrecognized risk of treatment. During 24,586 patient-years of follow-up (FU) of ever-treated patients, SAEs (mostly typical respiratory complications of CF) were more frequent on-treatment (0.4999/patient-year; 95% CI 0.4921-0.5076) than off-treatment (0.3889; 0.3787-0.3992). This was likely caused by within-patient prescription bias. During 655 patient-years of FU in 328 ever-treated patients under 5 years old, SAEs (mostly pulmonary exacerbations of CF) were slightly less frequent during treatment: 0.2911 (0.2367-0.3455) versus 0.3563 (0.3086-0.4040; ns). Results confirm the safety of dornase alfa in CF patients of all ages. Children under 5 years old tolerate dornase alfa at least as well as older patients.

  6. Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; Nambo, M J; García, E L

    1998-08-01

    We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease. PMID:9711927

  7. Epoetin alfa plus autologous blood donation in patients with a low hematocrit scheduled to undergo orthopedic surgery.

    PubMed

    Tryba, M

    1996-04-01

    A low predonation hematocrit (Hct) can preclude the collection of sufficient autologous blood (AB) to meet the transfusion requirements of patients scheduled for orthopedic surgery. Subcutaneous (s.c.) administration of epoetin alfa, in conjunction with intravenous (i.v.) iron supplementation, has proved effective for the facilitation of AB donation by such patients. Compared with untreated controls and patients treated with i.v. iron alone, epoetin alfa 50 to 150 IU/kg SC plus i.v. iron twice weekly for 3 weeks prior to surgery significantly increased total red blood cell (RBC) production (P < .01) and the volume of RBCs donated (P < .05). Epoetin alfa was particularly effective in females and patients with a predicted blood volume (PBV) less than 5 L. Treatment with epoetin alfa led to an increase (albeit nonsignificant) in the number of AB units predonated compared with i.v. iron alone. However, in patients with a PBV less than 5 L, a substantially greater percentage of epoetin alfa-treated patients donated > or = 4 AB units (80% v 30%). Allogeneic blood requirements were reduced, albeit not significantly (P = .051), in patients treated with epoetin alfa. However, in comparison with untreated controls, there was a significant reduction in the mean volume of allogeneic blood transfused per transfused patient in the epoetin alfa groups. The optimum s.c. dose of epoetin alfa in patients with a low predonation Hct scheduled for orthopedic surgery appears to be between 100 and 150 IU/kg twice weekly for 3 weeks.

  8. Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

    PubMed

    Saccà, Francesco; Piro, Raffaele; De Michele, Giuseppe; Acquaviva, Fabio; Antenora, Antonella; Carlomagno, Guido; Cocozza, Sergio; Denaro, Alessandra; Guacci, Anna; Marsili, Angela; Perrotta, Gaetano; Puorro, Giorgia; Cittadini, Antonio; Filla, Alessandro

    2011-03-01

    Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.

  9. Successful Within-patient Dose Escalation of Olipudase Alfa in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Soran, Handrean; Diaz, George A.; Lippa, Natalie; Thurberg, Beth L.; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F.; Puga, Ana Cristina

    2015-01-01

    Background Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Methods Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. Results All patients successfully reached 3.0 mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4 hours across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. Conclusions This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. PMID:26049896

  10. VizieR Online Data Catalog: Arecibo Pulsar-ALFA (PALFA) survey. IV. (Lazarus+, 2015)

    NASA Astrophysics Data System (ADS)

    Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Karako-Argaman, C.; Kaspi, V. M.; Lynch, R.; Madsen, E.; Patel, C.; Ransom, S. M.; Scholz, P.; Swiggum, J.; Zhu, W. W.; Allen, B.; Bogdanov, S.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R.; Freire, P. C. C.; Jenet, F. A.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lorimer, D. R.; Lyne, A. G.; McLaughlin, M. A.; Siemens, X.; Spitler, L. G.; Stairs, I. H.; Stovall, K.; Venkataraman, A.

    2016-02-01

    The Arecibo Pulsar-ALFA (PALFA) survey observations have been restricted to the two regions of the Galactic plane (|b|<5°) visible from the Arecibo observatory, the inner Galaxy (32°<~l<~77°), and the outer Galaxy (168°<~l<~214°). Integration times are 268s and 180s for inner and outer Galaxy observations, respectively. Observations conducted with the 7-beam Arecibo L-band Feed Array (ALFA) receiver of the Arecibo Observatory William E. Gordon 305m Telescope have a bandwidth of 322MHz centered at 1375MHz. PALFA survey data have been recorded with the Mock spectrometers since 2009. (2 data files).

  11. Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial.

    PubMed

    Bosques-Padilla, Francisco; Trejo-Estrada, Rafael; Campollo-Rivas, Octaivio; Cortez-Hernández, Carlos; Dehesa-Violante, Margarita; Maldonado-Garza, Héctor; Pérez-Gómez, Rául; Cabrera-Valdespino, Armando

    2003-01-01

    Treatment with polyethylene glycol-modified interferon alfa-2a (peginterferon) alone produces significantly higher sustained antiviral responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Thirty-two patients were randomly assigned to treatment, and received at least one dose of medication consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1,000 or 1,200 mg, depending on body weight) (n = 14), weekly peginterferon alfa-2a plus daily placebo (n = 6), or three million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks (n = 12). More patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than patients who received interferon alfa-2b plus ribavirin (7/14 vs. 4/12) or peginterferon alfa-2a plus placebo (0/6). The overall safety profiles of the three treatment regimens were similar. In conclusion, for patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained viral reduction compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone. PMID:15115965

  12. The Synchrony and Diachrony of Bosnian-Croatian-Serbian Adjectival Long-Form Allomorphy (ALFA)

    ERIC Educational Resources Information Center

    Pennington, James Joshua

    2010-01-01

    In Bosnian-Croatian-Serbian (BCS), the gentive (G) and dative/locative (DL) cases exhibit adjectival long-form allomorphy (ALFA). The genitive -"og" -"oga" and the DL -"om" -"ome" -"omu" stand in free variation, inasmuch as when one form is substituted for another the truth value of an utterance remains unchanged. Some sociolinguists (particularly…

  13. Treatment of cancer-related anemia with epoetin alfa: a review.

    PubMed

    Ferrario, Erminia; Ferrari, Leonardo; Bidoli, Paolo; De Candis, Daniela; Del Vecchio, Michele; De Dosso, Sara; Buzzoni, Roberto; Bajetta, Emilio

    2004-10-01

    Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.

  14. Asfotase alfa: enzyme replacement for the treatment of bone disease in hypophosphatasia.

    PubMed

    Hofmann, C; Seefried, L; Jakob, F

    2016-05-01

    Hypophosphatasia (HPP) is a rare disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP, TNSALP) gene. HPP causes a multisystemic syndrome with a predominant bone phenotype. The clinical spectrum ranges from high lethality in early onset (<6 months) HPP to mild late-onset syndromes. HPP management so far has been only supportive. Subcutaneous asfotase alfa, a first-in-class bone-targeted human TNAP enzyme replacement therapy, is the first compound to be approved for long-term treatment of bone manifestations in pediatric-onset HPP. In noncomparative clinical trials (treatment up to 7 years), this treatment was associated with skeletal, respiratory and functional improvement in perinatal, infantile and childhood-onset HPP. Compared with age-matched historical controls, patients with life-threatening perinatal and infantile HPP treated with asfotase alfa had substantially improved bone mineralization, survival and ventilation-free survival. In childhood HPP, asfotase alfa improved growth, gross motor function, strength and agility and decreased pain. The compound was well tolerated and most adverse events were of mild to moderate intensity. To date, data and experience concerning its efficacy and safety in long-term treatment are not yet available. Further studies to evaluate risks and benefits of enzyme replacement therapy with asfotase alfa in adults are in progress and are also strongly needed. PMID:27376160

  15. Switch from epoetin to darbepoetin alfa in hemodialysis: dose equivalence and hemoglobin stability

    PubMed Central

    Arrieta, Javier; Moina, Iñigo; Molina, José; Gallardo, Isabel; Muñiz, María Luisa; Robledo, Carmen; García, Oscar; Vidaur, Fernando; Muñoz, Rosa Inés; Iribar, Izaskun; Aguirre, Román; Maza, Antonio

    2014-01-01

    Aim The objective of the study reported here was to describe dose equivalence and hemoglobin (Hb) stability in a cohort of unselected hemodialysis patients who were switched simultaneously from epoetin alfa to darbepoetin alfa. Methods This was a multicenter, observational, retrospective study in patients aged ≥18 years who switched from intravenous (IV) epoetin alfa to IV darbepoetin alfa in October 2007 (Month 0) and continued on hemodialysis for at least 24 months. The dose was adjusted to maintain Hb within 1.0 g/dL of baseline. Results We included 125 patients (59.7% male, mean [standard deviation (SD)] age 70.4 [13.4] years). No significant changes were observed in Hb levels (mean [SD] 11.9 [1.3] g/dL, 12.0 [1.5], 12.0 [1.5], and 12.0 [1.7] at Months −12, 0, 12 and 24, respectively, P=0.409). After conversion, the erythropoiesis-stimulating agent (ESA) dose decreased significantly (P<0.0001), with an annual mean of 174.7 (88.7) international units (IU)/kg/week for epoetin versus 95.7 (43.4) (first year) and 91.4 (42.7) IU/kg/week (second year) for darbepoetin (65% and 64% reduction, respectively). The ESA resistance index decreased from 15.1 (8.5) IU/kg/week/g/dL with epoetin to 8.1 (3.9) (first year) and 7.9 (4.0) (second year) with darbepoetin (P<0.0001). The conversion rate was 354:1 in patients requiring high (>200 IU/kg/week) doses of epoetin and 291:1 in patients requiring low doses. Conclusion In patients on hemodialysis receiving ESAs, conversion from epoetin alfa to darbepoetin alfa was associated with an approximate and persistent reduction of 65% of the required dose. To maintain Hb stability, a conversion rate of 300:1 seems to be appropriate for most patients receiving low doses of epoetin alfa (≤200 IU/kg/week), while 350:1 would be better for patients receiving higher doses. PMID:25336984

  16. A new hydrophilic interaction liquid chromatographic (HILIC) procedure for the simultaneous determination of pseudoephedrine hydrochloride (PSH), diphenhydramine hydrochloride (DPH) and dextromethorphan hydrobromide (DXH) in cough-cold formulations.

    PubMed

    Ali, Mohammed Shahid; Ghori, Mohsin; Rafiuddin, Syed; Khatri, Aamer Roshanali

    2007-01-01

    A new HILIC method has been developed for the simultaneous determination of pseudoephedrine hydrochloride (PSH), diphenhydramine hydrochloride (DPH) and dextromethorphan hydrobromide (DXH) in cough-cold syrup. Mobile phase consists of methanol:water (containing 6.0 g of ammonium acetate and 10 mL of triethylamine per liter, pH adjusted to 5.2 with orthophosphoric acid), 95:5 (v/v). Column containing porous silica particles (Supelcosil LC-Si, 25 cm x 4.6 mm, 5 microm) is used as stationary phase. Detection is carried out using a variable wavelength UV-vis detector at 254 nm for PSH and DPH, and at 280 nm for DXH. Solutions are injected into the chromatograph under isocratic condition at constant flow rate of 1.2 mL/min. Linearity range and percent recoveries for PSH, DPH and DXH were 150-600, 62.5-250, 75-300 microg/mL and 100.7%, 100.1% and 100.8%, respectively. Method is stability indicating and excipients like saccharin sodium, sodium citrate, flavour and sodium benzoate did not interfere in the analysis. Compounds elute in order of increasing ionization degree caused by cation-exchange mechanism in a run time of less than 15 min. Mobile phase pH is manipulated to regulate ionization and ion-exchange interaction and thereby retention of compounds. PMID:16887317

  17. Lattice potential energy and standard molar enthalpy in the formation of 1—dodecylamine hydrobromide (1-C12H25NH3·Br)(s)

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Pu; Di, You-Ying; Dan, Wen-Yan; He, Dong-Hua; Kong, Yu-Xia; Yang, Wei-Wei

    2011-02-01

    This paper reports that 1-dodecylamine hydrobromide (1-C12H25NH3·Br)(s) has been synthesized using the liquid phase reaction method. The lattice potential energy of the compound 1-C12H25NH3·Br and the ionic volume and radius of the 1-C12H25NH3+ cation are obtained from the crystallographic data and other auxiliary thermodynamic data. The constant-volume energy of combustion of 1-C12H25NH3·Br(s) is measured to be ΔcUmo(1-C12H25NH3·Br, s) = -(7369.03±3.28) kJ·mol-1 by means of an RBC-II precision rotating-bomb combustion calorimeter at T = (298.15±0.001) K. The standard molar enthalpy of combustion of the compound is derived to be ΔcHmo(1-C12H25NH3·Br, s) = -(7384.52±3.28) kJ·mol-1 from the constant-volume energy of combustion. The standard molar enthalpy of formation of the compound is calculated to be ΔfHmo(1-C12H25NH3·Br, s)=-(1317.86±3.67) kJ·mol-1 from the standard molar enthalpy of combustion of the title compound and other auxiliary thermodynamic quantities through a thermochemical cycle.

  18. Studies on the growth, structural, thermal, mechanical and optical properties of the semiorganic nonlinear optical crystal L-glutamic acid hydrobromide

    NASA Astrophysics Data System (ADS)

    Dhanasekaran, P.; Srinivasan, K.

    2013-07-01

    Single crystals of optically significant L-glutamic acid hydrobromide were grown from aqueous solutions and their various properties were characterized. The title compound was synthesized with stoichiometric ratio 1:1, purified by recrystallization, confirmed by powder X-ray diffraction and its solubility in double distilled water in the temperature range 30-80 °C was determined by the gravimetric method. Large dimensional (45×26×14 mm3) optically transparent single crystal of the compound was grown by a controlled slow cooling method combined with the reversible seed rotation technique. The morphological importance of the grown crystal was studied in accordance with equilibrium morphology. Samples of the grown crystal were subjected to single crystal X-ray diffraction study for structural analysis, Fourier transform infrared spectroscopy for functional group analysis, TG-DTA/DSC for thermal analysis, Vickers microhardness study for mechanical strength, UV-vis-NIR spectral analysis for optical transparency and the Kurtz powder method for SHG efficiency of the grown crystal. Results indicate that the grown crystal has significant improvement in its thermal, optical and SHG properties when compared to pure L-glutamic acid polymorphs.

  19. Ovulation induction with minimal dose of follitropin alfa: a case series study

    PubMed Central

    2011-01-01

    Background Gonadotropins are used in ovulation induction (OI) for patients with anovulatory infertility. Pharmacologic OI is associated with risks of ovarian hyperstimulation syndrome and multiple pregnancy. Treatment protocols that minimize these risks by promoting monofollicular development are required. A starting dose of 37.5 IU/day follitropin alfa has been used in OI, particularly among women at high risk of multifollicular development and multiple pregnancy. A retrospective case series study was performed to evaluate rates of monofollicular development and singleton pregnancy following standard treatment with 37.5 IU/day follitropin alfa. Methods Spanish centers that had performed at least five OI cycles during 2008 using 37.5 IU/day follitropin alfa as a starting dose were invited to participate. Data could be provided from any cycle performed in 2008 (up to a maximum of 12 consecutive cycles per site). Case report forms were collected during April-November 2009 and reviewed centrally. Descriptive statistics were obtained from all cases, and follicular development and clinical pregnancy rates assessed. Potential associations of age and body mass index with follicular development and clinical pregnancy were assessed using univariate correlation analyses. Results Thirty centers provided data on 316 cycles of OI using a starting dose of 37.5 IU/day follitropin alfa. Polycystic ovary syndrome was the cause of anovulatory infertility in 217 (68.7%) cases. Follitropin alfa at 37.5 IU/day was sufficient to achieve ovarian stimulation in 230 (72.8%) cycles. A single follicle ≥16 mm in diameter developed in 193 cycles (61.1%; 95% confidence interval [CI] 55.7-66.4%). Seventy-eight women (24.7%; 95% CI 19.9-29.5%) became pregnant: 94.9% singleton and 5.1% twin pregnancies. Fourteen started cycles (4.4%) were cancelled, mainly due to poor response. Univariate correlation analyses detected weak associations. Conclusions Monofollicular growth rate was comparable with

  20. The peripheral innervation of the gill of the marine mollusc demonstrated by the aluminium-formaldehyde (ALFA) histofluorescence method.

    PubMed

    Catapane, E J

    1982-01-01

    The aluminium-formaldehyde (ALFA) histofluorescence method was used to study the innervation of the gill of the marine bivalve mollusc Mytilus edulis and the results were contrasted with those obtained with the standard formaldehyde-induced-fluorescence (FIF) method. The ALFA method produced more fluorescing structures than the FIF method, thus revealing fine branches of the branchial nerve running beneath the gill epithelium which previously remained undetected. This study of marine invertebrates. PMID:7105160

  1. Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment

    PubMed Central

    Dewamitta, Sita R.; Russell, Megan R.; Nandurkar, Harshal; Walkley, Carl R.

    2013-01-01

    Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansion. Both agents induced an expansion of the colony-forming unit-erythroid populations. However, unlike erythropoietin, darbepoietin-alfa did not impair bone marrow B lymphopoiesis. Strikingly the bone loss observed with erythropoietin was not apparent following darbepoietin-alfa treatment. This analysis demonstrates that whilst darbepoietin-alfa has similar in vivo erythropoietic potency to erythropoietin, it preserves the bone marrow microenvironment. Thus erythropoietin and darbepoietin-alfa manifest different action showing that erythropoiesis stimulating agents have differential non-erythroid effects dependent on their duration of action. PMID:23242598

  2. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.

    PubMed

    Powers, Kimberly A; Dixit, Narendra M; Ribeiro, Ruy M; Golia, Preeti; Talal, Andrew H; Perelson, Alan S

    2003-01-01

    Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b. PMID:12934163

  3. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  4. Epoetin alfa for protection of metabolic and exercise capacity in cancer patients.

    PubMed

    Daneryd, Peter

    2002-06-01

    A controlled clinical trial was conducted to evaluate the use of epoetin alfa in cachectic patients with solid tumors who were not receiving chemotherapy to determine if increasing hemoglobin (Hb) resulted in increased exercise capacity, metabolism, and energy efficiency during a maximum work load. The randomized, prospective study included 108 patients who received oral indomethacin 50 mg twice daily (n = 58; control group), or oral indomethacin 50 mg twice daily with epoetin alfa 4,000 to 10,000 IU by subcutaneous injection 3 times weekly (n = 50; study group). Patients randomized to the study group received epoetin alfa only when Hb decreased below 12.8 g/dL for men and 12.0 g/dL for women. Mean Hb levels in the study group were significantly (P <.0001) improved overall compared with the control group, with significant differences seen between groups after 2 to 4 months (P <.003), 6 to 8 months (P <.01), and 10 to 30 months (P <.01). Mean inflammatory variables including serum albumin, erythrocyte sedimentation rate, and C-reactive protein were significantly (P <.02) changed in the study group compared with the control group (ie, the control group had more inflammation). Significantly lower mean body weight (P <.05) and resting energy expenditure (P <.007) were recorded for patients in the control group versus the study group. The study group showed significantly greater mean exercise capacity (P <.0001), mean oxygen uptake (P <.01), mean CO(2) production (P <.009), and respiration (P <.03). These results demonstrate that early use of epoetin alfa prevents anemia in patients with progressive cancer who are not receiving chemotherapy. Normalization of Hb levels resulted in improved whole-body metabolism and energy efficiency, which is associated with greater exercise capacity and better daily quality of life.

  5. Cost-effectiveness impact of iron dextran on hemodialysis patients' use of epoetin alfa and blood.

    PubMed

    Driver, P S

    1998-12-15

    The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

  6. Epoetin alfa. A bloodless approach for the treatment of perioperative anemia.

    PubMed

    Faris, P M; Ritter, M A

    1998-12-01

    Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.

  7. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials

    PubMed Central

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-01-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc. PMID:25801797

  8. Cost of managing anemia with and without prophylactic epoetin alfa therapy in breast cancer patients receiving combination chemotherapy.

    PubMed

    Meadowcroft, A M; Gilbert, C J; Maravich-May, D; Hayward, S L

    1998-09-15

    The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

  9. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil

    PubMed Central

    2013-01-01

    Background Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures. The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario. Methods To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian

  10. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease.

    PubMed

    van Dussen, L; Zimran, A; Akkerman, E M; Aerts, J M F G; Petakov, M; Elstein, D; Rosenbaum, H; Aviezer, D; Brill-Almon, E; Chertkoff, R; Maas, M; Hollak, C E M

    2013-03-01

    Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). As bone disease is one of the most debilitating features of GD, quantification of bone marrow involvement is important for monitoring the response to treatment. Therefore, bone marrow fat fraction (Ff) measured by quantitative chemical shift imaging (QCSI) was included as exploratory parameter to evaluate bone marrow response in treatment naïve GD patients participating in a double-blind, randomized phase III study. Eight GD patients with intact spleens were treated with 30 or 60U/kg biweekly. Ff results were compared to outcomes in 15 untreated Dutch GD patients with a follow-up interval of 1year. Five taliglucerase alfa treated patients had a Ff below the threshold that relates to complication risk (<0.23) at baseline (median (n=8) 0.19, range 0.11-0.35). Ff significantly increased compared to baseline (p=0.012) and compared to untreated patients (p=0.005), already after 1year of follow-up with further improvement up to 36months. In four patients with the lowest Ff, the higher dose resulted in increases above 0.23 within 1year. All patients had sustained improvements in all other parameters. There was no influence of antibodies on response parameters. Treatment with taliglucerase alfa results in significant increases in lumbar spine fat fractions, which indicates clearance of Gaucher cells from the bone marrow. PMID:23199589

  11. Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C.

    PubMed

    Saleem, Ayesha

    2016-05-01

    Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible. PMID:27183950

  12. Effectiveness of corifollitropin alfa used for ovarian stimulation of poor responder patients

    PubMed Central

    Selman, Helmy; Rinaldi, Leonardo

    2016-01-01

    Purpose To evaluate the efficiency and efficacy of corifollitropin alfa (follicle-stimulating hormone–carboxy terminal peptide) in the treatment of poor responder patients. Methods A total of 85 poor responder patients with a mean age 40.2±3.9 years entered our assisted fertilization program. The patients were prospectively randomized into two groups based on the ovarian stimulation regimen used: group A (study group) (n=42) received clomiphene citrate and corifollitropin alfa for the first 7 days of stimulation followed by recombinant follicle stimulating hormone (rFSH) in a gonadotropin-releasing hormone antagonist protocol, and group B (control group) (n=43) received clomiphene citrate and a daily injection of rFSH in a gonadotropin-releasing hormone antagonist protocol. We analyzed the stimulation outcome, the number of retrieved oocytes, cleaving embryos, and pregnancy and implantation rates as well. Results Comparable results were observed between the two groups in terms of demographic data, stimulation outcome, and the number of canceled cycles. There were no differences evident between groups A and B with respect to the number of retrieved oocytes (3.0±0.8 and 2.7±0.7, respectively) and the number of cleaving embryos (1.8±0.6 and 1.7±0.7, respectively). Higher, though not statistically significant, differences were observed in favor of group A compared to group B in terms of pregnancy rate per cycle (19% and 16.3%, respectively), pregnancy rate per transfer (21.6% and 17.9%, respectively), and implantation rate (14.7% and 13.4%, respectively). Also, miscarriage rate was similar between patients treated with corifollitropin alfa and those treated with daily rFSH injection (12.5% and 14.2%, respectively). Conclusion The results show that ovarian stimulation with corifollitropin alfa appears to be as efficacious and efficient as daily injection rFSH regimen to treat patients with poor ovarian response. PMID:27799826

  13. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders

    PubMed Central

    Wang, Huai-Ling; Lai, Hsing-Hua; Chuang, Tzu-Hsuan; Shih, Yu-Wei; Huang, Shih-Chieh; Lee, Meng-Ju; Chen, Shee-Uan

    2016-01-01

    The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed. PMID:27100388

  14. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  15. ARECIBO PULSAR SURVEY USING ALFA: PROBING RADIO PULSAR INTERMITTENCY AND TRANSIENTS

    SciTech Connect

    Deneva, J. S.; Cordes, J. M.; McLaughlin, M. A.; Lorimer, D. R.; Edel, S.; Kondratiev, V. I.; Nice, D. J.; Crawford, F.; Bhat, N. D. R.; Camilo, F.; Champion, D. J.; Freire, P. C. C.; Hessels, J. W. T.; Jenet, F. A.; Kasian, L.; Kaspi, V. M.; Lazarus, P.; Stairs, I. H.; Kramer, M.; Ransom, S. M.

    2009-10-01

    We present radio transient search algorithms, results, and statistics from the ongoing Arecibo Pulsar ALFA (PALFA) survey of the Galactic plane. We have discovered seven objects through a search for isolated dispersed pulses. All of these objects are Galactic and have measured periods between 0.4 and 4.7 s. One of the new discoveries has a duty cycle of 0.01%, smaller than that of any other radio pulsar. We discuss the impact of selection effects on the detectability and classification of intermittent sources, and compare the efficiencies of periodicity and single-pulse (SP) searches for various pulsar classes. For some cases we find that the apparent intermittency is likely to be caused by off-axis detection or a short time window that selects only a few bright pulses and favors detection with our SP algorithm. In other cases, the intermittency appears to be intrinsic to the source. No transients were found with DMs large enough to require that they originate from sources outside our Galaxy. Accounting for the on-axis gain of the ALFA system, as well as the low gain but large solid-angle coverage of far-out sidelobes, we use the results of the survey so far to place limits on the amplitudes and event rates of transients of arbitrary origin.

  16. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma

    PubMed Central

    Wahl, R.U.; Braunschweig, T.; Ghassemi, A.; Rübben, A.

    2016-01-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1–2×106 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  17. Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party.

    PubMed

    Angus, Derek C

    2012-01-01

    Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response. PMID:22309988

  18. Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa

    PubMed Central

    Su, Kim; Donaldson, Emma; Sharma, Reena

    2016-01-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with lipid-modifying agents does not ameliorate disease progression. Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications. Sebelipase alfa (Kanuma) is a recombinant human LAL protein and the first enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter. Sebelipase alfa has received marketing authorization in the United States and Europe as long-term therapy for all affected individuals. The availability of enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians. PMID:27799810

  19. Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party.

    PubMed

    Angus, Derek C

    2012-01-01

    Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.

  20. Demonstrating the stability of albinterferon alfa-2b in the presence of silicone oil.

    PubMed

    Auge, Kristin B; Blake-Haskins, Angela W; Devine, Sean; Rizvi, Sophia; Li, Yi-Ming; Hesselberg, Mark; Orvisky, Eduard; Affleck, Richard P; Spitznagel, Thomas M; Perkins, Melissa D

    2011-12-01

    Silicone oil is often used to decrease glide forces in prefilled syringes and cartridges, common primary container closures for biopharmaceutical products. Silicone oil has been linked to inducing protein aggregation (Diabet Med 1989;6:278; Diabet Care 1987;10:786-790), leading to patient safety and immunogenicity concerns. Because of the silicone oil application process (Biotech Adv 2007;25:318-324), silicone oil levels tend to vary between individual container closures. Various silicone oil levels were applied to a container closure prior to filling and lyophilization of an albumin and interferon alfa-2b fusion protein (albinterferon alfa-2b). Data demonstrated that high silicone oil levels in combination with intended and stress storage conditions had no impact on protein purity, higher order structure, stability trajectory, or biological activity. Subvisible particulate analysis (1-10 µm range) from active and placebo samples from siliconized glass barrels showed similar particle counts. Increases in solution turbidity readings for both active and placebo samples correlated well with increases in silicone oil levels, suggesting that the particles in solution are related to the presence of silicone oil and not large protein aggregates. Results from this study demonstrate that silicone oil is not always detrimental to proteins; nevertheless, assessing the impact of silicone oil on a product case-by-case basis is still recommended. PMID:21780119

  1. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  2. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

    PubMed

    Wahl, R U; Braunschweig, T; Ghassemi, A; Rübben, A

    2016-04-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  3. Longer-term Outcomes of Darbepoetin Alfa Versus Epoetin Alfa in Patients With ESRD Initiating Hemodialysis: A Quasi-experimental Cohort Study

    PubMed Central

    Winkelmayer, Wolfgang C.; Chang, Tara I.; Mitani, Aya A.; Wilhelm-Leen, Emilee R.; Ding, Victoria; Chertow, Glenn M.; Brookhart, M. Alan; Goldstein, Benjamin A.

    2015-01-01

    Background Adequately-powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. Study Design Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis in facilities (almost) exclusively using DPO versus EPO. Setting & Participants Non-chain US hemodialysis facilities; each facility switching from EPO to DPO (2003–2010) was matched on location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis in these facilities were assigned their facility-level exposure. Intervention DPO versus EPO. Outcomes All-cause mortality, cardiovascular mortality; composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Measurements Unadjusted and adjusted HRs from Cox proportional hazards regression models. Results Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (versus EPO) was 1.06 (95% CI, 1.00–1.13) and remained materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99–1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94–1.16). Non-fatal outcomes were evaluated among 9455 patients with fee-for-service Medicare: 4542 (48.0%) in DPO and 4913 (52.0%) in EPO facilities. Over 10,427 and 10,335 person-years, 246 strokes and 370 MIs were recorded, respectively. We found no differences in adjusted stroke or MI rates, or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96–1

  4. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

    PubMed Central

    Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

    2016-01-01

    Objective Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. Material and Methods In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient’s baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. Results The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years [“for the long- and antagonist-protocol groups, respectively”]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Conclusion Our results show that ART cycles could be

  5. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

    PubMed Central

    Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

    2016-01-01

    Objective Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. Material and Methods In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient’s baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. Results The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years [“for the long- and antagonist-protocol groups, respectively”]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Conclusion Our results show that ART cycles could be

  6. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  7. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods.

    PubMed

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Wilkinson, A G; Macnaught, Gillian; Semple, Scott I; Boardman, James P

    2016-01-01

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course. PMID:27010238

  8. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods

    PubMed Central

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Wilkinson, A. G.; Macnaught, Gillian; Semple, Scott I.; Boardman, James P.

    2016-01-01

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases ‘uniformly’ distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course. PMID:27010238

  9. Prophylactic recombinant epoetin alfa markedly reduces the need for blood transfusion in patients with metastatic melanoma treated with biochemotherapy.

    PubMed

    Wolchok, J D; Klimek, V M; Williams, L; Chapman, P B

    1999-12-01

    Treatment of metastatic melanoma with biochemotherapy results in the rapid onset of anemia, requiring blood transfusion in 9 of 13 (69%) patients. Prophylactic use of weekly subcutaneous recombinant epoetin alfa eliminated the need for transfusion in all but 1 of 21 (5%) patients.

  10. Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.

    PubMed

    Ahmadian, Haleh; Hansen, Ernst B; Faber, Johan H; Sejergaard, Lars; Karlsson, Johan; Bolt, Gert; Hansen, Jens J; Thim, Lars

    2016-07-01

    Turoctocog alfa (NovoEight) is a third-generation recombinant factor VIII (rFVIII) with a truncated B-domain that is manufactured in Chinese hamster ovary cells. No human or animal-derived materials are used in the process. The aim of this study is to describe the molecular design and purification process for turoctocog alfa. A five-step purification process is applied to turoctocog alfa: protein capture on mixed-mode resin; immunoaffinity chromatography using a unique, recombinantly produced anti-FVIII mAb; anion exchange chromatography; nanofiltration and size exclusion chromatography. This process enabled reduction of impurities such as host cell proteins (HCPs) and high molecular weight proteins (HMWPs) to a very low level. The immunoaffinity step is very important for the removal of FVIII-related degradation products. Manufacturing scale data shown in this article confirmed the robustness of the purification process and a reliable and consistent reduction of the impurities. The contribution of each step to the final product purity is described and shown for three manufacturing batches. Turoctocog alfa, a third-generation B-domain truncated rFVIII product is manufactured in Chinese hamster ovary cells without the use of animal or human-derived proteins. The five-step purification process results in a homogenous, highly purified rFVIII product.

  11. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    PubMed Central

    Monroe, Dougald M.; Jenny, Richard J.; Van Cott, Kevin E.; Saward, Laura L.

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  12. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods

    NASA Astrophysics Data System (ADS)

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Wilkinson, A. G.; MacNaught, Gillian; Semple, Scott I.; Boardman, James P.

    2016-03-01

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases ‘uniformly’ distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

  13. An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease

    PubMed Central

    Hollak, Carla EM

    2012-01-01

    Gaucher disease is an inherited lysosomal storage disorder, characterized by deficient activity of glucocerebrosidase leading to storage of glucocerebroside in tissue macrophages. Type I disease, the most prevalent form, lacks central nervous system involvement but presents primarily with variable degrees of hepatosplenomegaly, cytopenia, and bone disease. Intravenous enzyme replacement therapy can reverse these manifestations. In addition to the two enzymes currently authorized for use, the newest enzyme, taliglucerase alfa, is at the late stages of clinical development. Taliglucerase alfa is a unique product, as it is the first plant cell–based recombinant enzyme therapy. This review considers the existing evidence for therapeutic efficacy of taliglucerase alfa in the treatment of the non-neuronopathic manifestations of Gaucher disease. Clinical studies encompass one phase I trial in healthy volunteers, one phase III trial, and preliminary results from both an extension study and a switch study. In the 9-month, randomized, double-blind phase III trial, treatment-naïve patients with type I Gaucher disease were treated with either 30 or 60 U/kg every 2 weeks. Dose-dependent improvements were achieved after 6 and 9 months of therapy, with reductions in spleen and liver volumes and improvements in hemoglobin levels. Platelet counts improved initially only in the higher-dose group, but preliminary results from the extension study also show significant increases in the lower-dose group. Bone marrow involvement, as assessed by magnetic resonance imaging, improved in almost all patients. Taliglucerase alfa has shown a good safety profile, with few patients experiencing hypersensitivity reactions and developing antibodies. An additional enzyme replacement therapy for Gaucher disease would enable the treatment of more patients and would provide backup for unexpected production problems. Furthermore, it is expected that this new treatment would reduce the costs of

  14. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

    PubMed Central

    Norman, Robert J.; Zegers-Hochschild, Fernando; Salle, Bruno S.; Elbers, Jolanda; Heijnen, Esther; Marintcheva-Petrova, Maya; Mannaerts, Bernadette

    2011-01-01

    BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity. The trial was registered under ClinicalTrials.gov identifier NCT00696878. PMID:21622693

  15. A Randomized Controlled Study of Weekly and Biweekly Dosing of Epoetin Alfa in CKD Patients With Anemia

    PubMed Central

    Gartenberg, Gary; Fu, Min; Wolfson, Marsha; Rao, Sudhakar; Bowers, Peter

    2009-01-01

    Background and objectives: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing. Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl. Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients. Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects. PMID:19808215

  16. Recombinant interferon alfa-2a, an active agent in advanced cutaneous T-cell lymphomas.

    PubMed

    Bunn, P A; Ihde, D C; Foon, K A

    1987-01-01

    The cutaneous T-cell lymphomas including mycosis fungoides and the Sézary syndrome, are indolent lymphomas with early systemic dissemination. Like the indolent B-cell lymphomas, they cannot be cured by currently available systemic chemotherapy so new systemic therapies need to be developed. A study of very high-dose recombinant interferon alfa-2a was, therefore, initiated in 20 patients with advanced cutaneous T-cell lymphoma (5 in stage II, 2 in stage III and 13 in stage IV). All patients were refractory to at least 2 standard therapies, including topical nitrogen mustard (18 patients), psoralens and ultraviolet A light (12 patients), total skin electron irradiation (14 patients) and systemic chemotherapy (16 patients). Nine out of 20 patients (45%; 95% confidence interval 25-69%) had either objective partial or complete responses within 3 months of starting treatment. Maximal response, however, often did not occur for at least one year. The median duration of response was 5.5 months and all complete responses lasted more than 2 years. Response frequencies were equal at both cutaneous and extracutaneous sites and in patients with or without prior chemotherapy. Toxicity was exhibited primarily as a flu-like syndrome consisting of fever, malaise, fatigue, anorexia and weight loss which necessitated dose reductions in all patients. Transient elevations in liver function and decreases in renal function and granulocyte counts occurred in some patients. It is concluded that interferon alfa-2a is highly active against advanced cutaneous T-cell lymphomas and that it should be studied in its early stages. It should also be evaluated in combination with other biological agents and with chemotherapy.

  17. Home treatment of attacks with conestat alfa in hereditary angioedema due to C1-inhibitor deficiency.

    PubMed

    Farkas, Henriette; Csuka, Dorottya; Veszeli, Nóra; Zotter, Zsuzsanna; Szabó, Erika; Varga, Lilian

    2014-01-01

    Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the acute treatment of hereditary angioedema due to C1-INH (HAE-C1-INH) deficiency. Our aim was to investigate the efficacy and safety profile of conestat alfa in patients with HAE-C1-INH, under real-life conditions. We analyzed 65 edematous episodes requiring acute treatment and occurring in two female HAE-C1-INH patients. The patients were treated at home with rhC1-INH per occasion. They recorded the time of rhC1-INH administration, the time to the onset of improvement, and time to the complete resolution of symptoms, as well as the side effects. Symptom severity and patient satisfaction were measured with a visual analog scale (VAS). Thirty-three HAE attacks occurred in submucosal tissue, 17 in subcutaneous tissue, and 15 had mixed locations. After the administration of rhC1-INH, clinical symptoms improved within 0.50 (0.17-4.50 hours) hours and resolved completely within 9.00 (1.67-58.75 hours) hours. The time between the onset of the attack and the administration of rhC1-INH was correlated with the time when the symptoms stopped worsening (R = 0.3212; p = 0.0096) and the time to complete resolution of the symptoms (R = 0.4774; p < 0.0001). The time to response to the drug differed with attack location. The efficacy and safety of rhC1-INH persisted after repeated use. None of the patients experienced a recurrence of the HAE attack or drug-related systemic adverse events. The mean VAS score of patient satisfaction was 93.14. Home treatment with rhC1-INH was an effective and well-tolerated therapy for all types of HAE attacks.

  18. Durability of responses to interferon alfa-2b in advanced hairy cell leukemia.

    PubMed

    Ratain, M J; Golomb, H M; Bardawil, R G; Vardiman, J W; Westbrook, C A; Kaminer, L S; Lembersky, B C; Bitter, M A; Daly, K

    1987-03-01

    Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow. PMID:3814819

  19. A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C

    PubMed Central

    Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

    2016-01-01

    Background A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Methods Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. Results A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. Conclusions In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment

  20. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

    PubMed Central

    Carrera, Fernando; Lok, Charmaine E.; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F.E.; Canaud, Bernard; Kerr, Peter G.; Macdougall, Iain C.; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C.

    2010-01-01

    Background. Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. Methods. Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11–13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50–53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. Results. Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. Conclusions. Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa

  1. [Experience of use of allokin-alfa in the treatment of genitourinary infections complicated by excretory-toxic infertility].

    PubMed

    Akimov, O V; Kostromeev, S A; Dyshkovets, A A

    2013-01-01

    The results of the examination and treatment of 67 patients aged 18 to 45 years are presented. Patients suffered from chronic prostatitis, chronic prostatovesiculitis, chronic uretroprostatitis complicated by excretory-toxic infertility. Pathogens, including sexually transmitted infections (STIs), were identified in all patients. The control group received conventional therapy (causative agents, a-adrenoblockers, enzyme therapy). In the study group, patients received allokin alpha in addition to conventional therapy. The use of allokin-alfa promoted more rapid and complete eradication of STI pathogens, and normalization of the spermogram. The results of this study allow to recommend allokin-alfa for the combined treatment of patients with infectious and inflammatory diseases of the genitourinary system, complicated by excretory-toxic infertility.

  2. Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease.

    PubMed

    Elstein, Deborah; Mehta, Atul; Hughes, Derralynn A; Giraldo, Pilar; Charrow, Joel; Smith, Laurie; Shankar, Suma P; Hangartner, Thomas N; Kunes, Yune; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-07-01

    Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 × 10(9) /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for anti-imiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes. PMID:25776130

  3. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid.

    PubMed

    Wilber, Randall L

    2002-01-01

    The use of DNA-recombinant human epoetin-alfa (rhEPO) as a pharmacological ergogenic aid for the enhancement of aerobic performance is estimated to be practised by at least 3 to 7% of elite endurance sport athletes. rhEPO is synthesised from Chinese hamster ovary cells, and is nearly identical biochemically and immunologically to endogenous epoetin-alfa (EPO). In a clinical setting, rhEPO is used to stimulate erythrocyte production in patients with end-stage renal disease and anaemia. A limited number of human studies have suggested that rhEPO provides a significant erythropoietic and ergogenic benefit in trained individuals as evidenced by increments in haemoglobin, haematocrit, maximal oxygen uptake (VO2max) and exercise endurance time. The purpose of this review is to summarise the various technologies and methodologies currently available for the detection of illicit use of rhEPO in athletes. The International Olympic Committee (IOC) banned the use of rhEPO as an ergogenic aid in 1990. Since then a number of methods have been proposed as potential techniques for detecting the illegal use of rhEPO. Most of these techniques use indirect markers to detect rhEPO in blood samples. These indirect markers include macrocytic hypochromatic erythrocytes and serum soluble transferrin receptor (sTfr) concentration. Another indirect technique uses a combination of 5 markers of enhanced erythropoiesis (haematocrit, reticulocyte haematocrit, percentage of macrocytic red blood cells, serum EPO, sTfr) to detect rhEPO. The electrophoretic mobility technique provides a direct measurement of urine and serum levels of rhEPO, and is based on the principle that the rhEPO molecule is less negatively charged versus the endogenous EPO molecule. Isoelectric patterning/focusing has emerged recently as a potential method for the direct analysis of rhEPO in urine. Among these various methodologies, the indirect technique that utilises multiple markers of enhanced erythropoiesis appears to

  4. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid.

    PubMed

    Wilber, Randall L

    2002-01-01

    The use of DNA-recombinant human epoetin-alfa (rhEPO) as a pharmacological ergogenic aid for the enhancement of aerobic performance is estimated to be practised by at least 3 to 7% of elite endurance sport athletes. rhEPO is synthesised from Chinese hamster ovary cells, and is nearly identical biochemically and immunologically to endogenous epoetin-alfa (EPO). In a clinical setting, rhEPO is used to stimulate erythrocyte production in patients with end-stage renal disease and anaemia. A limited number of human studies have suggested that rhEPO provides a significant erythropoietic and ergogenic benefit in trained individuals as evidenced by increments in haemoglobin, haematocrit, maximal oxygen uptake (VO2max) and exercise endurance time. The purpose of this review is to summarise the various technologies and methodologies currently available for the detection of illicit use of rhEPO in athletes. The International Olympic Committee (IOC) banned the use of rhEPO as an ergogenic aid in 1990. Since then a number of methods have been proposed as potential techniques for detecting the illegal use of rhEPO. Most of these techniques use indirect markers to detect rhEPO in blood samples. These indirect markers include macrocytic hypochromatic erythrocytes and serum soluble transferrin receptor (sTfr) concentration. Another indirect technique uses a combination of 5 markers of enhanced erythropoiesis (haematocrit, reticulocyte haematocrit, percentage of macrocytic red blood cells, serum EPO, sTfr) to detect rhEPO. The electrophoretic mobility technique provides a direct measurement of urine and serum levels of rhEPO, and is based on the principle that the rhEPO molecule is less negatively charged versus the endogenous EPO molecule. Isoelectric patterning/focusing has emerged recently as a potential method for the direct analysis of rhEPO in urine. Among these various methodologies, the indirect technique that utilises multiple markers of enhanced erythropoiesis appears to

  5. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma

  7. Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease

    PubMed Central

    Abbas, Richat; Park, Glen; Damle, Bharat; Chertkoff, Raul; Alon, Sari

    2015-01-01

    Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy approved in the United States, Israel, and other countries for treatment of Type 1 Gaucher disease in adults, and is the first approved plant cell—expressed recombinant protein. In this report, taliglucerase alfa pharmacokinetics were assessed in adult and pediatric patients with Gaucher disease from separate multicenter trials of 30 Units/kg and 60 Units/kg doses infused every 2 weeks. Serial blood samples were obtained from adult patients following single-dose administration on day 1 (n = 26) and multiple doses at week 38 (n = 29), and from pediatric patients following administration of multiple doses of taliglucerase alfa for 10–27 months (n = 10). In both adult and pediatric patients, maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to last measureable concentration (AUC0-t), and from time zero to infinity (AUC0-∞) were higher after 60 Units/kg dose than 30 Units/kg dose. No tendency for accumulation or change in taliglucerase alfa pharmacokinetic parameters over time from day 1 to week 38 was observed with repeated doses of 30 or 60 Units/kg in adults. After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5–95.4) in adults and 46.6 (34.4–68.4) in pediatric patients, AUC0 t expressed in ng•h/mL/mg was 63.4 (26.3–156) in adults and 63.9 (39.8–85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3–104) in adults and 31.5 (18.0–42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25–37.9) in adults and 17.0 (11.7–24.9) in pediatric patients. These pharmacokinetic data extend the findings of taliglucerase alfa in adult and pediatric patients. Trial Registration ClinicalTrials.gov. NCT00376168 (in adults); NCT01411228 (in children) PMID

  8. Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

    PubMed Central

    Hu, Tiffany Y; Vaidya, Vaibhav R; Asirvatham, Samuel J

    2016-01-01

    Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials. PMID:26937198

  9. Cholangiolocellular carcinoma with rapid progression initially showing abnormally elevated serum alfa-fetoprotein.

    PubMed

    Yoh, Tomoaki; Kato, Tatsushi; Hirohata, Yoshiaki; Nakamura, Yuya; Nakayama, Hiroyuki; Okamura, Ryuji

    2016-08-01

    Cholangiolocellular carcinoma (CoCC) is a rare malignant liver tumor derived from hepatic progenitor cells, which exist in the canals of Hering. We encountered a case of CoCC with an extremely poor clinical course, initially showing abnormally elevated serum alfa-fetoprotein (AFP). A 72-year-old male presented with a liver tumor and abnormally elevated serum AFP levels (16,399 ng/ml). We preoperatively diagnosed hepatocellular carcinoma and performed extended right hepatectomy, after which the serum AFP levels remarkably decreased to 97 ng/ml. Postoperatively, the disease was pathologically diagnosed as CoCC. Furthermore, immunohistochemical pathological findings were alcian blue negative, cytokeratin (CK) 7 partially positive, CK19 positive, hepatocyte paraffin-1 negative, membranous negative for epithelial membrane antigen, and AFP negative. Fifty-five days later, intra- and extrahepatic recurrence developed, and the patient died 65 days after surgery. Although CoCCs show favorable outcomes, these characteristics of our case were not previously reported. It is necessary to accumulate more information on CoCC. PMID:27363839

  10. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; García, E L; Talavera, A; Guzmán, R

    1992-11-01

    Forty-eight consecutive patients with diffuse large cell lymphoma (DLCL) in complete remission (CR) after conventional chemotherapy were enrolled in a prospective clinical trial. The maintenance therapy was a random either nothing or interferon alfa 2b (IFN) 5.0 MU three times a week for one year. The median duration of CR in the patients treated with IFN has not been reached. After five years 60% of patients remain in CR compared to the control group who had a median CR of 40 months (p < 0.001). Actuarial five-years survival in the IFN treated patients was 88% compared to 42% in the control group (p < 0.001). Maintenance therapy with IFN has been beneficial in patients with DLCL with improvement of duration of CR and survival without the excessive toxicity of most common third generation regimen chemotherapy. We felt that IFN could be explored in most controlled clinical trials in patients with DLCL in CR after conventional chemotherapy. PMID:1487412

  11. [Switch of methoxy-polyethylene-glycol-epoetin beta to darbepoetin alfa in 263 dialysis patients].

    PubMed

    Rieger, J; Krummel, T; Petitjean, P; Chantrel, F; Dimitrov, Y

    2016-01-01

    In early 2012, due to national supply disruption, the methoxy-polyethylene glycol-epoetin beta (CERA) was no longer available and has been replaced by darbepoetin alfa (DA) in all dialysis patients. Official recommendations for the replacement of one by the other is missing or unclear. On this occasion, we wanted to examine how the shift from CERA to DA was done in terms of dose conversion factor and the other factors that could have influenced the dose of DA prescribed (hemoglobin, patient weight, dose of CERA). This retrospective multicenter open conducted in six dialysis centers in Alsace is the first large study (n=263) that evaluated the switch from CERA to DA in all chronic hemodialysis patients. We found that the instantaneous ratio of dose adjustment is close to 1 and that nephrologists are mainly based on the dose of CERA for determining the DA dose, before hemoglobin and weight. However, establishing a true dose-response ratio between the two molecules requires a long term prospective study.

  12. Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Shankar, Suma P; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Amato, Dominick J; Szer, Jeffrey; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2016-07-01

    Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc. PMID:27102949

  13. Pharmacokinetic and Pharmacodynamic Profiles of Extended Dosing of Epoetin Alfa in Anemic Patients Who Have Chronic Kidney Disease and Are Not on Dialysis

    PubMed Central

    McGowan, Tracy; Vaccaro, Nicole M.; Beaver, Jessica S.; Massarella, Joseph; Wolfson, Marsha

    2008-01-01

    Background and objectives: Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis. Design, setting, participants, & measurements: Thirty-eight patients, enrolled from nine centers in the United States, were ≥18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m2. Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted. Results: Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related. Conclusions: Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis. PMID:18417741

  14. Epoetin alfa. A review of its clinical efficacy in the management of anaemia associated with renal failure and chronic disease and its use in surgical patients.

    PubMed

    Dunn, C J; Wagstaff, A J

    1995-08-01

    Epoetin alfa is a recombinant form of erythropoietin, a glycoprotein hormone which stimulates red blood cell production by stimulating the activity of erythroid progenitor cells. This review discusses the use of the drug in the management of anaemia in diseases often associated with advancing age [renal failure, cancer, rheumatoid arthritis (RA) and other chronic diseases, and the myelodysplastic syndromes (MDS)] and in surgical patients. Intravenous and subcutaneous therapy with epoetin alfa raises haematocrit and haemoglobin levels, and reduces transfusion requirements, in anaemic patients with end-stage renal failure undergoing haemodialysis or peritoneal dialysis. The drug is also effective in the correction of anaemia in patients with chronic renal failure not yet requiring dialysis and does not appear to affect renal haemodynamics adversely or to precipitate the onset of end-stage renal failure. Response rates of 32 to 82% with epoetin alfa therapy have been reported in patients with anaemia associated with cancer or cytotoxic chemotherapy. Limited data in patients with anaemia associated with RA show correction of anaemia after epoetin alfa treatment. Response rates to the drug of 0 to 56% have been noted in patients with MDS. Epoetin alfa also reduces anaemia, increases the capacity for autologous blood donation and reduces the need for allogeneic blood transfusion in patients scheduled to undergo surgery. Hypertension occurs in 30 to 35% of patients with end-stage renal failure who receive epoetin alfa, but this can be managed successfully with correction of fluid status and antihypertensive medication where necessary, and is minimised by avoiding rapid increases in haematocrit. Although vascular access thrombosis has not been conclusively linked to therapy with the drug, increased heparinisation may be required when it is administered to patients on haemodialysis. Epoetin alfa does not appear to exert any direct cerebrovascular adverse effects. Thus

  15. Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study

    PubMed Central

    2010-01-01

    Background Self-administration of recombinant human follicle-stimulating hormone (r-hFSH) can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany. Methods This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device. Results A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p < 0.001 'less' versus 'more' training). Significantly more patients rated the prefilled follitropin alfa pen as easier in terms of use (2321/3206, 72.4%; p < 0.001 'much more easy' versus 'less easy') and daily injection (2384/3262, 73.1%; p < 0.001 'much more easy' versus 'less easy') than existing injection methods. Approximately one third of respondents rated the prefilled follitropin alfa pen as easier to use than the follitropin beta pen with reloadable cartridges. The majority (3378/4024, 83.9%) of patients had a general preference for the prefilled follitropin alfa pen over other injection methods. Conclusions In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins

  16. Direct site-specific glycoform identification and quantitative comparison of glycoprotein therapeutics: imiglucerase and velaglucerase alfa.

    PubMed

    Ye, Hongping; Hill, John; Gucinski, Ashley C; Boyne, Michael T; Buhse, Lucinda F

    2015-03-01

    Gaucher disease, the most common lysosomal metabolic disorder, can be treated with enzyme replacement therapy (ERT). Recombinant human glucocerebrosidase imiglucerase (Cerezyme(®)), produced in Chinese hamster ovary cells, has been used for ERT of Gaucher disease for 20 years. Another recombinant glucocerebrosidase velaglucerase alfa (VPRIV), expressed in a human fibroblast cell line, was approved by the US Food and Drug Administration in 2010. The amino acid sequence difference at residue 495 of these two products is well documented. The overall N-linked qualitative glycan composition of these two products has also been reported previously. Herein, employing our recently developed approach utilizing isobaric tandem mass tag (TMT) labeling and an LTQ Orbitrap XL electron transfer dissociation (ETD) hybrid mass spectrometer, the site-specific glycoforms of these products were identified with ETD and collision-induced dissociation (CID) spectra. The quantitative comparison of site-specific glycans was achieved utilizing higher-energy collisional dissociation (HCD) spectra with a NanoMate used as both a fraction collector and a sample introduction device. From the trypsin-digested mixture of these two products, over 90 glycopeptides were identified by accurate mass matching. In addition to those previously reported, additional glycopeptides were detected with moderate abundance. The relative amount of each glycoform at a specific glycosylation site was determined based on reporter signal intensities of the TMT labeling reagents. This is the first report of site-specific simultaneous qualitative and quantitative comparison of glycoforms for Cerezyme(®) and VPRIV. The results demonstrate that this method could be utilized for biosimilarity determination and counterfeit identification of glycoproteins. PMID:25501675

  17. Peginesatide for Maintenance Treatment of Anemia in Hemodialysis and Nondialysis Patients Previously Treated with Darbepoetin Alfa

    PubMed Central

    Roger, Simon D.; Martin, Edouard; Runyan, Grant; O’Neil, Janet; Qiu, Ping; Locatelli, Francesco

    2013-01-01

    Summary Background and objectives Peginesatide (Omontys) is a novel, synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent (ESA) that is designed to specifically stimulate the erythropoietin receptor. This study evaluated maintenance of hemoglobin levels in patients after conversion from darbepoetin alfa to once-monthly peginesatide. Design, setting, participants, & measurements This open-label, multicenter study included 101 CKD patients, 52 of whom were receiving dialysis. The duration of the study was 24 weeks. The primary endpoint was the mean change in hemoglobin from baseline to the evaluation period (weeks 19–24). The study was conducted during the period from September 22, 2008 to December 24, 2009. Results The mean change among hemodialysis patients was –0.42 g/dl (95% confidence interval, –0.65 to –0.19) and the mean change among CKD nondialysis patients was 0.49 g/dl (95% confidence interval, 0.26–0.71). The percentages of patients who maintained hemoglobin levels within ±1.0 g/dl of baseline values were as follows: 80.0% for hemodialysis and 68.1% for nondialysis, and73.3% for hemodialysis and 68.1% for nondialysis within the target range of 10.0–12.0 g/dl. Few patients received red blood cell transfusions (hemodialysis, 5.8%; nondialysis, 2.0%). Seventy-nine patients experienced adverse events, the majority of which were mild or moderate in severity. There were 40 serious adverse events and 2 deaths reported. Conclusions In this study, once-monthly peginesatide resulted in a slight decrease in mean hemoglobin levels in individuals on hemodialysis and a small increase in individuals with CKD who were not on dialysis. PMID:23243269

  18. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  19. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y

    PubMed Central

    Jones, Simon A.; Bialer, Martin; Parini, Rossella; Martin, Ken; Wang, Hui; Yang, Ke; Shaywitz, Adam J.; Harmatz, Paul

    2015-01-01

    Background: Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged ≥5 y. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients. Methods: Fifteen Morquio A patients aged <5 y received elosulfase alfa 2.0 mg/kg/week for 52 wk during the primary treatment phase of a phase II, open-label, multinational study. Primary endpoint was safety and tolerability; secondary endpoints were change in uKS and growth velocity over 52 wk. Results: All 15 patients completed the primary treatment phase. Six of 743 infusions (0.8%) administered led to adverse events (AEs) requiring infusion interruption and medical intervention. Eleven patients (73.3%) had ≥1 study drug-related AE, mostly infusion-associated reactions. Mean z-score growth rate per year numerically improved from −0.6 at baseline to −0.4 at week 52. Comparison to untreated subjects of similar age in the Morquio A Clinical Assessment Program study showed a smaller decrease in height z-scores for treated than for untreated patients. Mean percent change from baseline in uKS was −30.2% at 2 wk and −43.5% at 52 wk. Conclusion: Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth. PMID:26331768

  20. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency.

    PubMed

    Thurberg, Beth L; Wasserstein, Melissa P; Jones, Simon A; Schiano, Thomas D; Cox, Gerald F; Puga, Ana Cristina

    2016-09-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  1. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Schiano, Thomas D.; Cox, Gerald F.; Puga, Ana Cristina

    2016-01-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  2. Mapping Hydrogen in the Galaxy, Galactic Halo, and Local Group with ALFA: The GALFA-H I Survey Starting with TOGS

    NASA Astrophysics Data System (ADS)

    Gibson, S. J.; Douglas, K. A.; Heiles, C.; Korpela, E. J.; Peek, J. E. G.; Putman, M. E.; Stanimirović, S.

    2008-08-01

    Radio observations of gas in the Milky Way and Local Group are vital for understanding how galaxies function as systems. The unique sensitivity of Arecibo's 305 m dish, coupled with the 7-beam Arecibo L-Band Feed Array (ALFA), provides an unparalleled tool for investigating the full range of interstellar phenomena traced by the H I 21 cm line. The GALFA (Galactic ALFA) H I Survey is mapping the entire Arecibo sky over a velocity range of -700 to +700 km s-1 with 0.2 km s-1 velocity channels and an angular resolution of 3.4'. We present highlights from the TOGS (Turn On GALFA Survey) portion of GALFA-H I, which is covering thousands of square degrees in commensal drift scan observations with the ALFALFA and AGES extragalactic ALFA surveys. This work is supported in part by the National Astronomy and Ionosphere Center, operated by Cornell University under cooperative agreement with the National Science Foundation.

  3. [Alfa-blockade with doxazosin vs tamsulozin in combination of intermittent androgen blockade in patients with prostate cancer].

    PubMed

    Muradian, A A

    2005-03-01

    We have studied the efficacy of Alfa-blockade with Doxazosin vs Tamsulozin in combination with Intermittent Androgen Blockade (IAB) in patients with low grade prostate cancer. Our clinical trial included: I group (n=15) of patients who received doxazosin with IAB and flutamide; II group (n=13) of patients who received tamsulozin in combination with IAB and flutamide and III (n=33) group with flutamid monotherapy alone. Our results have shown that the combination of doxasozin and IAB with the flutamide leads to the better improvement of uroflowmetry and IPSS parameters, whereas the tamsulozin and IAB with flutamide combination induce those improvements for the longer period during the disease remission.

  4. Antibody-mediated pure red cell aplasia (PRCA) on switching from darbepoetin alfa to epoetin beta: what are the implications?

    PubMed Central

    Assunção, José; Vinhas, José

    2008-01-01

    We report the development of antibody-mediated pure red cell aplasia (PRCA) in a 63-year-old man with end-stage renal disease following a switch from darbepoetin alfa to epoetin beta. Haemoglobin levels began to decrease 6 months after the switch. Increasing the epoetin beta dose produced no response and regular blood transfusions were required; PRCA was confirmed and epoetin beta was discontinued. The patient responded positively to immunosuppression; after 2 months on prednisone and cyclophosphamide, haemoglobin levels stabilized and no further transfusions were required. This case highlights the difficulty in establishing a cause-effect relationship where more than one erythropoiesis-stimulating agent is involved. PMID:25983889

  5. Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction

    PubMed Central

    Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin

    2015-01-01

    Objective To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Methods Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. Results There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Conclusion Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS. PMID:26161335

  6. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  8. Vibrational distributions of AlF(a /sup 3/Pi) produced by crossed-beam collisions of Al and F/sub 2/ at two kinetic energies

    SciTech Connect

    Ishikawa, T.; Parson, J.M.

    1983-11-01

    Chemiluminescent spectra of AlF(a /sup 3/Pi) produced in the reaction of Al with an F/sub 2/ nozzle beam are reported at two different nozzle temperatures. From spectral simulations treating AlF(a /sup 3/Pi) in the intermediate case between Hund's cases (a) and (b), it is found that the peak position of the derived vibrational distribution is shifted to a higher vibrational state for the higher temperature case. Both vibrational distributions give linear surprisal plots with nearly the same highly negative slope. In order to explain the shift of the vibrational distribution, a collinear model calculation for multiple nonadiabatic processes is proposed.

  9. The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa.

    PubMed

    Baek, Rena C; Palmer, Rachel; Pomponio, Robert J; Lu, Yuefeng; Ma, Xiwen; McVie-Wylie, Alison J

    2016-09-01

    Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation. PMID:27489778

  10. Population Pharmacokinetic and Pharmacodynamic Model-Based Comparability Assessment of a Recombinant Human Epoetin Alfa and the Biosimilar HX575

    PubMed Central

    Yan, Xiaoyu; Lowe, Philip J.; Fink, Martin; Berghout, Alexander; Balser, Sigrid; Krzyzanski, Wojciech

    2012-01-01

    The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic (PK/PD) model and assess the comparability between epoetin alfa HEXAL/Binocrit (HX575) and a comparator epoetin alfa by a model-based approach. PK/PD data—including serum drug concentrations, reticulocyte counts, red blood cells, and hemoglobin levels—were obtained from 2 clinical studies. In sum, 149 healthy men received multiple intravenous or subcutaneous doses of HX575 (100 IU/kg) and the comparator 3 times a week for 4 weeks. A population model based on pharmacodynamics-mediated drug disposition and cell maturation processes was used to characterize the PK/PD data for the 2 drugs. Simulations showed that due to target amount changes, total clearance may increase up to 2.4-fold as compared with the baseline. Further simulations suggested that once-weekly and thrice-weekly subcutaneous dosing regimens would result in similar efficacy. The findings from the model-based analysis were consistent with previous results using the standard noncompartmental approach demonstrating PK/PD comparability between HX575 and comparator. However, due to complexity of the PK/PD model, control of random effects was not straightforward. Whereas population PK/PD model-based analyses are suited for studying complex biological systems, such models have their limitations (statistical), and their comparability results should be interpreted carefully. PMID:22162538

  11. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

    PubMed Central

    McMurray, John J.V.; Anand, Inder S.; Diaz, Rafael; Maggioni, Aldo P.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Tendera, Michal; van Veldhuisen, Dirk J.; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B.; Amuchastegui, M.; Belziti, C.; Bluguermann, J.; Caccavo, M.; Cartasegna, L.; Colque, R.; Cuneo, C.; Fernandez, A.; Gabito, A.; Goicochea, R.; Gonzalez, M.; Gorosito, V.; Grinfeld, L.; Hominal, M.; Kevorkian, R.; Litvak Bruno, M.; Llanos, J.; Mackinnon, I.; Manuale, O.; Marzetti, E.; Nul, D.; Perna, E.; Riccitelli, M.; Sanchez, A.; Santos, D.; Schygiel, P.; Toblli, J.; Vogel, D.; Aggarwal, A.; Amerena, J.; De Looze, F.; Fletcher, P.; Hare, D.; Ireland, M.; Krum, H.; Lattimore, J.; Marwick, T.; Sindone, A.; Thompson, P.; Waites, J.; Altenberger, J.; Ebner, C.; Lenz, K.; Pacher, R.; Poelzl, G.; Charlier, F.; de Ceuninck, M.; De Keulenaer, G.; Dendale, P.; Maréchal, P.; Mullens, W.; Thoeng, J.; Vanderheyden, M.; Vanhaecke, J.; Weytjens, C.; Wollaert, B.; Albuquerque, D.; Almeida, D.; Aspe y Rosas, J.; Bocchi, E.; Bordignon, S.; Clausell, N.; Kaiser, S.; Leaes, P.; Martins Alves, S.; Montera, M.; Moura, L.; Pereira de Castro, R.; Rassi, S.; Reis, A.; Saraiva, J.; Simões, M.; Souza Neto, J.; Teixeira, M.; Benov, H.; Chompalova, B.; Donova, T.; Georgiev, P.; Gotchev, D.; Goudev, A.; Grigorov, M.; Guenova, D.; Hergeldjieva, V.; Ivanov, D.; Kostova, E.; Manolova, A.; Marchev, S.; Nikolov, F.; Popov, A.; Raev, D.; Tzekova, M.; Czarnecki, W.; Giannetti, N.; Haddad, H.; Heath, J.; Huynh, T.; Lepage, S.; Liu, P.; Lonn, E.; Ma, P.; Manyari, D.; Moe, G.; Parker, J.; Pesant, Y.; Rajda, M.; Ricci, J.; Roth, S.; Sestier, F.; Sluzar, V.; Sussex, B.; Vizel, S.; Antezana, G.; Bugueno, C.; Castro, P.; Conejeros, C.; Manriquez, L.; Martinez, D.; Potthoff, S.; Stockins, B.; Vukasovic, J.; Gregor, P.; Herold, M.; Jerabek, O.; Jirmar, R.; Kuchar, R.; Linhart, A.; Podzemska, B.; Soucek, M.; Spac, J.; Spacek, R.; Vodnansky, P.; Bronnum-Schou, J.; Clemmensen, K.; Egstrup, K.; Jensen, G.; Kjoller-Hansen, L.; Kober, L.; Markenvard, J.; Rokkedal, J.; Skagen, K.; Torp-Pedersen, C.; Tuxen, C.; Videbak, L.; Laks, T.; Vahula, V.; Harjola, V.; Kettunen, R.; Kotila, M.; Bauer, F.; Cohen Solal, A.; Coisne, D.; Davy, J.; De Groote, P.; Dos Santos, P.; Funck, F.; Galinier, M.; Gibelin, P.; Isnard, R.; Neuder, Y.; Roul, G.; Sabatier, R.; Trochu, J.; Anker, S.; Denny, S.; Dreykluft, T.; Flesch, M.; Genth-Zotz, S.; Hambrecht, R.; Hein, J.; Jeserich, M.; John, M.; Kreider-Stempfle, H.; Laufs, U.; Muellerleile, K.; Natour, M.; Sandri, M.; Schäufele, T.; von Hodenberg, E.; Weyland, K.; Winkelmann, B.; Tse, H.; Yan, B.; Barsi, B.; Csikasz, J.; Dezsi, C.; Edes, I.; Forster, T.; Karpati, P.; Kerekes, C.; Kis, E.; Kosa, I.; Lupkovics, G.; Nagy, A.; Preda, I.; Ronaszeki, A.; Tomcsanyi, J.; Zamolyi, K.; Agarwal, D.; Bahl, V.; Bordoloi, A.; Chockalingam, K.; Chopda, M.; Chopra, V.; Dugal, J.; Ghaisas, N.; Ghosh, S.; Grant, P.; Hiremath, S.; Iyengar, S.; Jagadeesa Subramania, B.; Jain, P.; Joshi, A.; Khan, A.; Mullasari, A.; Naik, S.; Oomman, A.; Pai, V.; Pareppally Gopal, R.; Parikh, K.; Patel, T.; Prakash, V.; Sastry, B.; Sathe, S.; Sinha, N.; Srikanthan, V.; Subburamakrishnan, P.; Thacker, H.; Wander, G.; Admon, D.; Katz, A.; Klainman, E.; Lewis, B.; Marmor, A.; Moriel, M.; Mosseri, M.; Shotan, A.; Weinstein, J.; Zimlichman, R.; Agostoni, P.; Albanese, M.; Alunni, G.; Bini, R.; Boccanelli, A.; Bolognese, L.; Campana, C.; Carbonieri, E.; Carpino, C.; Checco, L.; Cosmi, F.; D'Angelo, G.; De Cristofaro, M.; Floresta, A.; Fucili, A.; Galvani, M.; Ivleva, A.; Marra, S.; Musca, G.; Peccerillo, N.; Perrone Filardi, P.; Picchio, E.; Russo, T.; Scelsi, L.; Senni, M.; Tavazzi, L.; Erglis, A.; Jasinkevica, I.; Kakurina, N.; Veze, I.; Volans, E.; Bagdonas, A.; Berukstis, E.; Celutkiene, J.; Dambrauskaite, A.; Jarasuniene, D.; Luksiene, D.; Rudys, A.; Sakalyte, G.; Sliaziene, S.; Aguilar-Romero, R.; Cardona-Muñoz, E.; Castro-Jimenez, J.; Chavez-Herrera, J.; Chuquiure Valenzuela, E.; De la Pena, G.; Herrera, E.; Leiva-Pons, J.; Lopez Alvarado, A.; Mendez Machado, G.; Ramos-Lopez, G.; Basart, D.; Buijs, E.; Cornel, J.; de Leeuw, M.; Dijkgraaf, R.; Dunselman, P.; Freericks, M.; Hamraoui, K.; Lenderlink, T.; Linssen, G.; Lodewick, P.; Lodewijks, C.; Lok, D.; Nierop, P.; Ronner, E.; Somsen, A.; van Dantzig, J.; van der Burgh, P.; van Kempen, L.; van Vlies, B.; Voors, A.; Wardeh, A.; Willems, F.; Dickstein, K.; Gundersen, T.; Hole, T.; Thalamus, J.; Westheim, A.; Dabrowski, M.; Gorski, J.; Korewicki, J.; Kuc, K.; Miekus, P.; Musial, W.; Niegowska, J.; Piotrowski, W.; Podolec, P.; Polonski, L.; Ponikowski, P.; Rynkiewicz, A.; Szelemej, R.; Trusz-Gluza, M.; Ujda, M.; Wojciechowski, D; Wysokinski, A.; Camacho, A.; Fonseca, C.; Monteiro, P.; Apetrei, E.; Bruckner, I.; Carasca, E.; Coman, I.; Datcu, M.; Dragulescu, S.; Ionescu, P.; Iordachescu-Petica, D.; Manitiu, I.; Popa, V.; Pop-Moldovan, A.; Radoi, M.; Stamate, S.; Tomescu, M.; Vita, I.; Aroutiounov, G.; Ballyuzek, M.; Bart, B.; Churina, S.; Glezer, M.; Goloshchekin, B.; Ivleva, A.; Kobalava, Z.; Kostenko, V.; Lopatin, Y.; Martynov, A.; Orlov, V.; Semernin, E.; Shogenov, Z.; Sidorenko, B.; Skvortsov, A.; Storzhakov, G.; Sulimov, V.; Talibov, O.; Tereshenko, S.; Tsyrline, V.; Zadionchenko, V.; Zateyshchikov, D.; Dzupina, A.; Hranai, M.; Kmec, J.; Micko, K.; Murin, J.; Pella, D.; Sojka, G.; Spisak, V.; Vahala, P.; Vinanska, D.; Badat, A.; Bayat, J.; Dawood, S.; Delport, E.; Ellis, G.; Garda, R.; Klug, E.; Mabin, T.; Naidoo, D.; Pretorius, M.; Ranjith, N.; Van Zyl, L.; Weich, H.; Anguita, M.; Berrazueta, J.; Bruguera i Cortada, J.; de Teresa, E.; Gómez Sánchez, M.; González Juanatey, J.; Gonzalez-Maqueda, I.; Jordana, R.; Lupon, J.; Manzano, L.; Pascual Figal, D.; Pulpón, L.; Recio, J.; Ridocci Soriano, F.; Rodríguez Lambert, J.; Roig Minguell, E.; Roig Minguell, E.; Romero, J.; Valdovinos, P.; Klintberg, L.; Kronvall, T.; Lycksell, M.; Morner, S.; Rydberg, E.; Swedberg, K.; Timberg, I.; Wikstrom, G.; Moccetti, T.4; Ashok, J.; Banerjee, P.; Carr-White, G.; Cleland, J.; Connolly, E.; Francis, M.; Greenbaum, R.; Kadr, H.; Lindsay, S.; McMurray, J.; Megarry, S.; Memon, A.; Murdoch, D.; Senior, R.; Squire, I.; Tan, L.; Witte, K.; Adams, K.; Adamson, P.; Adler, A.; Altschul, L.; Altschuller, A.; Amirani, H.; Anand, I.; Andreou, C.; Ansari, M.; Antonishen, M.; Banchs, H.; Banerjee, S.; Banish, D.; Bank, A.; Barbagelata, A.; Barnard, D.; Bellinger, R.; Benn, A.; Berk, M.; Berry, B.; Bethala, V.; Bilazarian, S.; Bisognano, J.; Bleyer, F.; Blum, M.; Boehmer, J.; Bouchard, A.; Boyle, A.; Bozkurt, B.; Brown, C.; Burlew, B.; Burnham, K.; Butler, J.; Call, J.; Cambier, P.; Cappola, T.; Carlson, R.; Chandler, B.; Chandra, R.; Chandraratna, P.; Chernick, R.; Colan, D.; Colfer, H.; Colucci, W.; Connelly, T.; Costantini, O.; Dadkhah, S.; Dauber, I.; Davis, J.; Davis, S.; Denning, S.; Drazner, M.; Dunlap, S.; Egbujiobi, L.; Elkayam, U.; Elliott, J.; El-Shahawy, M.; Essandoh, L.; Ewald, G.; Fang, J.; Farhoud, H.; Felker, G.; Fernandez, J.; Festin, R.; Fishbein, G.; Florea, V.; Flores, E.; Floro, J.; Gabris, M.; Garg, M.; Gatewood, R.; Geller, M.; Ghali, J.; Ghumman, W.; Gibbs, G.; Gillespie, E.; Gilmore, R.; Gogia, H.; Goldberg, L.; Gradus-Pizlo, I.; Grainger, T.; Gudmundsson, G.; Gunawardena, D.; Gupta, D.; Hack, T.; Hall, S.; Hamroff, G.; Hankins, S.; Hanna, M.; Hargrove, J.; Haught, W.; Hauptman, P.; Hazelrigg, M.; Herzog, C.; Heywood, J.; Hill, T.; Hilton, T.; Hirsch, H.; Hunter, J.; Ibrahim, H.; Imburgia, M.; Iteld, B.; Jackson, B.; Jaffrani, N.; Jain, D.; Jain, A.; James, M.; Jimenez, J.; Johnson, E.; Kale, P.; Kaneshige, A.; Kapadia, S.; Karia, D.; Karlsberg, R.; Katholi, R.; Kerut, E.; Khoury, W.; Kipperman, R.; Klapholz, M.; Kosinski, E.; Kozinn, M.; Kraus, D.; Krueger, S.; Krum, H.; Kumar, S.; Lader, E.; Lee, C.; Levy, W.; Lewis, E.; Light-McGroary, K.; Loh, I.; Lombardi, W.; Machado, C.; Maislos, F.; Mancini, D.; Markus, T.; Mather, P.; McCants, K.; McGrew, F.; McLaurin, B.; McMillan, E.; McNamara, D.; Meyer, T.; Meymandi, S.; Miller, A.; Minami, E.; Modi, M.; Mody, F.; Mohanty, P.; Moscoso, R.; Moskowitz, R.; Moustafa, M.; Mullen, M.; Naz, T.; Noonan, T.; O'Brien, T.; Oellerich, W.; Oren, R.; Pamboukian, S.; Pereira, N.; Pitt, W.; Porter, C.; Prabhu, S.; Promisloff, S.; Ratkovec, R.; Richardson, R.; Ross, A.; Saleh, N.; Saltzberg, M.; Sarkar, S.; Schmedtje, J.; Schneider, R.; Schuyler, G.; Shanes, J.; Sharma, A.; Siegel, C.; Siegel, R.; Silber, D.; Singh, V.; Singh, N.; Singh, J.; Sklar, J.; Small, R.; Smith, A.; Smith, E.; Smith, E.; Smull, D.; Sotolongo, R.; Staniloae, C.; Stapleton, D.; Steele, P.; Stehlik, J.; Stein, M.; Tang, W.; Thadani, U.; Torre-Amoine, G.; Trichon, B.; Tsai, C.; Tummala, R.; Van Bakel, A.; Vicari, R.; Vijay, N.; Vijayaraghavan, K.; Vittorio, T.; Vossler, M.; Wagoner, L.; Wallis, D.; Ward, N.; Widmer, M.; Wight, J.; Wilkins, C.; Williams, C.; Williams, G.; Winchester, M.; Winkel, E.; Wittmer, B.; Wood, D.; Wormer, D.; Wright, R.; Xu, Z.; Yasin, M.; Zolty, R.

    2013-01-01

    Aims This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Methods and results Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L. Conclusion The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. PMID:23329651

  12. Dornase alfa in the treatment of cystic fibrosis in Europe: a report from the Epidemiologic Registry of Cystic Fibrosis.

    PubMed

    Hodson, M E; McKenzie, S; Harms, H K; Koch, C; Mastella, G; Navarro, J; Strandvik, B

    2003-11-01

    Dornase alfa (Pulmozyme) treatment for patients with cystic fibrosis (CF) has been shown to improve pulmonary function and reduce exacerbations of infection in a number of placebo-controlled double-blind studies. Data in the Epidemiologic Registry of Cystic Fibrosis (ERCF) in November 1998 were used to assess the long-term effectiveness in routine clinical practice of dornase alfa in terms of pulmonary function and frequency of acute pulmonary exacerbations in CF. At that time, the ERCF contained data on 13,684 CF patients, with a mean observation period of 2.3 years. To be included in the analysis, patients had to have 2 years of data in the Registry in appropriate detail. Overall, untreated patients showed a decline in forced expiratory volume in 1 sec over a 2-year period of -2.3% predicted, but treated patients were stable, showing a change of 0.3% predicted, i.e., a treatment benefit of 2.5%. Compared to untreated patients, there were 25 fewer exacerbations per 100 treated patients per year. The analysis suggested that younger patients were likely to benefit more from treatment. The findings of randomized clinical trials were supported by the data collected in routine clinical practice.

  13. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

    PubMed

    Connolly, Stuart J; Milling, Truman J; Eikelboom, John W; Gibson, C Michael; Curnutte, John T; Gold, Alex; Bronson, Michele D; Lu, Genmin; Conley, Pamela B; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L; Siegal, Deborah M; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W Ting; Crowther, Mark

    2016-09-22

    Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. Results The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. Conclusions On the basis of a

  14. Arecibo pulsar survey using ALFA. III. Precursor survey and population synthesis

    SciTech Connect

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Senty, T. R.; Champion, D. J.; Lazarus, P.; Ransom, S. M.; Brazier, A.; Chatterjee, S.; Cordes, J. M.; Hessels, J. W. T.; Nice, D. J.; Ellis, J.; Allen, B.; Bhat, N. D. R.; Bogdanov, S.; Camilo, F.; Crawford, F.; Deneva, J. S.; and others

    2014-06-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° ≲ ℓ ≲ 77° and 168° ≲ ℓ ≲ 214°) close to the Galactic plane (|b| ≲ 5°) for pulsars. The PALFA survey is sensitive to sources fainter and more distant than have previously been seen because of Arecibo's unrivaled sensitivity. In this paper we detail a precursor survey of this region with PALFA, which observed a subset of the full region (slightly more restrictive in ℓ and |b| ≲ 1°) and detected 45 pulsars. Detections included 1 known millisecond pulsar and 11 previously unknown, long-period pulsars. In the surveyed part of the sky that overlaps with the Parkes Multibeam Pulsar Survey (36° ≲ ℓ ≲ 50°), PALFA is probing deeper than the Parkes survey, with four discoveries in this region. For both Galactic millisecond and normal pulsar populations, we compare the survey's detections with simulations to model these populations and, in particular, to estimate the number of observable pulsars in the Galaxy. We place 95% confidence intervals of 82,000 to 143,000 on the number of detectable normal pulsars and 9000 to 100,000 on the number of detectable millisecond pulsars in the Galactic disk. These are consistent with previous estimates. Given the most likely population size in each case (107,000 and 15,000 for normal and millisecond pulsars, respectively), we extend survey detection simulations to predict that, when complete, the full PALFA survey should have detected 1000{sub −230}{sup +330} normal pulsars and 30{sub −20}{sup +200} millisecond pulsars. Identical estimation techniques predict that 490{sub −115}{sup +160} normal pulsars and 12{sub −5}{sup +70} millisecond pulsars would be detected by the beginning of 2014; at the time, the PALFA survey had detected 283 normal pulsars and 31 millisecond pulsars, respectively. We attribute the deficiency in normal pulsar detections

  15. Arecibo Pulsar Survey Using ALFA. III. Precursor Survey and Population Synthesis

    NASA Astrophysics Data System (ADS)

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Champion, D. J.; Ransom, S. M.; Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Nice, D. J.; Ellis, J.; Senty, T. R.; Allen, B.; Bhat, N. D. R.; Bogdanov, S.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Freire, P. C. C.; Jenet, F. A.; Karako-Argaman, C.; Kaspi, V. M.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lynch, R.; Lyne, A. G.; Scholz, P.; Siemens, X.; Stairs, I. H.; Stappers, B. W.; Stovall, K.; Venkataraman, A.; Zhu, W. W.

    2014-06-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° <~ l <~ 77° and 168° <~ l <~ 214°) close to the Galactic plane (|b| <~ 5°) for pulsars. The PALFA survey is sensitive to sources fainter and more distant than have previously been seen because of Arecibo's unrivaled sensitivity. In this paper we detail a precursor survey of this region with PALFA, which observed a subset of the full region (slightly more restrictive in l and |b| <~ 1°) and detected 45 pulsars. Detections included 1 known millisecond pulsar and 11 previously unknown, long-period pulsars. In the surveyed part of the sky that overlaps with the Parkes Multibeam Pulsar Survey (36° <~ l <~ 50°), PALFA is probing deeper than the Parkes survey, with four discoveries in this region. For both Galactic millisecond and normal pulsar populations, we compare the survey's detections with simulations to model these populations and, in particular, to estimate the number of observable pulsars in the Galaxy. We place 95% confidence intervals of 82,000 to 143,000 on the number of detectable normal pulsars and 9000 to 100,000 on the number of detectable millisecond pulsars in the Galactic disk. These are consistent with previous estimates. Given the most likely population size in each case (107,000 and 15,000 for normal and millisecond pulsars, respectively), we extend survey detection simulations to predict that, when complete, the full PALFA survey should have detected 1000^{+330}_{-230} normal pulsars and 30^{+200}_{-20} millisecond pulsars. Identical estimation techniques predict that 490^{+160}_{-115} normal pulsars and 12^{+70}_{-5} millisecond pulsars would be detected by the beginning of 2014; at the time, the PALFA survey had detected 283 normal pulsars and 31 millisecond pulsars, respectively. We attribute the deficiency in normal pulsar detections predominantly to the radio frequency interference

  16. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months.

    PubMed

    Ida, Hiroyuki; Tanaka, Akemi; Matsubayashi, Tomoko; Murayama, Kei; Hongo, Teruaki; Lee, Hak-Myung; Mellgard, Björn

    2016-07-01

    Enzyme replacement therapy (ERT) with exogenous glucocerebrosidase is indicated to treat symptomatic Gaucher disease (GD), a rare, inherited metabolic disorder. ERT with velaglucerase alfa, which is produced in a human cell line using gene activation technology, was studied in a 12-month phase III trial in Japanese patients with type 1 or 3 GD who were switched from imiglucerase ERT (n=6); the current, open-label, 12-month extension study was designed to assess longer-term safety and efficacy. Two adult and three pediatric patients (aged <18years) were enrolled into the extension study. Every-other-week intravenous infusions were administered for 63-78weeks at average doses between 51.5 and 60.7units/kg. Three non-serious adverse events were considered related to velaglucerase alfa treatment, but no patient discontinued from the study. Six serious but non-drug-related adverse events were reported. No patient tested positive for anti-velaglucerase alfa antibodies. Hemoglobin concentrations, platelet counts, and liver and spleen volumes (normalized to body weight) in these patients were generally stable over a cumulative 24-month period from the baseline of the parent trial. The data suggest that velaglucerase alfa was well tolerated and maintained clinical stability in Japanese GD patients over 2years after switching from imiglucerase. ClinicalTrials.gov identifier NCT01842841. PMID:27241455

  17. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera

    PubMed Central

    Zagrijtschuk, Oleh; Buxhofer-Ausch, Veronika; Thaler, Josef; Schloegl, Ernst; Gastl, Guenther A.; Wolf, Dominik; Kralovics, Robert; Gisslinger, Bettina; Strecker, Karin; Egle, Alexander; Melchardt, Thomas; Burgstaller, Sonja; Willenbacher, Ella; Schalling, Martin; Them, Nicole C.; Kadlecova, Pavla; Klade, Christoph; Greil, Richard

    2015-01-01

    In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) α-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 µg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-α. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient. PMID:26261238

  18. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    PubMed

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take

  19. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

    PubMed Central

    Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B.; Enns, Gregory M.; Jones, Simon A.; Kane, John P.; Stock, Eveline O.; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S.; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A.; Sharma, Reena; Twelves, Chris; Whitley, Chester B.; Quinn, Anthony G.

    2014-01-01

    Background and aims Lysosomal Acid Lipase Deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results 216 infusions were administered to eight adult subjects through Week 52 during LAL-CL04. At Week 52, mean alanine aminotransferase and aspartate aminotransferase were normal with mean change from baseline of −58% and −40%. Mean change for low density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were −60%, −39%, −36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions Long-term dosing with sebelipase alfa in Lysosomal Acid Lipase-Deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). PMID:24993530

  20. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients(◆)

    PubMed Central

    Nelson, David R.; Zeuzem, Stefan; Andreone, Pietro; Ferenci, Peter; Herring, Robert; Jensen, Donald M.; Marcellin, Patrick; Pockros, Paul J.; Rodríguez-Torres, Maribel; Rossaro, Lorenzo; Rustgi, Vinod K.; Sepe, Thomas; Sulkowski, Mark; Thomason, Isaac R.; Yoshida, Eric M.; Chan, Anna; Hill, George

    2013-01-01

    Introduction Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin. Material and methods Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 μg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns. Results The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication. Conclusion Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439). PMID:22166557

  1. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    PubMed

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R

    2016-09-01

    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  2. The economic impact of epoetin alfa therapy on delaying time to dialysis in elderly patients with chronic kidney disease.

    PubMed

    Lefebvre, Patrick; Duh, Mei Sheng; Mody, Samir H; Bookhart, Brahim; Piech, Catherine Tak

    2007-02-01

    The aim of this study was to evaluate the impact of epoetin alfa (EPO) therapy on delaying progression to renal dialysis and quantify the associated medical cost savings in elderly chronic kidney disease (CKD) patients. Elderly (>/=65 years) dialysis patients who had >/=1 hemoglobin (Hb) value and >/=1 glomerular filtration rate (GFR) value of <60 mL/min/1.73 m(2) were identified using health claims and laboratory data from the period January 1999 to February 2005. Exclusion criteria included: organ transplantation, blood transfusion, use of darbepoetin alfa, and dialysis for reasons other than CKD. Each EPO patient was matched by Hb and GFR to one control patient. The time from when matched patients had the same GFR value to dialysis was compared. The economic impact of EPO on delaying dialysis was monetized using standardized health plan payments, and adjusted to 2005 United States dollars. Sixty-eight patients (34 EPO and 34 matched controls) formed the study population. The average time to dialysis was 156 days longer for the EPO group compared to the matched control group (p = 0.003). Analysis by CKD severity revealed that EPO therapy in less severe CKD patients offered a greater delay in time to dialysis (Stage 4: 213 days difference, p = 0.003; Stage 5: 104 days difference, p = 0.160). EPO treatment resulted in cost savings of $43,374-$59,222 per patient compared to non-EPO matched controls. This retrospective matched cohort study suggests that EPO therapy has a beneficial impact on delaying progression to dialysis in elderly CKD patients, especially in those with less severe CKD.

  3. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

    PubMed Central

    Jacobson, Ira; Zeuzem, Stefan; Flisiak, Robert; Knysz, Brygida; Lueth, Stefan; Zarebska-Michaluk, Dorota; Janczewska, Ewa; Ferenci, Peter; Diago, Moises; Zignego, Anna Linda; Safadi, Rifaat; Baruch, Yaacov; Abdurakhmanov, Dzhamal; Shafran, Stephen; Thabut, Dominique; Bruck, Rafael; Gadano, Adrian; Thompson, Alexander James; Kopit, Justin; McPhee, Fiona; Michener, Tracy; Hughes, Eric A; Yin, Philip D; Noviello, Stephanie

    2016-01-01

    AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients. METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin < 10 g/dL) and rash-related events, through week 12, were lower with daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the

  4. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes

    PubMed Central

    Gabrilove, Janice; Paquette, Ronald; Lyons, Roger M; Mushtaq, Chaudhry; Sekeres, Mikkael A; Tomita, Dianne; Dreiling, Lyndah

    2008-01-01

    Patients with myelodysplastic syndromes (MDS) often develop anaemia resulting in frequent transfusions and fatigue. Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anaemia. This single-arm, phase 2 study examined the efficacy of darbepoetin alfa 500 μg every 3 weeks (Q3W) for treating anaemia in low-risk MDS patients (after 6 weeks, poor responders received darbepoetin alfa 500 μg every 2 weeks). The primary end-point was the incidence of erythroid responses (International Working Group criteria) after 13 weeks of therapy. Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters. Analyses were stratified by the patient's previous ESA therapy status [ESA-naïve (n = 144) vs. prior ESA-treated (n = 62)]. After 13 weeks of therapy, 49% of ESA-naïve patients and 26% of prior ESA-treated patients achieved a major erythroid response. After 53/55 weeks, 59% of ESA-naïve patients and 34% of prior ESA-treated patients achieved a major erythroid response; 82% of ESA-naïve patients and 55% of prior ESA-treated patients achieved target haemoglobin of 110 g/l. Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported. In conclusion, darbepoetin alfa, 500 μg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients. PMID:18540943

  5. A Saudi Gastroenterology Association Position Statement on the Use of Tumor Necrosis Factor-alfa Antagonists for the Treatment of Inflammatory Bowel Disease

    PubMed Central

    Mosli, Mahmoud H.; Al-Harbi, Othman; Feagan, Brian G.; Almadi, Majid A.

    2015-01-01

    The objective of this position statement from the Saudi Gastroenterology Association is to guide gastroenterologists on the use of tumor necrosis factor-alfa (TNF-α) antagonists for the treatment of the idiopathic inflammatory bowel diseases, Crohn's disease, and ulcerative colitis. In this article, we summarize the relevant literature regarding the safety and efficacy of TNF-α antagonists, highlight relevant safety concerns specific to the environment in Saudi Arabia, and provide specific recommendations for the use of these agents. PMID:26228361

  6. 21 CFR 558.265 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... organic arsenic; drug overdose or lack of water intake may result in leg weakness or paralysis. Do not... organic arsenic; drug overdose or lack of water intake may result in leg weakness or paralysis. Do not... water fowl; avoid contact with skin, eyes, or clothing; keep out of lakes, ponds, or streams....

  7. 21 CFR 558.265 - Halofuginone hydrobromide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... use. (1) It is used in feed for broiler chickens as follows: (i) Amount. 2.72 grams per ton. (A... sole ration to replacement broiler breeder chickens until 16 weeks of age. Use as the sole source of... used in feed for replacement cage laying chickens and replacement broiler breeder chickens as...

  8. Influence of wool and thermo-binder fibers relative fractions on the adhesion of non-woven Alfa fibers reinforced unsaturated polyester hybrid composites

    NASA Astrophysics Data System (ADS)

    Amin Omri, Med; Triki, A.; Ben Hassen, Med; Arous, M.; Bulou, A.

    2016-10-01

    Alfa/wool/thermo-binder fibers hybrid composites were investigated in order to analyze adhesion state. Bearing in mind the chemical structure of wool and thermo-binder fibers, this study revealed a good compatibility between the reinforcement and the matrix. Dielectric measurements revealed the presence of two dielectric relaxations in the composite. The first relaxation was attributed to the α mode relaxation and the second one was associated with the conductivity noted for high temperature. This study allowed the analysis of the interfacial polarization effect using the Havrilliak-Negami model in the electric modulus formalism. The lowness of this relaxation intensity revealed a good adhesion of the fibers in the matrix. Differential Scanning Calorimetry (DSC) showed a slow decrease of the Tg glass transition temperature compared to the matrix, which could be explained by the existence of interactions between the fibers and the matrix. Vibrational analysis, based on FTIR measurements, showed a less hydrophilic character of Alfa fibers owing to a basic dissociation that occurs between the wool fibers and the water molecules associated with Alfa fibers. Furthermore, adhesion mechanism in the composite material was established by covalent and hydrogen bonds. Tensile testing performed on this composite confirmed that such adhesion was improved by increasing the thermo-binder fibers relative fraction.

  9. Efficacy and Safety of Danoprevir-Ritonavir plus Peginterferon Alfa-2a–Ribavirin in Hepatitis C Virus Genotype 1 Prior Null Responders

    PubMed Central

    Rouzier, Régine; Wiercinska-Drapalo, Alicja; Larrey, Dominique G.; Morcos, Peter N.; Brennan, Barbara J.; Le Pogam, Sophie; Nájera, Isabel; Petric, Rosemary; Tran, Jonathan Q.; Kulkarni, Rohit; Zhang, Ying; Smith, Patrick; Yetzer, Ellen S.; Shulman, Nancy S.

    2014-01-01

    Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a–ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a–ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10 reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a–ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10 decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a–ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had an IL28B non-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a–ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01185860.) PMID:24295986

  10. Biological modifiers (etretinate (changed from etetrinate) and alfa 2a) in the treatment of refractory cutaneous T-cell lymphoma.

    PubMed

    Avilés, A; Guzmán, R; García, E L; Díaz-Maqueo, J C

    1996-02-01

    To assess the efficacy and toxicity of biological modifiers in combination etetrinate, 0.8 mg/kg/day, po and interferon alfa 2a 9.0 MU, three times at week) in the treatment of refractory cutaneous T-cell lymphoma (CTLC) we began a clinical study on 12 heavily treated patients. After 1 year on treatment 10/12 patients (83%) achieved complete response. Two patients were considered failures with disease progression. After a median follow-up of 3 years, seven patients (56%) remained in complete remission. Toxicity was mild. All patients received 93% of the planned dose of etetrinate and interferon. We feel that biological modifiers, as etetrinate and interferons, are agents with limited hematological toxicity even in higher doses. The combination of two agents, with different mechanisms of action, could improve the outcome in patients with refractory CTCL. Controlled trials are necessary to define the roles of this type of therapy as first line of treatment. PMID:10851517

  11. Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

    PubMed Central

    Abbas, Zaigham; Memon, Mohammad Sadik; Umer, Muhammad Amir; Abbas, Minaam; Shazi, Lubna

    2016-01-01

    AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response. PMID:27190579

  12. Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

    PubMed

    Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Amorosa, Valerianna K; Wang, Crystal; Kang, Minhee; Matining, Roy; Zhang, Xiao; Dou, Diana; Umbleja, Triin; Kottilil, Shyam; Peters, Marion G

    2016-07-01

    A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ. PMID:26974581

  13. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    PubMed Central

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment.

  14. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

    PubMed Central

    Li, Ming-Hui; Xie, Yao; Zhang, Lu; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Mu, Cai-Qin; Hu, Lei-Ping; Hua, Wen-Hao; Song, Shu-Jing; Zhang, Shu-Feng; Cheng, Jun; Xu, Dao-Zhen

    2016-01-01

    AIM: To examine the association between interferon (IFN) therapy and loss of hepatitis B surface antigen (HBsAg) in inactive HBsAg carriers. METHODS: This was a retrospective cohort study in inactive HBsAg carriers, who were treatment-naive, with a serum HBsAg level < 100 IU/mL and an undetectable hepatitis B virus (HBV) DNA level (< 100 IU/mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBsAg, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen (65.0%) of 20 treated patients achieved HBsAg loss, 12 of whom achieved HBsAg seroconversion. Mean HBsAg level in treated patients decreased to 6.69 ± 13.04 IU/mL after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/mL. Serum HBV DNA level remained undetectable (< 100 IU/mL) in all treated patients during the study. HBsAg level of the control group decreased from 25.72 ± 25.58 IU/mL at baseline to 17.11 ± 21.62 IU/mL at week 96 (P = 0.108). In the control group, no patient experienced HBsAg loss/seroconversion, and two (5.0%) developed HBV reactivation. CONCLUSION: IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations. PMID:27239256

  15. An Open Label Comparison of Calfactant and Poractant Alfa Administration Traits and Impact on Neonatal Intensive Care Unit Resources

    PubMed Central

    Gerdes, Jeffrey S.; Seiberlich, William; Sivieri, Emidio M.; Marsh, Wallace; Varner, Dwight L.; Turck, Charles J; York, John M.

    2006-01-01

    OBJECTIVE To compare calfactant (CA) and poractant alfa (PA) administration traits, short-term clinical responses, and resource use in the neonatal respiratory distress syndrome (RDS) setting. METHODS An open label series of 277 (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered respiratory therapists collected patient, surfactant administration, and postadministration clinical data. Economic analysis involved labor costs of surfactant administration and usage, wastage, and product average wholesale price. Analysis utilized the Mann-Whitney rank sum test for differences in administration time and either the chi-square or Fisher's exact test for categorical variables. RESULTS PA had a statistically lower bedside administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P < .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8% vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher (13.2% vs. 3.5%; P < .001) with CA. Economic analyses found total administration costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were $141.21 for PA and $337.34 for CA (P < .001). CONCLUSIONS PA appeared to utilize fewer neonatal intensive care unit resources than CA due to reduced administration time and less wastage of drug product. Future studies should more closely evaluate time, resource, wastage, and post-administrative clinical effects to fully assess the impact of surfactant products in this setting. PMID:23118647

  16. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa.

    PubMed

    Liu, Chen-Hua; Kao, Jia-Horng

    2014-01-01

    Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility. PMID:24812506

  17. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    PubMed Central

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment. PMID:27695377

  18. Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase.

    PubMed

    Abian, Olga; Alfonso, Pilar; Velazquez-Campoy, Adrian; Giraldo, Pilar; Pocovi, Miguel; Sancho, Javier

    2011-12-01

    Gaucher disease (GD) is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal glucocerebrosidase (GlcCerase) activity, due to conformationally or functionally defective variants, resulting in progressive deposition of glycosylceramide in macrophages. The glucose analogue, N-butyldeoxynojirimycin (NB-DNJ, miglustat), is an inhibitor of the ceramide-specific glycosyltransferase, which catalyzes the first step of glycosphingolipid biosynthesis and is currently approved for the oral treatment of type 1 GD. In a previous work, we found a GlcCerase activity increase in cell cultures in the presence of NB-DNJ, which could imply that this compound is not only a substrate reducer but also a pharmacological chaperone or inhibitor for GlcCerase degradation. In this work we compare imiglucerase (the enzyme currently used for replacement therapy) and velaglucerase alfa (a novel therapeutic enzyme form) in terms of conformational stability and enzymatic activity, as well as the effect of NB-DNJ on them. The interaction between these enzymes and NB-DNJ was studied by isothermal titration calorimetry. Our results reveal that, although velaglucerase alfa and imiglucerase exhibit very similar activity profiles, velaglucerase alfa shows higher in vitro thermal stability and is less prone to aggregation/precipitation, which could be advantageous for storage and clinical administration. In addition, we show that at neutral pH NB-DNJ binds to and enhances the stability of both enzymes, while at mildly acidic lysosomal conditions it does not bind to them. These results support the potential role of NB-DNJ as a pharmacological chaperone, susceptible of being part of pharmaceutical formulation or combination therapy for GD in the future. PMID:21988669

  19. Benefit of Treatment Individualization in Patients with Chronic Hepatitis C Receiving Peginterferon Alfa-2a and Ribavirin in a Large Noninterventional Cohort Study

    PubMed Central

    Hofmann, Wolf Peter; Mauss, Stefan; Lutz, Thomas; Schober, Andreas; Böker, Klaus; Moog, Gero; Baumgarten, Axel; Pfeiffer-Vornkahl, Heike; Alshuth, Ulrich; Hüppe, Dietrich; Wedemeyer, Heiner; Manns, Michael P.; Schott, Eckart

    2015-01-01

    Background and Aims Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes. Methods From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization. Results Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period. Conclusions Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings. PMID:26230998

  20. Seven‐year safety and efficacy with velaglucerase alfa for treatment‐naïve adult patients with type 1 Gaucher disease

    PubMed Central

    Wang, Nan; Ogg, Carol; Crombez, Eric; Cohn, Gabriel M.; Elstein, Deborah

    2015-01-01

    Velaglucerase alfa is a human β‐glucocerebrosidase approved for Gaucher disease type 1 (GD1) treatment. This report summarizes the 7‐year experience of the now‐completed phase I/II and extension studies of adult GD1 patients who received velaglucerase alfa. Ten patients who completed the 9‐month, phase I/II study entered the extension trial TKT025EXT, of which eight completed this study. Doses were reduced after a cumulative treatment period of 15 to 18 months. Although all patients experienced ≥1 adverse event, no patient withdrew due to a drug‐related adverse event or required premedication. No patient developed anti‐drug antibodies, compliance remained high (median 98%), and seven of eight eligible patients transitioned to home infusions under supervision by healthcare professionals. Statistically significant improvements were observed for efficacy parameters: mean percentage changes from baseline (95% confidence intervals) were 18% (12%, 24%) for hemoglobin concentration, 115% (66%, 164%) for platelet counts, and −42% (−53%, −31%) and −78% (−94%, −62%) for liver and spleen volumes, respectively. Improvements were also observed for secondary endpoints chitotriosidase and CCL18 levels and exploratory endpoints (bone mineral density [BMD], bone marrow burden [BMB] scores). Normalization to near‐normalization of individuals' hemoglobin concentrations, platelet counts, liver volumes, and BMB scores was observed, and there were marked improvements in spleen volumes, biomarkers, and BMD. TKT025EXT represents the longest, prospective clinical trial for GD1 treatment to date and suggests that, despite dose reduction within 18 months of initiating therapy, velaglucerase alfa was generally well tolerated and was associated with marked improvement, including near normalization and/or normalization of key GD1 disease parameters. Am. J. Hematol. 90:577–583, 2015. © 2015 The Authors. American Journal of Hematology published by Wiley Periodicals

  1. Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase.

    PubMed

    Abian, Olga; Alfonso, Pilar; Velazquez-Campoy, Adrian; Giraldo, Pilar; Pocovi, Miguel; Sancho, Javier

    2011-12-01

    Gaucher disease (GD) is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal glucocerebrosidase (GlcCerase) activity, due to conformationally or functionally defective variants, resulting in progressive deposition of glycosylceramide in macrophages. The glucose analogue, N-butyldeoxynojirimycin (NB-DNJ, miglustat), is an inhibitor of the ceramide-specific glycosyltransferase, which catalyzes the first step of glycosphingolipid biosynthesis and is currently approved for the oral treatment of type 1 GD. In a previous work, we found a GlcCerase activity increase in cell cultures in the presence of NB-DNJ, which could imply that this compound is not only a substrate reducer but also a pharmacological chaperone or inhibitor for GlcCerase degradation. In this work we compare imiglucerase (the enzyme currently used for replacement therapy) and velaglucerase alfa (a novel therapeutic enzyme form) in terms of conformational stability and enzymatic activity, as well as the effect of NB-DNJ on them. The interaction between these enzymes and NB-DNJ was studied by isothermal titration calorimetry. Our results reveal that, although velaglucerase alfa and imiglucerase exhibit very similar activity profiles, velaglucerase alfa shows higher in vitro thermal stability and is less prone to aggregation/precipitation, which could be advantageous for storage and clinical administration. In addition, we show that at neutral pH NB-DNJ binds to and enhances the stability of both enzymes, while at mildly acidic lysosomal conditions it does not bind to them. These results support the potential role of NB-DNJ as a pharmacological chaperone, susceptible of being part of pharmaceutical formulation or combination therapy for GD in the future.

  2. Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy.

    PubMed

    Morón-López, Sara; Gómez-Mora, Elisabet; Salgado, Maria; Ouchi, Dan; Puertas, Maria C; Urrea, Víctor; Navarro, Jordi; Jou, Antoni; Pérez, Mercedes; Tural, Cristina; Clotet, Bonaventura; Montaner, Luis J; Blanco, Julià; Crespo, Manuel; Martinez-Picado, Javier

    2016-03-15

    Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4(+) T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2-long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation. PMID:26525407

  3. HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

    PubMed Central

    Ma, Hui; Yang, Rui-Feng; Li, Xiao-He; Jin, Qian; Wei, Lai

    2016-01-01

    Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN. Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10 kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU. PMID:27625094

  4. The H I mass function and velocity width function of void galaxies in the Arecibo Legacy Fast ALFA Survey

    NASA Astrophysics Data System (ADS)

    Moorman, Crystal M.; Vogeley, Michael S.; Hoyle, Fiona; Pan, Danny C.; Haynes, Martha P.; Giovanelli, Riccardo

    2014-11-01

    We measure the H I mass function (HIMF) and velocity width function (WF) across environments over a range of masses, 7.2ALFA (ALFALFA) Survey, located in the region of sky where ALFALFA and Sloan Digital Sky Survey (Data Release 7) North overlap. We divide our galaxy sample into those that reside in large-scale voids (void galaxies) and those that live in denser regions (wall galaxies). We find the void HIMF to be well fitted by a Schechter function with normalization Φ* = (1.37 ± 0.1) × 10-2y h3 Mpc-3, characteristic mass log(M_{H {I}^*/M_{⊙}) + 2 log h70 = 9.86 ± 0.02, and low-mass-end slope α = -1.29 ± 0.02. Similarly, for wall galaxies, we find best-fitting parameters Φ* = (1.82 ± 0.03) × 10-2 h3 Mpc-3, log(M_{H I}^*/M_{⊙}) + 2 log h70 = 10.00 ± 0.01, and α = -1.35 ± 0.01. We conclude that void galaxies typically have slightly lower H I masses than their non-void counterparts, which is in agreement with the dark matter (DM) halo mass function shift in voids assuming a simple relationship between DM mass and H I mass. We also find that the low-mass slope of the void HIMF is similar to that of the wall HIMF suggesting that there is either no excess of low-mass galaxies in voids or there is an abundance of intermediate H I mass galaxies. We fit a modified Schechter function to the ALFALFA void WF and determine its best-fitting parameters to be Φ* = 0.21 ± 0.1 h3 Mpc-3, log (W*) = 2.13 ± 0.3, α = 0.52 ± 0.5, and high-width slope β = 1.3 ± 0.4. For wall galaxies, the WF parameters are Φ* = 0.022 ± 0.009 h3 Mpc-3, log (W*) = 2.62 ± 0.5, α = -0.64 ± 0.2, and β = 3.58 ± 1.5. Because of large uncertainties on the void and wall WFs, we cannot conclude whether the WF is dependent on the environment.

  5. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348. PMID:24950666

  6. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.

  7. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    PubMed

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. PMID:23702393

  8. [Epoetin alfa in radiotherapy].

    PubMed

    Trodella, L; Balducci, M; Gambacorta, M A; Mantini, G

    1998-01-01

    Sixty per cent of oncologic patients need radiation therapy for cure or palliation. In fact, in most neoplastic diseases, a better local control positively impacts on disease-free survival and overall survival. The efficacy of radiotherapy depends on several factors: while some are tumor-related, others are host-related. Radiobiological phenomena are also important: ionizing radiation is responsible for cell damage (double rupture of DNA chains), mostly an indirect mechanism with the formation of free radicals. Their toxic action is enhanced by the oxygen partial pressure at the cellular level. A number of studies have confirmed that good tissue oxygenation is a function of a high hemoglobin level in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are rarely present in oncologic patients due to the disease-related toxicosis as well as to the therapy induced hematologic toxicity. The treatment of anemia is free of risk for the recent developments in technology which with gene cloning and the technique of recombinant DNA has allowed the production of human recombinant erythropoietin. Erythropoietin is produced by the interstitial cells of renal tubules in response to hypoxia. It prevents apoptosis and promotes erythroid proliferation and differentiation with consequent reticulocyte release and hemoglobin synthesis. It is not completely understood whether the efficacy of radiotherapy depends on hemoglobin values present at the start of irradiation (often less than 12-13 g/dL) or on the higher ones observed during and at the end of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non anemic patients in terms of costs/benefits is at present non sustainable. To the contrary, in patients undergoing radiotherapy to extended fields or aggressive multimodal treatments, for the higher risk of anemia, the early use of this treatment can be hypothesized in case of initial anemia to improve therapy compliance and prevent negative conditioning of results. Keeping in mind that grade 1 minimum toxicity for red cells, according to the Radiation Therapy Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be considered as cutoff to start erythropoietin therapy. PMID:10083890

  9. Epoetin Alfa Injection

    MedlinePlus

    ... vials. The multidose vials contain benzyl alcohol, a preservative that may be harmful to babies, so epoetin ... your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate

  11. A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study

    PubMed Central

    Rozov, Tatiana; Silva, Fernando Antônio A. e; Santana, Maria Angélica; Adde, Fabíola Villac; Mendes, Rita Heloisa

    2013-01-01

    OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the

  12. Rare Form of Erdheim-Chester Disease Presenting with Isolated Central Skeletal Lesions Treated with a Combination of Alfa-Interferon and Zoledronic Acid

    PubMed Central

    Bulycheva, E. N.; Baykov, V. V.; Zaraĭskiĭ, M. I.; Salogub, G. N.

    2015-01-01

    Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid. PMID:25949835

  13. Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases.

    PubMed

    Neidhart, J A; Anderson, S A; Harris, J E; Rinehart, J J; Laszlo, J; Dexeus, F H; Einhorn, L H; Trump, D L; Benedetto, P W; Tuttle, R L

    1991-05-01

    One hundred sixty-five patients were randomized to receive either interferon alfa-n1 (Wellferon; Burroughs Wellcome Co, Research Triangle Park, NC) alone or with vinblastine. An initial six-cycle induction treatment consisted of interferon given at daily doses of 3, 5, 20, 20, and 20 x 10(6) U/m2 every 2 weeks. Vinblastine at a dose of 10 mg/m2 (later decreased to 5 mg/m2) was given on day 1 of alternate cycles. Toxicities were generally well tolerated. The overall response rate was 10% with no significant difference between treatment arms. Survival was also not significantly different for the arms. A small subset of patients (16) with metastases only to the lungs had a high complete response (CR) and partial response (PR) rate of 44%. Responses were durable, and overall survival of this group was much better than that of the other patients. PMID:2016626

  14. Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

    PubMed Central

    Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

    2015-01-01

    This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755

  15. Action of propranolol in the reaction of smooth musculature of tracheal rings induced with acetylcholine, histamine, serotonin (5-HT) and prostaglandin (PGF2-alfa) in vitro and in vivo.

    PubMed

    Islami, Hilmi; Bexheti, Sadi; Ahmetaj, Halil; Sukalo, Aziz; Manxhuka, Suzana; Nuraj, Bajram; Kamberi, Xhevat; Krasniqi, Shaip; Qorraj, Hasime; Kastrati, Bashkim; Disha, Mentor

    2009-05-01

    Actions of acetylcholine (ACh), histamines, serotonins (5-HT) and prostaglandins (PGF2-alfa) in concentrations of 10(-4), 10(-3), 10(-2) and 10(-1) mol/dm(3) were analyzed in vitro conditions in isolated specimens of tracheas of 24 pigs, 7 guinea pigs, and dead persons for different reasons (8), in the presence and without presence of propranolol. Whilst, research regarding actions of aerosolized histamines (10 mg, 1%, 2 min), in the presence and without the presence of aerosolized propranolol (20 mg, 2%, 2 min) was done in vivo in 6 healthy persons. Study results show that propranolol does not emphasize contraction of the airways smooth musculature as induced by ACh, histamine, 5-HT and PGF2-alfa in vitro conditions (p>0,1). Also, in vivo we found a non-significance of tracheal smooth musculature constriction (p>0,1).

  16. Low-dose fludarabine with or without darbepoetin alfa in patients with chronic lymphocytic leukemia and comorbidity: primary results of the CLL9 trial of the German CLL Study Group.

    PubMed

    Goede, Valentin; Busch, Raymonde; Bahlo, Jasmin; Chataline, Viktoria; Kremers, Stephan; Müller, Lothar; Reschke, Daniel; Schlag, Rudolf; Schmidt, Burkhard; Vehling-Kaiser, Ursula; Wedding, Ulrich; Stilgenbauer, Stefan; Hallek, Michael

    2016-01-01

    This study was planned as a phase 3 trial to investigate low-dose fludarabine with or without darbepoetin alfa in older patients with previously untreated or treated chronic lymphocytic leukemia (CLL) and comorbidity. Due to slow recruitment, the study was terminated prematurely after accrual of 97 patients who, on average, were 74 years old and had a cumulative illness rating scale (CIRS) total score of 5. We report toxicity and efficacy of the study treatment. Grade 3-5 neutropenia and infection were observed in 25% and 10% of patients, respectively. Response was seen in 73% (5% complete remissions). Median event-free and overall survival was 12.2 and 44.8 months, respectively. No differences in outcome were found for patients treated with versus without darbepoetin alfa. In subjects with progressive/recurrent CLL during or after study treatment, overall survival was similar for patients receiving chemotherapy versus chemoimmunotherapy as salvage treatment. PMID:26293380

  17. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

    PubMed Central

    Goker-Alpan, Ozlem; Longo, Nicola; McDonald, Marie; Shankar, Suma P; Schiffmann, Raphael; Chang, Peter; Shen, Yinghua; Pano, Arian

    2016-01-01

    Background Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. Methods In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=−0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (−3.3, 3.7) g/m2.7; midwall fractional shortening, −0.62% (−2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (−11.4, 11.7) mL/min/1.73 m2; urine protein, −1.8 (−6.0, 2.4) mg/dL; urine microalbumin, 0.6 (−0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), −5.71 (−10.8, −0.6) nmol/mL; urinary Gb3, −1,403.3 (−3,714.0, 907.4) nmol/g creatinine

  18. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    PubMed Central

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich

    2008-01-01

    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  19. Impact of Epoetin Alfa on LV Structure, Function, and Pressure-Volume Relations as Assessed by Cardiac Magnetic Resonance – The Heart Failure Preserved Ejection Fraction (HFPEF) Anemia Trial

    PubMed Central

    Green, Philip; Babu, Benson A.; Teruya, Sergio; Helmke, Stephen; Prince, Martin; Maurer, Mathew S.

    2013-01-01

    Background Anemia, a common co-morbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. We quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. Methods Prospective, randomized single blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa versus placebo for 24 weeks in which a sub-group (n=22) had cardiac MRI at baseline and after 3 and 6 months to evaluate changes in cardiac structure and function. Pressure volume (PV) indices were derived from MRI measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated Results Subjects (75±10 years, 64% female) with HFPEF (EF=63±15%) with average hemoglobin of 10.3±1.1 gm/dl were treated with epoetin alfa using a dose adjusted algorithm that increased hemoglobin compared to placebo (p<0.0001). As compared to baseline, there were no significant changes in end diastolic (−7±8 vs. −3±8 ml, p=0.81) or end systolic (−0.4±2 vs. −0.7±5 ml, p= 0.96) volumes at 6 month follow-up between epoetin alfa compared with placebo. LV function as measured based on EF (−1.5±1.6% vs.−2.6±3.3%, p= 0.91) and pressure volume indices (PVa-iso-EDP at 30 mm Hg, −5071±4308 vs. −1662±4140 p=0.58) did not differ between epoetin alfa and placebo. Conclusion Administration of epoetin alfa to older adult patients with HFPEF resulted in a significant increase in hemoglobin, without evident change in LV structure, function, or pressure volume relationships as measured quantitatively using CMR. PMID:23517485

  20. A comparison of interferon alfa-2a and podophyllin in the treatment of primary condylomata acuminata. The Condylomata International Collaborative Study Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--to compare the response to treatment and recurrence rate of condylomata accuminata using subcutaneous injection of interferon alfa 2a 1.5 million units three times weekly for four weeks, or podophyllin resin 25% applied to lesions twice weekly for up to six weeks. DESIGN--Randomised open study. SETTING--Multicentre European study in genitourinary medicine, dermatovenereology, and gynaecology departments. PATIENTS--87 males and 67 females with condylomata acuminata for less than six months and no history of previous treatment. MAIN OUTCOME MEASURES--Complete clearance of lesions and evidence of recurrence at three months and nine months after treatment commenced. RESULTS--A complete response was achieved at three months in 15 of 64 (23%) in the interferon treated group, and 31 of 69 (45%) in the podophyllin treated group (p = 0.003). At nine months 10 of 13 patients in the interferon group and 22 of 30 patients in the podophyllin group remained completely clear of lesions. PMID:1743712

  1. Quantification of EVI1 transcript levels in acute myeloid leukemia by RT-qPCR analysis: A study by the ALFA Group.

    PubMed

    Smol, Thomas; Nibourel, Olivier; Marceau-Renaut, Alice; Celli-Lebras, Karine; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Terré, Christine; Thomas, Xavier; Castaigne, Sylvie; Dombret, Hervé; Preudhomme, Claude; Renneville, Aline

    2015-12-01

    EVI1 overexpression confers poor prognosis in acute myeloid leukemia (AML). Quantification of EVI1 expression has been mainly assessed by real-time quantitative PCR (RT-qPCR) based on relative quantification of EVI1-1D splice variant. In this study, we developed a RT-qPCR assay to perform quantification of EVI1 expression covering the different splice variants. A sequence localized in EVI1 exons 14 and 15 was cloned into plasmids that were used to establish RT-qPCR standard curves. Threshold values to define EVI1 overexpression were determined using 17 bone marrow (BM) and 31 peripheral blood (PB) control samples and were set at 1% in BM and 0.5% in PB. Samples from 64 AML patients overexpressing EVI1 included in the ALFA-0701 or -0702 trials were collected at diagnosis and during follow-up (n=152). Median EVI1 expression at AML diagnosis was 23.3% in BM and 3.6% in PB. EVI1 expression levels significantly decreased between diagnostic and post-induction samples, with an average variation from 21.6% to 3.56% in BM and from 4.0% to 0.22% in PB, but did not exceed 1 log10 reduction. Our study demonstrates that the magnitude of reduction in EVI1 expression levels between AML diagnosis and follow-up is not sufficient to allow sensitive detection of minimal residual disease.

  2. A new approach for ovarian stimulation in IVF using Corifollitropin Alfa in combination with GnRH analogues to trigger final oocyte maturation. A pilot study

    PubMed Central

    Decleer, W.; Osmanagaoglu, K.; Meganck, G.; Devroey, P.

    2014-01-01

    A pilot study of 10 patients undergoing IVF stimulation, using the new combination of Corifollitropin Alfa with highly purified hMG and GnRH antagonists has been performed, whereas final oocyte maturation was induced by GnRH analogues. The hormonal profiles were analyzed, as well as the clinical outcome. All patients were recruited between March 1st 2013 and June 30th 2013. They were all younger than 38 years, had a normal BMI (between 18,0 and 32,0) and did not have more than three previous IVF stimulations. The combination of long acting FSH with hphMG, and under protection of GnRH antagonists against spontaneous LH-surge, provided a normal hormonal profile for estradiol, progesterone, LH, and FSH. The average oocyte quality and embryo quality were excellent, which resulted in four pregnancies out of ten. We conclude that the described combination is a safe, efficient, and patient friendly alternative for the classical IVF stimulation. PMID:25374659

  3. A randomized controlled trial comparing darbepoetin alfa doses in red blood cell transfusion-dependent patients with low- or intermediate-1 risk myelodysplastic syndromes.

    PubMed

    Jang, Jun Ho; Harada, Hironori; Shibayama, Hirohiko; Shimazaki, Ryutaro; Kim, Hyeoung-Joon; Sawada, Kenichi; Mitani, Kinuko

    2015-10-01

    Darbepoetin alfa (DA) is a standard treatment for anemia in lower-risk MDS. However, to date there has been no comparative study to investigate the initial dosage. We, thus, conducted a randomized controlled trial to elucidate the optimal initial dosage of DA. International Prognostic Scoring System low or intermediate-1 risk MDS patients with hemoglobin levels ≤9.0 g/dL, serum erythropoietin levels ≤500 mIU/mL, and red blood cell transfusion dependency were enrolled. Patients were randomized to receive DA either at 60, 120, or 240 μg/week for 16 weeks followed by continuous administration with dose adjustment up to 48 weeks. Of 17, 18, and 15 patients in the 60, 120, and 240 μg DA groups included in the efficacy analysis, 64.7, 44.4, and 66.7 %, respectively, achieved the primary endpoint (major or minor erythroid response), while 17.6, 16.7, and 33.3 % achieved major erythroid responses in the initial 16-week period. No clinically significant safety concerns were identified. DA reduced the transfusion requirements effectively and safely in transfusion-dependent, lower-risk MDS patients. Given the highest achievement rate of the major erythroid response in the 240 μg group and the absence of dose-dependent adverse events, 240 μg weekly is the optimal initial dosage. PMID:26323997

  4. Determination of conformational and spectroscopic features of ethyl trans-alfa-cyano-3-indole-acrylate compound: an experimental and quantum chemical study.

    PubMed

    Cinar, Mehmet; Karabacak, Mehmet

    2013-03-01

    The optimized geometrical structure, vibrational and electronic transitions, chemical shifts and non-linear optical properties of ethyl trans-alfa-cyano-3-indole-acrylate (C(14)H(12)N(2)O(2)) compound were presented in this study. The ground state geometrical structure and vibrational wavenumbers were carried out by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational spectra of title compound were recorded in solid state with FT-IR and FT-Raman in the range of 4000-400 cm(-1) and 4000-10 cm(-1), respectively. The fundamental assignments were done on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The (1)H, (13)C and DEPT NMR spectra were recorded in DMSO solution, and gauge-invariant atomic orbitals (GIAO) method was used to predict the isotropic chemical shifts. The UV-Vis absorption spectra of the compound were recorded in the range of 200-800 nm in various solvents of different polarity (acetone, benzene, chlorobenzene, chloroform, DMSO, ethanol, methanol and toluene). Solvent effects were calculated using TD-DFT and CIS method. To investigate the non-linear optical properties, the polarizability, anisotropy of polarizability and molecular first hyperpolarizability were computed. A detailed description of spectroscopic behaviors of compound was given based on the comparison of experimental measurements and theoretical computations. PMID:23274474

  5. HCV quasispecies evolution during treatment with interferon alfa-2b and ribavirin in two children coinfected with HCV and HIV-1.

    PubMed

    Quesnel-Vallières, Mathieu; Lemay, Mireille; Lapointe, Normand; Martin, Steven R; Soudeyns, Hugo

    2008-10-01

    Two children who acquired hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection by mother-to-child transmission were monitored during interferon alfa-2b and ribavirin treatment. In Patient C1, CD4(+) T cell counts were within normal range and HIV-1 viral load was undetectable. HCV viral load declined slightly following treatment initiation while novel variants rapidly emerged, indicative of quasispecies diversification. In Patient C2, CD4(+) T cell counts were low and HIV-1 replication was not fully controlled by antiretroviral therapy. HCV viral load rose during treatment and a striking conservation of the variant spectrum was observed. In both cases, there was no decline in quasispecies complexity following treatment initiation and sustained virological response was not achieved. These results suggest that reduction in quasispecies complexity, which is observed in adult responders following interferon treatment, may be mechanistically unrelated with evolution of the variant profile and/or selective pressure exerted on HCV. PMID:18707918

  6. Impact of severe haemophilia A on patients' health status: results from the guardian(™) 1 clinical trial of turoctocog alfa (NovoEight(®) ).

    PubMed

    Ozelo, M; Chowdary, P; Regnault, A; Busk, A K

    2015-07-01

    Haemophilia and its treatment interfere with patients' life and may affect adherence to treatment. This study explored the impact of severe haemophilia A on patients' health status, especially in young adults (YA), using data from guardian(™) 1, a multinational, open-label, non-controlled phase 3 trial investigating safety and efficacy of turoctocog alfa (NovoEight(®) ) in previously treated patients aged 12 years and older with severe haemophilia A (FVIII ≤ 1%). Health status was assessed using the EuroQoL-5 dimensions (EQ-5D-3L), covering 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and a visual analogue scale (VAS) measuring self-rated overall health status. EQ-5D was administered pretreatment (screening/baseline) and posttreatment (end-of-trial). Baseline responses to the EQ-5D dimensions and VAS were described overall and by age and compared to reference values from UK general population. Guardian(™) 1 included 150 patients (16 adolescents, 83 YA aged 16-29 and 51 adults aged 30+). All five dimensions of patients' health status were impacted at baseline. The percentage of haemophilia patients reporting problems was consistently significantly greater than age-matched general population reference values. Likewise, for all age groups mean baseline EQ-5D VAS score was significantly lower for haemophilia patients (YA: 78.0) than for the general population (YA aged 18-29: 87.3). The health status of patients with severe haemophilia A entering guardian(™) 1 was markedly poorer than that of the general population, particularly regarding mobility and pain. YA patients reported better health status than older patients, but considerably lower than that of the general YA population.

  7. Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa.

    PubMed

    Jumbou, O; N'Guyen, J M; Tessier, M H; Legoux, B; Dréno, B

    1999-03-01

    Although interferon-alfa (IFN-alpha) has proved effective in treating epidermotropic cutaneous T-cell lymphoma (ECTL), few studies have considered the follow-up of treated patients and whether complete remission was maintained. We studied 51 patients (one stage Ia, seven stage Ib, one stage IIa, 30 stage IIb, 11 stage III (Sézary syndrome) and one stage IV) who received low-dose IFN-alpha as monotherapy for ECTL (mean daily dose of IFN-alpha 2.7 x 106 units for 14.9 months), giving special consideration to the significance of My7 (CD13) antigen expression by epidermal basal cells in predicting the maintenance of complete remission. For a mean follow-up period of 43.4 months, the results showed 21 complete remissions, 13 partial remissions and 17 patients with stable or progressive disease. Twelve patients died during the follow-up (3-52 months). IFN-alpha led to an improved response in the early stages, with a greater number of complete remissions (P = 0.03) and partial remissions (P = 0.01). The mean time to complete remission was 4 months, regardless of clinical stage (P = 0.1). Of 21 patients in complete remission, 57% had a relapse within a mean period of 7.5 months. For patients maintained in complete remission, the mean period of response was 31 months. The length of complete remission was independent of clinical stage, and My7 antigen expression was not predictive of complete remission.

  8. Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.

    PubMed

    Dasgupta, Nupur; Xu, You-Hai; Oh, Sunghee; Sun, Ying; Jia, Li; Keddache, Mehdi; Grabowski, Gregory A

    2013-01-01

    Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase) function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT) with the biosimilars, imiglucerase (imig) or velaglucerase alfa (vela) improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq) of no ERT and ERT (imig or vela) were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray), and DESeq and edgeR (mRNA-Seq). While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs) (∼3-fold) than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT biopharmaceuticals

  9. [Critical amino acids of ornitin decarboxylase degron: the presence and C-terminal arrangement is insufficient for alfa-fetoprotein degradation].

    PubMed

    Morozov, A V; Timofeev, A V; Morozov, V A; Karpov, V L

    2011-01-01

    Mouse ornithine decarboxylase (ODC) degrades in proteasome in an ubiquitin-independent manner with an averagehalf-life of 2 h. The 37 amino acid long C-terminal fragment known as a degradation signal (degron) is responsible for the effective degradation of ODC. Recently, amino acids being critical for degradation in the ODC-degron have been mapped. Mutations of Cys441 and Ala442 led to protein stabilization, while a substitution of other amino acids composing ODC-degron had almost no effect on the protein turnover; whereas insertions or deletions in region between Ala442 and ODC C-terminus diminished greatly rate of protein degradation, e.g. positioning of the key amino acids from the C-terminus was shown to be crucial. Using these data we introduced both key amino acids into the alfa-fetoprotein with truncated exportation signal (deltaAFP), at the same distance from the C-terminus as they being in the ODC (deltaAFPCAG and deltaAFPLCAG). Removal of N-terminal exportation signal prevented secretion of modified proteins. Using in silico approach we demonstrated no significant difference in hydrophobicity or secondary structure between C-terminus of deltaAFP and mutated proteins. The degradation kinetics of deltaAFP, deltaAFPCAG, deltaAFPLCAG in cyloheximide-chase and proteasome inhibition assay (using MG132) was identical. Obtained results suggest that introduced substitutions are insufficient for effective recognition of mutated deltaAFP by26S proteasome. We assume thatadditional amino aci ds composing ODC-degron or their combine action could also affect degradation. Besides that, one cannot exclude that conformation of the mutated deltaAFP limits its C-terminus accessibility to proteasome. PMID:21790016

  10. Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders.

    PubMed

    Polyzos, Nikolaos P; Corona, Roberta; Van De Vijver, Arne; Blockeel, Christophe; Drakopoulos, Panagiotis; Vloeberghs, Veerle; De Vos, Michel; Camus, Michel; Humaidan, Peter; Tournaye, Herman

    2015-01-01

    In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old), p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women, p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice. PMID:26172925

  11. Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b–based chemoradiation: ACOSOG Trial Z05031

    PubMed Central

    Picozzi, V. J.; Abrams, R. A.; Decker, P. A.; Traverso, W.; O'Reilly, E. M.; Greeno, E.; Martin, R. C.; Wilfong, L. S.; Rothenberg, M. L.; Posner, M. C.

    2011-01-01

    Background: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. Patients and methods: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m2 i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m2/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m2/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. Results: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0–20.1 months) and 25.4 months (95% CI 23.4–34.1 months), respectively. Conclusions: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects. PMID:20670978

  12. Assessment of the impact of treatment on quality of life of patients with haemophilia A at different ages: insights from two clinical trials on turoctocog alfa.

    PubMed

    Santagostino, E; Lentz, S R; Busk, A K; Regnault, A; Iorio, A

    2014-07-01

    Haemophilia and its treatment interfere with patients' life, so health-related quality of life (HRQoL) should be assessed when evaluating treatments. This study investigated the HRQoL of patients with haemophilia A treated prophylactically with a new recombinant factor VIII. Two phase 3 trials investigated turoctocog alfa in patients with severe haemophilia A: one in children, one in adults and adolescents. HRQoL was a secondary endpoint assessed by the HAEMO-QOL age-specific, self-administered questionnaires. Parent-completed versions were also included for parents of children and adolescents. All HAEMO-QOL questionnaires allow the calculation of domain-specific and total scores ranging from 0 to 100, lower scores indicating better HRQoL. Mean change in all scores was described for 25 children aged 4-7 years, 21 children aged 8-12 years, 18 adolescents aged 13-18 years and 129 adults, overall, and according to the treatment regimen received prior to the study (on-demand; prophylaxis; mixed). Mean changes in HAEMO-QOL total score were 1.4 for children aged 4-7 years, -2.6 for children aged 8-12 years, -5.8 for adolescents and -1.6 for adults. In parent-completed versions, mean changes in total score were -6.0 for children aged 4-7 years, -4.7 for children aged 8-12 years, and -10.0 for adolescents. Patients receiving on-demand treatment before the trial showed greater improvement in HRQoL scores than patients already on prophylaxis. HRQoL of patients remained fairly stable over the course of the trials. However, improvements were observed for adolescents. Switching to prophylaxis was identified as a potential driver of improvement of HRQoL in patients with haemophilia A.

  13. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

    PubMed

    Wadler, S; Lembersky, B; Atkins, M; Kirkwood, J; Petrelli, N

    1991-10-01

    In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID:1919631

  14. Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies

    PubMed Central

    Wedemeyer, Heiner; Forns, Xavier; Hézode, Christophe; Lee, Samuel S.; Scalori, Astrid; Voulgari, Athina; Le Pogam, Sophie; Nájera, Isabel; Thommes, James A.

    2016-01-01

    Most patients with chronic hepatitis C virus (HCV) genotype 1 infection who have had a previous null response (<2-log10 reduction in HCV RNA by treatment week 12) to peginterferon/ribavirin (PegIFN/RBV) do not achieve a sustained virological response (SVR) when re-treated with a first-generation HCV protease inhibitor (PI) administered in combination with PegIFN/RBV. We studied the incremental benefits associated with adding mericitabine (nucleoside analog inhibitor of HCV polymerase) to PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomized multicenter phase 2 trials (with boceprevir in DYNAMO 1, and with telaprevir in DYNAMO 2). The primary endpoint in both trials was SVR, defined as HCV RNA <25 IU/mL 12 weeks after the end of treatment (SVR12). Overall, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60–70% in DYNAMO 1 and of 71–96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials. The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial. The addition of mericitabine did not add to the safety burden associated with either telaprevir or boceprevir-based regimens. These studies demonstrate increased SVR rates and reduced relapse rates in difficult-to-treat patients when a nucleoside polymerase inhibitor with intermediate antiviral potency is added to regimens containing a first-generation PI. Trial Registration: ClinicalTrials.gov NCT01482403 and ClinicalTrials.gov NCT01482390 PMID:26752189

  15. Interferon Alfa-2b Injection

    MedlinePlus

    ... medication either subcutaneously or intramuscularly three times a week. HBV, inject the medication either subcutaneously or intramuscularly three times a week usually for 16 weeks. hairy cell leukemia, inject ...

  16. HBsAg seroconversion after pegylated interferon alfa 2a rescue in a lamivudine-resistant patient with HBeAg-negative chronic hepatitis B and favourable IL28-B genotype.

    PubMed

    Stanzione, Maria; Stornaiuolo, Gianfranca; Rizzo, Viviana; Pontarelli, Agostina; Gaeta, Giovanni Battista

    2016-06-01

    Hepatitis B virus (HBV) surface antigen (HBsAg) seroconversion to anti-HBs antibody is the best final objective for all available chronic hepatitis B (CHB) treatments. Unfortunately, this goal is rarely achieved with the currently applied therapeutic approaches. Here we describe the case of an anti-HBe-positive CHB patient who was successfully treated with a particular therapeutic schedule. The patient was initially treated with lamivudine (LAM) for nine years. Breakthrough was observed after eight years of LAM therapy. HBV-DNA was 3x10E4 IU/mL and LAM resistance mutations were present. Subcutaneous pegylated interferon (PEG-IFN) alfa 2a, 180 mcg/week, was added to LAM and after 4 weeks LAM was discontinued and PEG-IFN alone was continued up to week 52. HBV-DNA became undetectable at week 4 of therapy; serum HBsAg started to decline from week 4 and became undetectable at week 36, with the subsequent appearance of anti-HBs antibodies. IL28-B was genotyped at the polymorphic site rs12979860 and the CC allele was detected. Rescue therapy with Peg-IFN may be an option for selected patients with resistance to nucleos(t)ide analogues. PMID:27367326

  17. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus (HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15546256

  18. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus(HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15641210

  19. Bone Marrow Stromal Cells Protect Lymphoma B-cells from Rituximab-Induced Apoptosis and Targeting Integrin alfa-4-beta-1 (VLA-4) with Natalizumab can Overcome this Resistance

    PubMed Central

    Mraz, Marek; Zent, Clive S.; Church, Amy K.; Jelinek, Diane F.; Wu, Xiaosheng; Pospisilova, Sarka; Ansell, Stephen M.; Novak, Anne J.; Kay, Neil E.; Witzig, Thomas E.; Nowakowski, Grzegorz S.

    2011-01-01

    Rituximab improves the outcome of patients with non-Hodgkin lymphoma, but does not completely eradicate residual B-cell populations in the microenvironment of the bone marrow and lymph nodes. Adhesion to stromal cells can protect B-cells from apoptosis induced by chemotherapy drugs (cell adhesion-mediated drug resistance; CAM-DR). A similar mechanism of resistance to rituximab has not, to our knowledge, been described. We tested the hypothesis that the microenvironment protects malignant B-cells from rituximab-induced apoptosis, and that blocking these interactions with natalizumab, an antibody targeting VLA-4 (integrin alfa-4-beta-1/CD49d), can overcome this protection. VLA-4 is an adhesion molecule constitutively expressed on malignant B-cells and is important for pro-survival signalling in the bone marrow and lymph node microenvironment. The human bone marrow stromal cell line HS-5 was shown to strongly protect B-cell lymphoma cells from rituximab cytotoxicity, suggesting the existence of a stromal cell adhesion-mediated antibody resistance (CAM-AR) mechanism analogous to CAM-DR. Natalizumab decreased B-lymphocyte adherence to fibronectin by 75-95% and partially overcame stromal protection against rituximab and cytotoxic drugs. These pre-clinical findings suggest that the addition of stromal adhesion-disruptive drugs to rituximab-containing therapy could improve treatment efficacy. PMID:21749361

  20. Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Patients With Chemotherapy-Associated Anemia

    PubMed Central

    Steensma, David P.; Sloan, Jeff A.; Dakhil, Shaker R.; Dalton, Robert; Kahanic, Stephen P.; Prager, Diane J.; Stella, Philip J.; Rowland, Kendrith M.; Novotny, Paul J.; Loprinzi, Charles L.

    2011-01-01

    Purpose Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA. Patients and Methods This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks. Results There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16). Conclusion In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo. PMID:21098317

  1. Single-dose pharmacokinetics of bupropion hydrobromide and metabolites in healthy adolescent and adult subjects.

    PubMed

    Oh, D Alexander; Crean, Christopher S

    2015-09-01

    Data from 2 pediatric single-dose studies, conducted at the same center, were combined to evaluate exposure levels of bupropion and metabolites in adolescents 12-17 years old, compared with adults > 18 years. Pharmacokinetic analyses of bupropion and its metabolites were performed using normalization and pharmacological/convulsive weighting methods on exposure. When compared with adults (>18 years), subjects 12-14 years had an increase in weight-normalized exposure to bupropion (ie, Cmax , 78%; AUC0-t , 83%; and AUCinf , 85%). Variability in this younger age group was also higher, with observations of a 3- to 4-fold increase in exposure. When the changes in metabolites were accounted within pharmacological and convulsive-weighted exposures, the relative ratio of 12-14 years to adults in body weight-normalized Cmax was 127% and 110%, respectively. Subjects 15-17 years did not exhibit a difference in exposure compared with adults. The influence of age on bupropion pharmacokinetics demonstrates that, in general, healthy adolescent subjects cannot be considered smaller healthy adult subjects; the increase in exposure is inversely related to age and appears to be solely associated with bupropion, not with its metabolites. Because there are no clinical safety and efficacy data of bupropion in adolescents, this data may shift its risk-benefit profile. PMID:27137143

  2. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    PubMed Central

    Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G. Douglas; Teot, Lisa A.; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C.; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M.; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C.W.; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R.; Bernstein, Mark

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped

  3. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  4. ALF--a simulation framework for genome evolution.

    PubMed

    Dalquen, Daniel A; Anisimova, Maria; Gonnet, Gaston H; Dessimoz, Christophe

    2012-04-01

    In computational evolutionary biology, verification and benchmarking is a challenging task because the evolutionary history of studied biological entities is usually not known. Computer programs for simulating sequence evolution in silico have shown to be viable test beds for the verification of newly developed methods and to compare different algorithms. However, current simulation packages tend to focus either on gene-level aspects of genome evolution such as character substitutions and insertions and deletions (indels) or on genome-level aspects such as genome rearrangement and speciation events. Here, we introduce Artificial Life Framework (ALF), which aims at simulating the entire range of evolutionary forces that act on genomes: nucleotide, codon, or amino acid substitution (under simple or mixture models), indels, GC-content amelioration, gene duplication, gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer (LGT), or speciation. The other distinctive feature of ALF is its user-friendly yet powerful web interface. We illustrate the utility of ALF with two possible applications: 1) we reanalyze data from a study of selection after globin gene duplication and test the statistical significance of the original conclusions and 2) we demonstrate that LGT can dramatically decrease the accuracy of two well-established orthology inference methods. ALF is available as a stand-alone application or via a web interface at http://www.cbrg.ethz.ch/alf.

  5. 75 FR 15642 - Schedules of Controlled Substances: Exempted Prescription Product; River Edge Pharmaceutical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide. The Deputy Assistant Administrator, Office..., atropine sulfate and scopolamine hydrobromide. These ingredients are not controlled substances. In...

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, adalimumab, AERx morphine sulphate, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, almotriptan, amprenavir, aripiprazole, atenolol, atorvastatin calcium; BSYX-A110; Cantuzumab mertansine, capravirine, CDP-571, CDP-870, celecoxib; Delavirdine mesilate, docetaxel, dofetilide, donepezil hydrochloride, duloxetine hydrochloride, dutasteride, dydrogesterone; Efavirenz, emtricitabine, enjuvia, enteryx, epristeride, erlotinib hydrochloride, escitalopram oxalate, etanercept, etonogestrel, etoricoxib; Fesoterodine, finasteride, flt3ligand; Galantamine hydrobromide, gemtuzumab ozogamicin, genistein, gepirone hydrochloride; Indinavir sulfate, infliximab; Lamivudine, lamivudine/zidovudine/abacavir sulfate, leteprinim potassium, levetiracetam, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, losartan potassium; MCC-465, MRA; Nebivolol, nesiritide, nevirapine; Olanzapine, OROS(R)-Methylphenidate hydrochloride; Peginterferon alfa-2a, peginterferon alfa-2b, Pimecrolimus, polyethylene glycol 3350, pramlintide acetate, pregabalin, PRO-2000; Risedronate sodium, risperidone, ritonavir, rituximab, rivastigmine tartrate, rofecoxib, rosuvastatin calcium; Saquinavir mesilate, Stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, telmisartan, tomoxetine hydrochloride, treprostinil sodium, trimegestone, trimetrexate; Valdecoxib, venlafaxine hydrochloride; Zoledronic acid monohydrate. PMID:12616965

  7. Conformational comparison of 1,2-dimethyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile free base and its hydrobromide monohydrate salt.

    PubMed

    Cody, V; Suwínska, K; Wojtczak, A

    1991-01-15

    C13H11N3O (I), Mr = 225.25, monoclinic, P21/c, a = 11.713 (4), b = 7.891 (3), c = 12.154 (4) A, beta = 92.27 (4) degrees, V = 1123 (1) A3, Z = 4, Dx = 1.333 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.082 mm-1, F(000) = 472, T = 293 K, R = 0.063 for 2579 reflections. 5-cyano-1,2-dimethyl-6-oxo-1,6-dihydro-3,4'-bipyridinium bromide monohydrate, C13H12N3O+.Br-.H2O (II), Mr = 324.18, orthorhombic, Pbca, a = 7.2893 (8), b = 18.955 (3), c = 19.814 (3) A, V = 2738 (1) A3, Z = 8, Dx = 1.573 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 2.972 mm-1, F(000) = 1312, T = 293 K, R = 0.086 for 2292 reflections. The twist angle around the bipyridine C(1)-C(1)' bond is 66.6 (2) and 44.1 (8) degrees for the free base (I) and its salt (II), respectively. The larger C(3)'-N(4)'-C(5)' pyridine ring angle [121.8 (5) degrees] in the salt structure compared with the corresponding value for the free base [116.1 (1) degrees] suggests that N(4)' is a protonation site. The water molecule in the salt structure (II) is disordered with occupancy refined to 0.6 and 0.4.

  8. Interleukin-12 Followed by Interferon Alfa in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-01-31

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  9. Infection and inflammation in patients on dialysis: an underlying contributor to anemia and epoetin alfa hyporesponse.

    PubMed

    Breiterman-White, Randee

    2006-01-01

    Acute or chronic infections or inflammatory conditions can exacerbate anemia in patients on dialysis. The primary goal is to identify and treat the underlying disorder, while minimizing the impact on hemoglobin (Hb) levels. Nurses can be instrumental in minimizing the impact of these conditions by monitoring the longitudinal trends in Hb levels, proactively assessing patients for inflammatory or infectious conditions, and intervening to resolve causative conditions and minimize the impact on anemia.

  10. Differential Dynamics of CALR Mutant Allele Burden in Myeloproliferative Neoplasms during Interferon Alfa Treatment

    PubMed Central

    Holmström, Morten O.; Thomassen, Mads; Kruse, Torben A; Pallisgaard, Niels; Larsen, Thomas S.; de Stricker, Karin; Skov, Vibe; Hasselbalch, Hans C.

    2016-01-01

    Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients. We investigated the response to IFN in a cohort of 21 CALR mutated MPN patients including ET, prefibrotic primary myelofibrosis (pre-PMF), and primary myelofibrosis (PMF) with a median follow-up of 31 months. For evaluation of a molecular response, we developed highly sensitive quantitative PCR (qPCR) assays for monitoring the mutant allele burden of the two most prevalent CALR mutations (type 1 and type 2). Thirteen patients (62%) experienced a decrease in the mutant allele burden with a median decline of 29% from baseline. However, only four patients, including patients with ET, pre-PMF, and PMF diagnosis, achieved molecular responder (MR) status with >50% reduction in mutant allele burden according to European LeukemiaNet (ELN) guidelines. MR patients displayed significant differences in the dynamics of the CALR mutant load with regard to time to response and dynamics in mutant allele burden after discontinuation of IFN treatment. Furthermore, we highlight the prognostic value of the CALR mutant allele burden by showing a close association with leucocyte- and platelet counts, hemoglobin concentration, in addition to plasma lactate dehydrogenase (LDH) irrespective of molecular response and treatment status. PMID:27764253

  11. Interleukin-2 Plus Interferon Alfa in Treating Adults With Metastatic Cancer

    ClinicalTrials.gov

    2011-05-10

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Unspecified Adult Solid Tumor, Protocol Specific

  12. HI Absorption Lines Detected from the Arecibo Legacy Fast ALFA Survey Data

    NASA Astrophysics Data System (ADS)

    Zhong-zu, Wu; Martha P, Haynes; Riccardo, Giovanelli; Ming, Zhu; Ru-rong, Chen

    2015-10-01

    We present some preliminary results of an on-going study of HI 21-cm absorption lines based on the 40% survey data released by the Arecibo Legacy Fast Arecibo L-band Feed Array (ALFALFA). (1) Ten HI candidate absorbers have been detected. Five of them are previously published in the literature, and the rest of them are new detections that need further confirmation. (2) For those sources with no detected absorptions, we have calculated the upper limit of their foreground HI column density NHI. The statistical result of the NHI distribution indicates that the ratio Ts/f between the averaged spin temperature and coverage factor for DLAs (the damped Lyα systems) might be larger than 500 K. The radio frequency interference (RFI) and standing wave are the main factors affecting the detection of HI absorption lines, which have been analyzed and discussed as well in order to find a method of solution. Our study can serve as a pathfinder for the future large-scale search of HI 21-cm absorption lines using the Five-Hundred-Meter Aperture Spherical Radio Telescope (FAST), which is an Arecibo-type radio telescope currently under construction in China with greatly increased sensitivity, bandwidth, and observational sky area. As prospects, we have discussed two types of observational studies of HI absorption lines toward extragalactic sources using the FAST telescope.

  13. Epoetin Alfa in Treating Anemia in Patients Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-07-12

    Anemia; Breast Cancer; Chronic Myeloproliferative Disorders; Drug/Agent Toxicity by Tissue/Organ; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  14. [Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex, Colombia].

    PubMed

    Medina-Rangel, Guido Fabián

    2011-06-01

    Diversity is a property of community that can described, characterized, and understood according to the functioning of ecosystems. To study the richness and local abundance and species replacement between habitats around the Zapatosa's wetland complex (El Cesar Department), I carried out four field trips between November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove and tree-lined savanna; with the exception of the palm-grove sampled at its 75%, the others were sampled up to their 80%. I found 847 reptiles that were distributed in 48 species. The group with the highest number of species was Colubridae with 14, followed by Gekkonidae with five. Five endemic species and eight with some conservation threat grade at a national level are reported. The riparian forest was the richest and most abundant habitat with 34 species and 196 individuals. For each habitat, Colubridae had the highest number of species, followed by the families Polychrotidae, Gekkonidae and Teiidae, in that order. The reptile species composition was not different between the tree-lined savanna and the chasmophyte forest, but differed among the tree-lined savanna and the riparian forest, palm-grove and dry forest habitats. The most important differences in the species composition among almost all the habitats were influenced by the species Anolis tropidogaster and Gonatodes albogularis, and the higher occurrence of Stenocercus erythrogaster in the chasmophyte forest. The species replacement had an average value of 50%; the biggest amounts of shared species were the lizards, while the snake Leptodeira septentrionalis was the only one present in all habitat types. The forest grows-among-rocks showed the biggest complementarity and number of unique species compared to the other habitats. The wetland complex provides two thirds of the reptile's species reported until now for the Caribbean region, and more than 80% of those reported for the El Cesar department. This wetland complex seems to behave as a center for low land species concentration as it hosts a high proportion of species from those places.

  15. Dinamica numerica di microsonde verso Alfa Centauri con impulsi LASER su vele spaziali

    NASA Astrophysics Data System (ADS)

    Sigismondi, Costantino

    2016-05-01

    Starshot project aims to reach alpha Centauri at 4.4 light years in 24 years, by accelerating to velocity 0.2 c with collimated LASER light pressure for 1000s several grams-scale microprobes with space sails. The energetics and dynamical equations are solved numerically on a worksheet and discussed.

  16. The Arecibo Legacy Fast ALFA Survey: The Galaxy Population Detected by ALFALFA

    NASA Astrophysics Data System (ADS)

    Huang, Shan; Haynes, Martha P.; Giovanelli, Riccardo; Brinchmann, Jarle

    2012-09-01

    Making use of H I 21 cm line measurements from the ALFALFA survey (α.40) and photometry from the Sloan Digital Sky Survey (SDSS) and Galaxy Evolution Explorer (GALEX), we investigate the global scaling relations and fundamental planes linking stars and gas for a sample of 9417 common galaxies: the α.40-SDSS-GALEX sample. In addition to their H I properties derived from the ALFALFA data set, stellar masses (M *) and star formation rates (SFRs) are derived from fitting the UV-optical spectral energy distributions. 96% of the α.40-SDSS-GALEX galaxies belong to the blue cloud, with the average gas fraction f H I ≡ M H I /M * ~ 1.5. A transition in star formation (SF) properties is found whereby below M * ~ 109.5 M ⊙, the slope of the star-forming sequence changes, the dispersion in the specific star formation rate (SSFR) distribution increases, and the star formation efficiency (SFE) mildly increases with M *. The evolutionary track in the SSFR-M * diagram, as well as that in the color-magnitude diagram, is linked to the H I content; below this transition mass, the SF is regulated strongly by the H I. Comparison of H I and optically selected samples over the same restricted volume shows that the H I-selected population is less evolved and has overall higher SFR and SSFR at a given stellar mass, but lower SFE and extinction, suggesting either that a bottleneck exists in the H I-to-H2 conversion or that the process of SF in the very H I-dominated galaxies obeys an unusual, low-efficiency SF law. A trend is found that, for a given stellar mass, high gas fraction galaxies reside preferentially in dark matter halos with high spin parameters. Because it represents a full census of H I-bearing galaxies at z ~ 0, the scaling relations and fundamental planes derived for the ALFALFA population can be used to assess the H I detection rate by future blind H I surveys and intensity mapping experiments at higher redshift. Based on observations made with the Arecibo Observatory. The Arecibo Observatory is operated by SRI International under a cooperative agreement with the National Science Foundation (AST-1100968) and in alliance with Ana G. Méndez-Universidad Metropolitana and the Universities Space Research Association.

  17. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  18. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  19. 49 CFR Appendix A to Part 593 - List of Vehicles Determined to be Eligible for Importation

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 2012 55 Alfa Romeo 164 1989 196 Alfa Romeo 164 1991 76 Alfa Romeo 164 1994 156 Alfa Romeo Spider 1992... Ferrari 348 TS 1992 161 Ferrari 360 2001 376 Ferrari 360 Spider & Coupe 2003 410 Ferrari 360...

  20. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  1. [POLYMORPHISM OF ALFA-AMYLASE AND CONJUGATION IN COMMON WHEAT ENZYME TYPES WITH QUANTITATIVE TRAITS OF PLANTS].

    PubMed

    Netsvetaev, V P; Bondarenko, L S; Motorina, I P

    2015-01-01

    Using polymorphism of alpha-amylase in the winter common wheat studied inheritance isoenzymes and its conjugation enzyme types with germinating grain on the "vine", grain productivity, plant height and time of ear formation. It is shown that the polymorphism isoenzyme of alpha-amylase wheat is limited by the presence of different loci whose products are similar in electrophoretic parameters. In this regard, one component of the enzyme can be controlling at one or two or three genes. Identification of a locus controlling alpha-amylase isoenzyme in the fast moving part of the electrophoretogram, designated as α-Amy-B7. Determine the distance of the locus to factor α-Amy-B6.

  2. Risk of Orthopedic Surgical Site Infections in Patients with Rheumatoid Arthritis Treated with Antitumor Necrosis Factor Alfa Therapy

    PubMed Central

    da Cunha, Bernardo Matos; Maria Henrique da Mota, Licia; dos Santos-Neto, Leopoldo Luiz

    2012-01-01

    Introduction. International guidelines recommend interruption of anti-TNF medications in the perioperative period, but there are no randomized trials to support such recommendation. Objectives. To study literature evidence assessing the risk of surgical site infections in orthopedic surgery patients with RA using anti-TNF drugs, compared to untreated patients or those using conventional DMARD. Methods. Systematic review of cohort studies is concerning surgical site infections in orthopedic procedures in patients with RA. Results. Three studies were selected. Only one was considered of high-quality, albeit with low statistical power. The review resulted in inconclusive data, since the best quality study showed no significant differences between groups, while others showed increased risk of infections in patients using anti-TNF medications. Conclusion. It is unclear whether patients with RA using anti-TNF medications are at increased risk of surgical site infections. Randomized controlled trials or new high quality observational studies are needed to clarify the issue. PMID:22500176

  3. Gas-rich Galaxies in the Arecibo Legacy Fast ALFA Survey (ALFALFA) -- From HI Dwarfs to Giants

    NASA Astrophysics Data System (ADS)

    Huang, Shan

    2013-01-01

    Making use of HI 21 cm line measurements from the ALFALFA survey (α.40) and photometry from the SDSS and GALEX, we investigate the global scaling relations linking stars and gas for 9417 common galaxies (α.40-SDSS-GALEX). Stellar masses (M*) and SFRs are derived from fitting the UV-optical SEDs. 96% of the α.40-SDSS-GALEX galaxies belong to the blue cloud, with the average gas fraction MHI/M* > 1.5. A transition in star formation (SF) properties is found whereby below M* > 109.5M⊙, the slope of the SF sequence changes, the dispersion in the specific star formation rate (SSFR) distribution increases, and the star formation efficiency (SFE) mildly increases with M*. The evolutionary track in the SSFR-M* diagram, as well as that in the CMD, is linked to the HI content; below this transition mass, the SF is regulated strongly by the HI. Comparison of HI and optically selected samples shows that the HI-selected population is less evolved and has overall higher SFR and SSFR at a given M*, but lower SFE and extinction, suggesting either that a bottleneck exists in the HI-to-H2 conversion, or that the very HI-dominated galaxies obey an low efficiency SF law. We show that for a given M*, high gas fraction galaxies reside preferentially in dark matter halos with high spin parameters. In addition, we closely studied 229 low MHI ALFALFA dwarfs with reprocessed GALEX photometry. Many of them are currently undergoing active SF, relative to the past-averaged level, so that the widely used standard formulae calibrated for a continuous SF history systematically overestimate the M* and SFR. Currently, we are gathering multi-wavelength data for the High HI Mass, HI-rich (HIghMass) galaxies identified by the ALFALFA (MHI>1010M⊙ and gas fraction more than 1σ above the mean given their M*). They may be in an arrested stage of evolution, or their huge HI disks may reflect recent baryon accretion. Most of the HIghMass galaxies exhibit strong color gradient and have higher Hα EWs in the outer disks, i.e., SF is migrating outward. The spin parameters of the HIghMass galaxies are confirmed to be overall higher than the ALFALFA general population. This research is supported by NSF grants AST-0607007 AST-1107390 and by the Brinson Foundation.

  4. [POLYMORPHISM OF ALFA-AMYLASE AND CONJUGATION IN COMMON WHEAT ENZYME TYPES WITH QUANTITATIVE TRAITS OF PLANTS].

    PubMed

    Netsvetaev, V P; Bondarenko, L S; Motorina, I P

    2015-01-01

    Using polymorphism of alpha-amylase in the winter common wheat studied inheritance isoenzymes and its conjugation enzyme types with germinating grain on the "vine", grain productivity, plant height and time of ear formation. It is shown that the polymorphism isoenzyme of alpha-amylase wheat is limited by the presence of different loci whose products are similar in electrophoretic parameters. In this regard, one component of the enzyme can be controlling at one or two or three genes. Identification of a locus controlling alpha-amylase isoenzyme in the fast moving part of the electrophoretogram, designated as α-Amy-B7. Determine the distance of the locus to factor α-Amy-B6. PMID:26841490

  5. CONSORT: Effects of adding adefovirdipivoxil to peginterferon alfa-2a at different time points on HBeAg-positivepatients

    PubMed Central

    Zhang, Ka; Cao, Hong; Liang, Jiayi; Shu, Xin; Sun, Haixia; Li, Gang; Xu, Qihuan

    2016-01-01

    Abstract Background: The aims of this study were to compare the efficacy and safety of the addition of adefovir dipivoxil (ADV) (started at different time points) to pegylated interferon alpha-2a (PEG-INF-α2a) and PEG-INF-α2a monotherapy. This prospective, randomized study sought to evaluate the safety and efficacy of the combination of PEG-INF-α2a and ADV at different time points.120 patients were randomized into groups that received PEG-INF-α2a as monotherapy (group A) or in combination with ADV started at week 0 (group B), 12 (group C), or 24 (group D). All patients were followed for 48 weeks. Efficacy and safety analyses were performed. Methods: Patients in group a received 135 μg of PEG-INF-α2a by subcutaneous injection once weekly for 48 weeks. Patients in the ADV add-on group received 135 μg of PEG-INF-α2a subcutaneously once weekly and received 10 mg of ADV administered once daily for 48 weeks. HBV DNA, HBsAg, HBeAg, and hepatitis B e antibody levels were determined. Responses were determined at week 12 (ADV add-on), the end of treatment for PEG-INF-α2a (48weeks) and ADV (EOT) and at the end of 96 weeks of follow-up (EOF). Results: The rate of HBV DNA loss were higher in the combination groups than group A at the week 12, week 48, the EOT and EOF (P < 0.05). The rates of HBeAg seroconversion and HBsAg loss were similar among the treatment groups (P>0.05). The alanineaminotransferase (ALT) normalization rate was higher in the combination group than group A only at the EOT (P = 0.007). By the EOF, the patients with ADV added at week 12 achieved higher rates of HBV DNA loss (71.9%), HBeAg seroconversion (50.0%), HBsAg loss (15.6%), and ALT normalization (78.1%). Conclusions: PEG-INF-α2a plus ADV combination therapy is safe and superior to PEG-INF-α2amonotherapyfor decreasing serum HBV DNA and normalizing the ALT level but has no significant impact on the rate of HBeAg seroconversion and HBsAg loss. Adding ADV at week 12 may be an optimal combination strategy. PMID:27495085

  6. Sciami meteorici minori d'Agosto: le Piscis Austrinidi, le alfa Capricornidi e le delta Acquaridi meridionali

    NASA Astrophysics Data System (ADS)

    Sigismondi, Costantino

    2016-09-01

    The Piscis Austrinids, PAU, Alpha Capricornids CAP, and Southern Delta Acquarids SDA meteors are minor shower during the month of August, occurring during the most famous Perseids shower. These rare meteors are 'fossil' of their parent body (comet or asteroid) already destroyed since several thousands of years. Useful observations can give information on their dynamics and density.

  7. Pharmacologic management of overactive bladder.

    PubMed

    Lam, Sum; Hilas, Olga

    2007-01-01

    Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.

  8. Functional selectivity of muscarinic receptor antagonists for inhibition of M3-mediated phosphoinositide responses in guinea pig urinary bladder and submandibular salivary gland.

    PubMed

    Nelson, Carl P; Gupta, Paul; Napier, Carolyn M; Nahorski, Stefan R; Challiss, R A John

    2004-09-01

    Binding and functional affinities of the muscarinic acetylcholine (mACh) receptor antagonists darifenacin, tolterodine, oxybutynin, and atropine were assessed in Chinese hamster ovary (CHO) cells expressing the human recombinant M2 (CHO-m2) or M3 (CHO-m3) receptors, and in guinea pig bladder and submandibular gland. In [N-methyl-3H]scopolamine methyl chloride binding studies in CHO cells, darifenacin displayed selectivity (14.8-fold) for the M3 versus M2 mACh receptor subtype. Oxybutynin was nonselective, whereas atropine and tolterodine were weakly M2-selective (5.1- and 6.6-fold, respectively). Antagonist functional affinity estimates were determined by the inhibition of agonist-induced [3H]inositol phosphate accumulation in CHO-m3 cells and antagonism of the agonist-induced inhibition of forskolin-stimulated cyclic AMP accumulation in CHO-m2 cells. Darifenacin was the most M3-selective antagonist (32.4-fold), whereas oxybutynin, atropine, and tolterodine exhibited lesser selectivity. Functional affinity estimates in guinea pig urinary bladder and submandibular salivary gland using indices of phosphoinositide turnover revealed that oxybutynin, darifenacin, and tolterodine each displayed selectivity for the response in the bladder, relative to that seen in the submandibular gland (9.3-, 7.9-, and 7.4-fold, respectively). In contrast, atropine displayed a similar affinity in both tissues. These data demonstrate that in bladder, compared with submandibular gland from a single species, the mACh receptor antagonists darifenacin, tolterodine, and oxybutynin display selectivity to inhibit agonist-mediated phosphoinositide responses. It is proposed that both responses are mediated via M3 mACh receptor activation and that differential functional affinities displayed by some, but not all, antagonists are indicative of the influence of cell background upon the pharmacology of the M3 mACh receptor. PMID:15140916

  9. Comportamiento de la cromósfera solar en la línea H-alfa durante el período enero/05-agosto/06

    NASA Astrophysics Data System (ADS)

    Missio, H.; Davoli, D.; Aquilano, R.

    Using the instrument at Observatorio Astronómico Municipal de Rosario (OAMR), we analyze the solar chromospheric activity during the period January/05-August/06. The instrument is a Carl Zeiss refractor telescope of 150 mm aperture and 2250 mm of focal distance with a monochromatic filter in the H-alpha line. We take as proxy for the solar activity the area covered by chromospheric ``plages''. The measurements are done using photographic registers. We describe our technique and the results obtained. We observe a decrease of solar activity that corresponds to the end of cycle 23. FULL TEXT IN SPANISH

  10. Sialadenitis following low dose I-131 diagnostic thyroid scan with Thyrogen® (recombinant human thyroid stimulating hormone--thyrotropin alfa).

    PubMed

    Gonzalez, Marta E; Muttikkal, Thomas Jose Eluvathingal; Rehm, Patrice K

    2015-06-01

    Salivary dysfunction and sialadenitis are well known complications of radioiodine treatment for thyroid cancer. The parotid gland is more frequently affected and the salivary gland injury is dose related. The symptoms may develop shortly after therapeutic Iodine 131(I-131) administration or months later and progress with time. The development of unilateral parotiditis following a low dose, diagnostic I-131 scan performed following Thyrogen stimulation in a patient without prior history of sialadenitis is rare in our experience, and has not been reported in the medical literature.

  11. Effects of selective alfa 1 and beta 1-adrenoreceptor blockade on lipoprotein and carbohydrate metabolism in hypertensive subjects, with special emphasis on insulin sensitivity.

    PubMed

    Andersson, P E; Johansson, J; Berne, C; Lithell, H

    1994-03-01

    The central role of insulin resistance in patients with essential hypertension was the impetus for the present study, in which carbohydrate and lipid metabolism were examined before and after three months treatment with doxazosin (n = 14) and atenolol (n = 15). After completion of a randomised parallel group trial, the study was extended in a subgroup of the patients who continued treatment with doxazosin for a further nine months (n = 18). Insulin sensitivity was measured with the euglycemic hyperinsulinaemic clamp. Blood glucose and plasma insulin were analysed in the fasting state and during an intravenous glucose tolerance test (IVGTT). Lipoprotein fractions were analysed in serum. After three months, SBP and DBP in the standing position decreased to the same extent after the two drugs whereas the decrease in supine SBP did not reach statistical significance in the doxazosin group. Doxazosin, in contrast to atenolol, decreased serum triglycerides (-17%, P < 0.04) by lowering the VLDL and LDL fractions. Serum cholesterol fell after doxazosin (-7%, P < 0.02) but not after atenolol. The effects of doxazosin on serum lipids remained the same during the long-term follow-up. At three months neither drug had significantly affected variables reflecting insulin sensitivity although atenolol tended to decrease the insulin sensitivity index (-17%, P = 0.08). After 12 months the doxazosin group showed a significant increase in the insulin sensitivity index and a significant decrease in both basal plasma insulin and in the late insulin response at IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. THE ARECIBO LEGACY FAST ALFA SURVEY: THE {alpha}.40 H I SOURCE CATALOG, ITS CHARACTERISTICS AND THEIR IMPACT ON THE DERIVATION OF THE H I MASS FUNCTION

    SciTech Connect

    Haynes, Martha P.; Giovanelli, Riccardo; Martin, Ann M.; Adams, Elizabeth A. K.; Hallenbeck, Gregory; Huang Shan; Papastergis, Emmanouil E-mail: riccardo@astro.cornell.edu E-mail: betsey@astro.cornell.edu E-mail: shan@astro.cornell.edu; and others

    2011-11-15

    We present a current catalog of 21 cm H I line sources extracted from the Arecibo Legacy Fast Arecibo L-band Feed Array (ALFALFA) survey over {approx}2800 deg{sup 2} of sky: the {alpha}.40 catalog. Covering 40% of the final survey area, the {alpha}.40 catalog contains 15,855 sources in the regions 07{sup h}30{sup m} < R.A. < 16{sup h}30{sup m}, +04 Degree-Sign < decl. <+16 Degree-Sign , and +24 Degree-Sign < decl. <+28 Degree-Sign and 22{sup h} < R.A. < 03{sup h}, +14 Degree-Sign < decl. <+16 Degree-Sign , and +24 Degree-Sign < decl. < + 32 Degree-Sign . Of those, 15,041 are certainly extragalactic, yielding a source density of 5.3 galaxies per deg{sup 2}, a factor of 29 improvement over the catalog extracted from the H I Parkes All-Sky Survey. In addition to the source centroid positions, H I line flux densities, recessional velocities, and line widths, the catalog includes the coordinates of the most probable optical counterpart of each H I line detection, and a separate compilation provides a cross-match to identifications given in the photometric and spectroscopic catalogs associated with the Sloan Digital Sky Survey Data Release 7. Fewer than 2% of the extragalactic H I line sources cannot be identified with a feasible optical counterpart; some of those may be rare OH megamasers at 0.16 < z < 0.25. A detailed analysis is presented of the completeness, width-dependent sensitivity function and bias inherent of the {alpha}.40 catalog. The impact of survey selection, distance errors, current volume coverage, and local large-scale structure on the derivation of the H I mass function is assessed. While {alpha}.40 does not yet provide a completely representative sampling of cosmological volume, derivations of the H I mass function using future data releases from ALFALFA will further improve both statistical and systematic uncertainties.

  13. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2016-11-03

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  14. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

    EPA Science Inventory

    Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF.
    Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson.
    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

  15. Concentration-guided ribavirin dosing with darbepoetin support and peg-IFN alfa-2a for treatment of hepatitis C recurrence after liver transplantation.

    PubMed

    Ackefors, M; Gjertsen, H; Wernerson, A; Weiland, O

    2012-09-01

    Relapse of hepatitis C virus infection after liver transplantation is universal. Standard-of-care (SOC) treatment for relapse offers less satisfactory treatment response than in nontransplanted patients. Tolerance for treatment is suboptimal and withdrawals owing to adverse events induced by treatment frequent. To improve tolerance for SOC, and ribavirin (RBV) in particular, concentration-guided RBV dosing calculated by a formula taking renal function and weight into consideration was utilized. A serum RBV concentration of 10 μm was set as the goal. All patients were given maintenance darbepoetin therapy from 2 weeks prior to initiation of treatment. In total, 21 patients with a mean age of 52 (range 25-64) years were included. The mean RBV concentration at week 4 was 10.2 and 7.36 μm in genotype 1/4 and non-1/4 patients, respectively, and 11.7 and 9.42 at week 12. The mean haemoglobin drop was 25 g/L vs 21 g/L in the genotype 1/4 and non-1/4 group, respectively, a nonsignificant difference. With this treatment approach, 80-90% of patients could be kept adherent to treatment. Sustained viral response was achieved 8/16 (50%) with low-grade fibrosis (fibrosis stage ≤ 2) vs in none of five patients with advanced fibrosis (Fibrosis stage 3 and 4), P < 0.05. We conclude that a treatment algorithm utilizing concentration-guided RBV dosing during darbepoetin maintenance therapy substantially improves tolerance and allows high adherence to a SOC treatment schedule, and that therapy needs to be initiated before advanced fibrosis is developed. PMID:22863267

  16. Levels of Salivary IFN-gamma, TNF-Alfa, and TNF Receptor-2 As Prognostic Markers in (Erosive) Oral Lichen Planus

    PubMed Central

    Ghallab, Noha A.; El-Wakeel, Naglaa; Shaker, Olfat G.

    2010-01-01

    To explore the feasibility of detecting salivary levels of IFN-γ, TNF-α, and sTNFR-2 from erosive oral lichen planus (ELP) patients for clinical application, 20 ELP patients were enrolled in the study as were 20 age-sex-matched controls. From all subjects, saliva level of the tested biomarkers was determined by ELISA. Salivary profiles were assessed in ELP patients by ELISA after being treated with prednisone. A significantly higher level of IFN-γ (P ≤ .01), TNF-α (P ≤ .0001), and sTNFR-2 (P ≤ .01) was detected in ELP patients before treatment than in controls. Following treatment, the salivary levels of IFN-γ (P ≤ .01), TNF-α (P ≤ .05), and sTNFR-2 (P ≤ .01) decreased significantly when compared to their pretreatment levels. This study demonstrated that salivary IFN-γ, TNF-α, and sTNFR-2 can be detectable in ELP patients and decreased significantly after treatment with prednisone, which may reveal the possibility of using these disease-related biomarkers in diagnosis and monitoring. PMID:21403886

  17. Identification and characterization of isomeric N-glycans of human alfa-acid-glycoprotein by stable isotope labelling and ZIC-HILIC-MS in combination with exoglycosidase digestion.

    PubMed

    Mancera-Arteu, Montserrat; Giménez, Estela; Barbosa, José; Sanz-Nebot, Victòria

    2016-10-12

    In this study, a ZIC-HILIC-MS methodology for the analysis of N-glycan isomers was optimized to obtain greater detection sensitivity and thus identify more glycan structures in hAGP. In a second step, this method was combined with glycan reductive isotope labelling (GRIL) through [(12)C6]/[(13)C6]-aniline and exoglycosidase digestion to characterize the different glycan isomers. The GRIL method allows the peak areas resulting from two different labelled samples to be compared, since neither retention time shifts nor variations in the ionization of glycans between these samples are obtained. First, sialic acid linkage assignations were performed for most hAGP glycan isomers with α2-3 sialidase digestion. Bi-, tri- and tetraantennary glycan isomers with different terminal sialic acid linkages to galactose (α2-3 or α2-6) were assigned, and the potential of this technique for the structural characterization of isobaric isomers was therefore demonstrated. Furthermore, fucose linkage isomers of hAGP glycans were also characterized using this isotope-labelling approach in combination with α1-3,4 fucosidase and β1-4 galactosidase digestion. α1-3 antennary fucoses and α1-6 core fucosylation were detected in hAGP fucosylated glycans. These established methodologies can be extremely useful for patho-glycomic studies to characterize glycoproteins of biomedical interest and find novel glycan isomers that could be used as biomarkers in cancer research. PMID:27662763

  18. Chemotherapy with DMXAA (5,6-dimethylxanthenone-4-acetic acid) in combination with CI-1010 (1H-imidazole-1-ethanol,alpha-[[(2-bromoethyl)amino]methyl]-2-nitro-,mon o-hydrobromide (R isomer)) against advanced stage murine colon carcinoma 26.

    PubMed

    Vincent, P; Roberts, B; Elliott, W; Leopold, W

    1997-01-01

    Because an enhanced therapeutic gain might be expected with co-administration of a hypoxic cell selective cytotoxin and a compound that induces hemorrhagic necrosis in tumors, the combination of CI-1010 (a potent bioreductive hypoxia selective cyto toxin) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) has been evaluated against advanced stage (>150 mg) murine colon carcinoma 26 (C26). CI-1010 and DMXAA were administered intraperitoneally over a range of toxic to ineffective doses as single agents and in combination to adult BALB/c x DBA/2 F1 hybrid mice bearing s.c. implants of C26. Both CI-1010 and DMXAA were ineffective as single agents, but regimens combining these two agents were highly active. The administration of DMXAA at 20 mg/kg/inj on days 9, 13, and 17 and CI-1010 at 65 mg/kg/inj on days 9-17 resulted in 60% of the animals tumor free on day 92 of the study. The remaining animals that were not tumor free survivors achieved a delay in tumor growth of 22.4 days. However, this treatment regimen was also considered toxic resulting in 2/10 treatment related deaths. Modification of the CI-1010 treatment schedule to intermittent delivery 24 h after each scheduled dose of DMXAA reduced treatment related toxicity while retaining efficacy. On this schedule the combination of CI-1010 (95 mg/kg/inj) given 24 h after DMXAA (20 mg/kg/inj) on days 9, 13, and 17 resulted in 60% of the treated animals tumor free on day 98 of the study. Treatment failures experienced a tumor growth delay of 11.6 days. Combination chemotherapy with CI-1010 and DMXAA was ineffective when DMXAA was administered 1 h prior to CI-1010, simultaneously with CI-1010, or 1 h after the administration of CI-1010. These results suggest that an enhanced therapeutic interaction between CI-1010 and DMXAA is achievable in vivo and that this interaction requires the development of substantial DMXAA induced tumor hypoxia prior to administration of CI-1010.

  19. Terahertz and Raman spectra of non-centrosymmetrical organic molecular crystals

    NASA Astrophysics Data System (ADS)

    Trzebiatowska-Gusowska, Monika; Plinski, Edward F.; Baran, Jan; Walczakowski, Michal J.; Jarzab, Przemyslaw P.; Nowak, Kacper; Fuglewicz, Boguslaw; Mikulics, Martin; Palka, Norbert; Szustakowski, Mieczyslaw

    2014-11-01

    The terahertz waves have been applied to the spectroscopy of molecular crystals. The group based on hybrid organic-inorganic crystals like triglycine zinc chloride, triglycine sulphate, triglycine selenate, diglycine hydrobromide, diglycine hydrochloride, diglycine lithium nitrate, glycine lithium nitrate has been considered. The dispersion relation phonon-polariton have been shown between 10 cm-1 and 80 cm-1 for diglycine lithium nitrate, triglycine zinc chloride, and diglycine hydrobromide.

  20. Discovery of FDA-approved drugs as inhibitors of fatty acid binding protein 4 using molecular docking screening.

    PubMed

    Wang, Yan; Law, Wai-Kit; Hu, Jian-Shu; Lin, Huang-Quan; Ip, Tsz-Ming; Wan, David Chi-Cheong

    2014-11-24

    We first identified fluorescein, ketazolam, antrafenine, darifenacin, fosaprepitant, paliperidone, risperidone, pimozide, trovafloxacin, and levofloxacin as inhibitors of fatty acid binding protein 4 using molecular docking screening from FDA-approved drugs. Subsequently, the biochemical characterizations showed that levofloxacin directly inhibited FABP4 activity in both the in vitro ligand displacement assay and cell-based function assay. Furthermore, levofloxacin did not induce adipogenesis in adipocytes, which is the major adverse effect of FABP4 inhibitors.

  1. Marketing scam spoils hep C treatment.

    PubMed

    1998-12-01

    Tandem packaging of the drugs Ribavirin (Rebetol) and interferon-alfa (Intron A), used to treat hepatitis C, limits patients' choice of which brand of interferon-alfa they can select. Marketed collectively as Rebetron, by their sponsor Schering-Plough, this combination is expensive and may restrict reimbursement from third party insurers if an alternate brand of interferon-alfa is needed. Currently, Ribavirin, which is more effective with interferon-alfa, is only available in this pairing.

  2. 49 CFR Appendix A to Part 593 - List of Vehicles Determined To Be Eligible for Importation

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 76 Alfa Romeo 164 1994 156 Alfa Romeo Spider 1987 70 Alfa Romeo Spyder 1992 503 Alpina B12 5.0 Sedan...-2000 327 Ferrari 360 Series 2004 446 Ferrari 360 Spider & Coupe 2003 410 Ferrari 456 GT & GTA 1999...

  3. Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system.

    PubMed

    Fong Yen, Woo; Basri, Mahiran; Ahmad, Mansor; Ismail, Maznah

    2015-01-01

    Galantamine hydrobromide is formulated in tablets and capsules prescribed through oral delivery for the treatment of Alzheimer's disease. However, oral delivery of drugs can cause severe side effects such as nausea, vomiting, and gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide could avoid these unwanted side effects. In this work, galantamine hydrobromide was formulated in gel drug reservoir which was then fabricated in the transdermal patch. The in vitro drug release studies revealed that the drug release from the donor chamber to receptor chamber of Franz diffusion cell was affected by the amount of polymer, amount of neutralizer, amount of drug, types of permeation enhancer, and amount of permeation enhancer. Visual observations of the gels showed that all formulated gels are translucent, homogeneous, smooth, and stable. These gels have pH in the suitable range for skin. The gel also showed high drug content uniformity. Hence, this formulation can be further used in the preparation of transdermal patch drug delivery system. PMID:25853145

  4. Analysis of Dextromethorphan in Cough Drops and Syrups: A Medicinal Chemistry Laboratory

    ERIC Educational Resources Information Center

    Hamilton, Todd M.; Wiseman, Frank L., Jr.

    2009-01-01

    Fluorescence spectroscopy is used to determine the quantity of dextromethorphan hydrobromide (DM) in over-the-counter (OTC) cough drops and syrups. This experiment is appropriate for an undergraduate medicinal chemistry laboratory course when studying OTC medicines and active ingredients. Students prepare the cough drops and syrups for analysis,…

  5. Coulometric determination of some antiasthmatics.

    PubMed

    Nikolic, K; Arsenijevec, L; Bogavac, M

    1993-03-01

    A simple and rapid method for the assay of microquantities of fenoterol hydrobromide, orciprenaline sulphate and terbutaline sulphate in pure state and various pharmaceutical formulations, is presented. The method is based on the coulometric titration of the investigated compounds with electrogenerated chlorine in the presence of methyl orange as indicator. The method requires a simple apparatus and gives accurate and reproducible results. PMID:8518319

  6. Galantamine-loaded solid-lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations.

    PubMed

    Misra, Shubham; Chopra, Kanwaljit; Sinha, V R; Medhi, Bikash

    2016-05-01

    Galantamine hydrobromide, a promising acetylcholinesterase inhibitor is reported to be associated with cholinergic side effects. Its poor brain penetration results in lower bioavailability to the target site. With an aim to overcome these limitations, solid-lipid nanoparticulate formulation of galantamine hydrobromide was developed employing biodegradable and biocompatible components. The selected galantamine hydrobromide-loaded solid-lipid nanoparticles offered nanocolloidal with size lower than 100 nm and maximum drug entrapment 83.42 ± 0.63%. In vitro drug release from these spherical drug-loaded nanoparticles was observed to be greater than 90% for a period of 24 h in controlled manner. In vivo evaluations demonstrated significant memory restoration capability in cognitive deficit rats in comparison with naive drug. The developed carriers offered approximately twice bioavailability to that of plain drug. Hence, the galantamine hydrobromide-loaded solid-lipid nanoparticles can be a promising vehicle for safe and effective delivery especially in disease like Alzheimer's. PMID:26405825

  7. Production of interferon in respiratory syncytial virus bronchiolitis.

    PubMed Central

    Isaacs, D

    1989-01-01

    Production of interferon alfa in vitro was significantly reduced during acute respiratory syncytial virus bronchiolitis but subsequently returned to normal. Nasopharyngeal and endotracheal interferon alfa were detected intermittently and in low concentrations. The degree of impairment of in vitro production and poor in vivo production of interferon alfa suggest the need for a therapeutic trial of nebulised or systemic interferon in acute bronchiolitis. PMID:2923479

  8. Free-surface phenomena under low- and zero-gravity conditions

    NASA Technical Reports Server (NTRS)

    Coles, D.

    1985-01-01

    An apparatus to measure contact angle was constructed to exploit the proposed internal-corner criterion. If 2 alfa is the internal angle between two intersecting vertical planes and gamma is the contact angle, a meniscus at the corner rises to a finite height if alfa + gamma pi/2 and to an infinite height if alfa + gamma pi/2. The apparatus operates by decreasing the angle alfa from pi/2 until the meniscus height changes abruptly. A number of liquids are tested on glass and plexiglas.

  9. 49 CFR Appendix A to Part 593 - List of Vehicles Determined To Be Eligible for Importation

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 1994 156 Alfa Romeo Spider 1987 70 Alfa Romeo Spyder 1992 503 Alpina B12 5.0 Sedan 1988-1994 41 Alpina... Series 2004 446 Ferrari 360 Spider & Coupe 2003 410 Ferrari 456 GT & GTA 1999 445 Ferrari 456 GT &...

  10. Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes

    EPA Science Inventory

    Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes Nanoparticle uptake in cells may be an important determinant of their potential cytotoxic and inflammatory effects. Six commercial TiO2 NP (A=Alfa Aesar,10nm, A*=Alfa Aesar 32nm, B=P25 27...

  11. Rapid and high-precision measurement of sulfur isotope and sulfur concentration in sediment pore water by multi-collector inductively coupled plasma mass spectrometry.

    PubMed

    Bian, Xiao-Peng; Yang, Tao; Lin, An-Jun; Jiang, Shao-Yong

    2015-01-01

    We have developed a technique for the rapid, precise and accurate determination of sulfur isotopes (δ(34)S) by MC-ICP-MS applicable to a range of sulfur-bearing solutions of different sulfur content. The 10 ppm Alfa-S solution (ammonium sulfate solution, working standard of the lab of the authors) was used to bracket other Alfa-S solutions of different concentrations and the measured δ(34)SV-CDT values of Alfa-S solutions deviate from the reference value to varying degrees (concentration effect). The stability of concentration effect has been verified and a correction curve has been constructed based on Alfa-S solutions to correct measured δ(34)SV-CDT values. The curve has been applied to AS solutions (dissolved ammonium sulfate from the lab of the authors) and pore water samples successfully, validating the reliability of our analytical method. This method also enables us to measure the sulfur concentration simultaneously when analyzing the sulfur isotope composition. There is a strong linear correlation (R(2)>0.999) between the sulfur concentrations and the intensity ratios of samples and the standard. We have constructed a regression curve based on Alfa-S solutions and this curve has been successfully used to determine sulfur concentrations of AS solutions and pore water samples. The analytical technique presented here enable rapid, precise and accurate S isotope measurement for a wide range of sulfur-bearing solutions - in particular for pore water samples with complex matrix and varying sulfur concentrations. Also, simultaneous measurement of sulfur concentrations is available.

  12. Quantization of Dextromethorphan and Levocetirizine in Combined Dosage form Using a Novel Validated RP-HPLC Method.

    PubMed

    Joshi, Shalini; Bhatia, C; Bal, C S; Rawat, M S M

    2012-01-01

    The present study reveals a simple isocratic RP-HPLC method for the simultaneous determination of dextromethorphan hydrobromide and levocetirizine dihydrochloride in a cough syrup. The separation of these compounds was achieved within 10 min on a Phenomenex (USA) C(18) analytical column, 250×4.0 mm i.d., using an isocratic mobile phase consisting of potassium dihydrogen phosphate buffer (pH 2.5) - acetonitrile- tetrahydrofuran (70:25:5, v/v/v). The analysis was performed at a flow rate of 1.2 ml/min and at a detection wavelength of 232 nm. Percentage recovery and RSD were 100.36% and 0.05% for levocetirizine dihydrochloride, 100.35% and 0.27% for dextromethorphan hydrobromide respectively. Quantification of the components in syrup formulation was calculated against the peak areas of freshly prepared standard solutions. The method was validated as per ICH guidelines. PMID:23204629

  13. Airborne testing of three antimotion sickness preparations

    NASA Technical Reports Server (NTRS)

    Johnson, W. H.; Money, K. E.; Graybiel, A.

    1976-01-01

    Thirteen human volunteers were exposed to weekly flights in which standardized, steep turns were used to produce motion sickness. A combination of promethazine hydrochloride (25 mg) plus ephedrine sulphate (25 mg) was found to be equally as effective as the combination of 1-scopolamine hydrobromide (0.35 mg) plus d-amphetamine sulphate (5 mg). Droperidol (2.5 mg) was indistinguishable from the placebo. It was concluded that the treatment of choice for motion sickness is promethazine plus ephedrine.

  14. Approaches to interferon combination therapy in the treatment of AIDS.

    PubMed

    Krown, S E

    1990-02-01

    High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units or more per day are used to induce responses, constitutional and hematologic side effects may be significant. Therefore, efforts are being made to lower the effective dose of IFN alfa. One effort involves combining IFN alfa with zidovudine (AZT; Retrovir; Burroughs Wellcome, Research Triangle Park, NC). These agents act synergistically to block the multiplication of human immunodeficiency virus (HIV) in vitro. The drugs act at different points in the HIV multiplication cycle, which may explain their synergistic interaction. In addition, AZT enhances certain immune functions that have been correlated with a positive IFN alfa response. Preliminary clinical trials indicate that antitumor responses in Kaposi's sarcoma are seen with dosages of IFN alfa as low as 4.5 x 10(6) units per day when combined with AZT. However, the combination of IFN alfa and AZT may also produce dose-limiting hematologic side effects; these effects may limit the usefulness of the drug combination. Strategies for ameliorating these toxicities through the use of additional agents are discussed.

  15. [Oral anticholinergics in overactive bladder].

    PubMed

    Madersbacher, H

    2006-07-01

    Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the "newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects.

  16. Myeloprolipherative disorder type chronic myeloid leukemia--eosinophilic form.

    PubMed

    Arnautovic-Custovic, Aida; Hasic, Samira; Kopic, Emina; Jahic, Azra; Jovic, Svetlana

    2011-01-01

    Chronic eosinophilic leukemia (CEL) is a very rare form of leucemia in the western world. Adequate response is seldomly achieved after treatment with corticosteroids, interferon-alfa (INF-alfa) and medications containing hydroxi-urea (Litalir). The study presents a patient with CEL with no initial therapeutic response to the use of corticosteroids, INF-alfa and hydroxy-urea, and with neither clinical nor hematological response. After setting a diagnosis of CEL, patient was ordinated Imatinib (Glivec tabbletes) in a daily dose of 200 mg. Two days afterwards there was an evident withdrawal of subjective and clinical symptoms of disease, and the complete blood count showed significant amendment.

  17. [Intragenic deletions of NRXN1: three new case reports and a review of the phenotype].

    PubMed

    Galán-Sánchez, Francisco; Esteban-Cantó, Vanessa; Blaya-Fernández, Pedro; Jadraque-Rodríguez, Rocío; Manchón-Trives, Irene; Alcaraz-Más, Luis

    2015-03-01

    Objetivo. Aportar datos sobre el fenotipo determinado por las microdeleciones de los exones alfa del gen NRXN1. Casos clinicos. Se estudian tres casos neuropediatricos con microdeleciones intragenicas NRXN1 alfa. El fenotipo en estos tres casos es inespecifico, con retraso mental leve-moderado, trastornos de comportamiento y escasos rasgos dismorficos o malformaciones. Conclusion. El fenotipo encontrado en las microdeleciones de los exones alfa del gen NRXN1 es claramente distinguible del fenotipo encontrado en las microdeleciones de los exones beta, con macrocefalia, epilepsia y retraso mental.

  18. Myeloprolipherative disorder type chronic myeloid leukemia--eosinophilic form.

    PubMed

    Arnautovic-Custovic, Aida; Hasic, Samira; Kopic, Emina; Jahic, Azra; Jovic, Svetlana

    2011-01-01

    Chronic eosinophilic leukemia (CEL) is a very rare form of leucemia in the western world. Adequate response is seldomly achieved after treatment with corticosteroids, interferon-alfa (INF-alfa) and medications containing hydroxi-urea (Litalir). The study presents a patient with CEL with no initial therapeutic response to the use of corticosteroids, INF-alfa and hydroxy-urea, and with neither clinical nor hematological response. After setting a diagnosis of CEL, patient was ordinated Imatinib (Glivec tabbletes) in a daily dose of 200 mg. Two days afterwards there was an evident withdrawal of subjective and clinical symptoms of disease, and the complete blood count showed significant amendment. PMID:21776882

  19. Training Strategy: Computer Education for Teachers in Uruguay.

    ERIC Educational Resources Information Center

    Grunberg, Jorge

    1987-01-01

    Described is the Alfa Project in Uruguay, designed to integrate computer education into secondary schools through teacher-training. Both teacher-users and teacher-authors were considered. Course objectives, curriculum content, and teaching guidelines are presented. (MNS)

  20. 32. VIEW LOOKING INSIDE 'BRAVO' SILO. GRAFFITI IS YELLOWCOLORED LION, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. VIEW LOOKING INSIDE 'BRAVO' SILO. GRAFFITI IS YELLOW-COLORED LION, SAME AS IN 'ALFA' Marilyn Ziemer, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

  1. Simeprevir

    MedlinePlus

    ... Rebetol) and peginterferon alfa (Pegasys) to treat chronic hepatitis C (an ongoing viral infection that damages the liver). ... inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. Simeprevir may not ...

  2. AIDSinfo Drug Database

    MedlinePlus

    ... B Virus Infection Hepatitis A and Hepatitis B (Recombinant) Vaccine Hepatitis B Vaccine Peginterferon Alfa-2a (HBV, HCV) ... 11, 16, 18, 31, 33, 45, 52, 58) Vaccine, Recombinant Human Papillomavirus Bivalent (types 16 and 18) Vaccine, ...

  3. 49 CFR Appendix A to Part 593 - List of Vehicles Determined To Be Eligible for Importation

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 156 Alfa Romeo Spider 1992 503 Alpina B11 Sedan 1989-1994 48 Alpina B12 Coupe 1989-1996 43 Alpina B12... 161 Ferrari 360 2001 376 Ferrari 360 Spider & Coupe 2003 410 Ferrari 360 (manufactured after...

  4. A new recombinant factor VIII: from genetics to clinical use

    PubMed Central

    Santagostino, Elena

    2014-01-01

    Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII) are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A. PMID:25548513

  5. Effects of different crops and soil managements on runoff for hillslopes

    NASA Astrophysics Data System (ADS)

    Ventura, F.; Pieri, L.; Gaspari, N.; Rossi Pisa, P.

    2003-04-01

    Runoff and soil erosion are natural phenomena strongly influenced by agricultural activities. Their main consequences are soil degradation, declining soil fertility, limiting infiltration capacity and water storage and have a strong negative feed-back on agriculture. Runoff prevention and soil conservation on agricultural land have also beneficial effects in reducing flood risk, especially against a background of climate change. In order to limit soil degradation a deep knowledge of all the factors taking part in the runoff process is necessary due to the fact that it occurs under very diverse conditions, depending on interactions between land use, climate, soils and topography. In particular in this study we have focalised our attention on two aspects: firstly we compared various use of agricultural soil, choosing between the most common crops of our region; secondly we studied different hydrological management in order to control the soil loss. The trial was carried out in Ozzano (Bo), Italy, (44^o25'N, 11^o28'E, 200 m a.s.l.) in plots with different slopes (from 0.65% to 17,9%) and tillage directions. Selected crops were wheat, sorghum and alfa alfa, whose rotation allowed the study of increasing vegetation densities, from bare soil, during the wheat-sorghum season, to the alfa alfa complete coverage. In addition we considered also a plot with cherry wood trees situated by the trial site. We examined five years of data with the aim of underlining relationships among vegetation density, plot slope, runoff and rainfall quantity - intensity - erosivity. The first findings show that: the values of runoff in alfa alfa are one order of magnitude lower than in sorghum and wheat, even with high erosive rainfall events. Cherry wood trees covered soil yields runoff amount lower than alfa alfa, since leaves interception of rain drops and the presence of brushwood retard the runoff, confirming the importance of forest cover to limit erosion processes.

  6. Characterization of gene-activated human acid-β-glucosidase: Crystal structure, glycan composition, and internalization into macrophages

    PubMed Central

    Brumshtein, Boris; Salinas, Paul; Peterson, Brian; Chan, Victor; Silman, Israel; Sussman, Joel L; Savickas, Philip J; Robinson, Gregory S; Futerman, Anthony H

    2010-01-01

    Gaucher disease, the most common lysosomal storage disease, can be treated with enzyme replacement therapy (ERT), in which defective acid-β-glucosidase (GlcCerase) is supplemented by a recombinant, active enzyme. The X-ray structures of recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme®) and in transgenic carrot cells (prGCD) have been previously solved. We now describe the structure and characteristics of a novel form of GlcCerase under investigation for the treatment of Gaucher disease, Gene-ActivatedTM human GlcCerase (velaglucerase alfa). In contrast to imiglucerase and prGCD, velaglucerase alfa contains the native human enzyme sequence. All three GlcCerases consist of three domains, with the active site located in domain III. The distances between the carboxylic oxygens of the catalytic residues, E340 and E235, are consistent with distances proposed for acid–base hydrolysis. Kinetic parameters (Km and Vmax) of velaglucerase alfa and imiglucerase, as well as their specific activities, are similar. However, analysis of glycosylation patterns shows that velaglucerase alfa displays distinctly different structures from imiglucerase and prGCD. The predominant glycan on velaglucerase alfa is a high-mannose type, with nine mannose units, while imiglucerase contains a chitobiose tri-mannosyl core glycan with fucosylation. These differences in glycosylation affect cellular internalization; the rate of velaglucerase alfa internalization into human macrophages is at least 2-fold greater than that of imiglucerase. PMID:19741058

  7. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

    Abacavir sulfate/lamivudine, Adalimumab, AdCD40L, Adefovir, Adefovir dipivoxil, Ambrisentan, Amlodipine, Amlodipine besylate/olmesartan medoxomil, AN-2728, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride, Atrasentan, Azacitidine, Bevacizumab, Blinatumomab, Bortezomib, Bosentan, Carfilzomib, Caspofungin acetate, Cediranib, Cetuximab, Choriogonadotropin alfa, Clevudine, Clindamycin phosphate/benzoyl peroxide, Clofarabine, Daidzeol, Darunavir, Dasatinib, Decitabine, Deferasirox, Deforolimus, Degarelix acetate, Denenicokin, Dexlansoprazole, Duloxetine hydrochloride, Elacytarabine, Enfuvirtide, Enoxaparin, Entecavir, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Ezetimibe/simvastatin, Forodesine hydrochloride, Fosamprenavir calcium, Gefitinib, Gemtuzumab ozogamicin, Golimumab, Imatinib mesylate, Imetelstat, Insulin gl'argine, Insulin glulisine, Interferon alfa-2b XL, Ivabradine hydrochloride, Lacosamide, Lenalidomide, Lintuzumab, Liposomal adriamycin, Liposomal belotecan, Liposome-encapsulated fentanyl, Lopinavir/ritonavir, Lutropin alfa, LY-207320, Maraviroc, Mecasermin, MKC-253, MP-470, NGR-TNF, Nilotinib hydrochloride monohydrate, Ofatumumab, Olmesartan medoxomil, Omacetaxine mepesuccinate, PAN-811, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perospirone hydrochloride, PF-734200, Phentermine/topiramate, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Pregabalin, Raltegravir potassium, Ramelteon, Ranibizumab, Recombinant Bet V1, Recombinant human insulin, Regadenoson, rhITF, Romidepsin, Rosuvastatin calcium, Ruboxistaurin hydrochloride, Rufinamide, Sapropterin dihydrochloride Saracatinib, SB-73, SC-599, Seliciclib, Sirolimus-eluting stent, Sorafenib, Sunitinib malate, Tadalafil, Tanespimycin, Tapentadol hydrochloride, Tegaserod maleate, Telbivudine, Tenofovir

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  9. The effects of scopolamine on extinction and spontaneous recovery.

    PubMed

    Morley, B J; Russin, R

    1978-04-11

    The effects of scopolamine hydrobromide on baseline extinction levels and spontaneous recovery were assessed. Rats were trained on one of four reinforcement schedules (CRF, FR 10, FR 20, FR 40) with either food or water reinforcement. Scopolamine increased response rates in extinction and spontaneous recovery following training on all four schedules when the reinforcer was water, but had no effect on responding previously maintained by food. The results are discussed in terms of the limitations of a general theory of a cholinergic system mediating all suppressed behavior and the effects of anticholinergic drugs on central thirst mechanisms and consummatory behavior.

  10. LC for analysis of two sustained-release mixtures containing cough cold suppressant drugs.

    PubMed

    El-Gindy, Alaa; Sallam, Shehab; Abdel-Salam, Randa A

    2010-07-01

    A liquid chromatographic method was applied for the analysis of two sustained-release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used for their simultaneous determination using a CN column with a mobile phase consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH 6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2. PMID:20822669

  11. Alternative to Ph. Eur. pour-plate method for detection of microbial contamination in non-sterile pharmaceutical preparations.

    PubMed

    Palicz, A; Paul, A; Hofmann, A; Denzel, K

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  12. Matching-adjusted indirect comparisons of efficacy of BAY 81-8973 vs two recombinant factor VIII for the prophylactic treatment of severe hemophilia A

    PubMed Central

    Pocoski, Jennifer; Li, Nanxin; Ayyagari, Rajeev; Church, Nikki; Maas Enriquez, Monika; Xiang, Quer; Kelkar, Sneha; Du, Ella X; Wu, Eric Q; Xie, Jipan

    2016-01-01

    Background No head-to-head trials comparing recombinant factor VIII (rFVIII) products currently exist. This was a matching-adjusted indirect comparison (MAIC) study of efficacy of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) and turoctocog alfa for the prophylaxis of severe hemophilia A. Methods A systematic literature review was conducted to identify trials of rAHF-PFM and turoctocog alfa. Comparisons were conducted using BAY 81-8973 individual patient data (IPD) from LEOPOLD trials and published data from rAHF-PFM and turoctocog alfa trials. Differences in outcome reporting were reconciled using transformation of BAY 81-8973 IPD. Patients in pooled LEOPOLD trials were weighted to match baseline characteristics for rAHF-PFM or turoctocog alfa trials using MAICs. After matching, annualized bleed rates (ABRs) were compared using weighted t-tests. Results Two rAHF-PFM trials and one turoctocog alfa trial were identified. In these trials, rFVIIIs were dosed thrice weekly or every other day; in LEOPOLD trials, BAY 81-8973 was dosed twice- or thrice weekly. Three MAICs were conducted because the two rAHF-PFM trials calculated ABRs differently, matching for age, race, and weight (turoctocog alfa only). BAY 81-8973 had similar ABR of all bleeds vs rAHF-PFM (two trials: 4.8 vs 6.3, 1.9 vs 1.8 [square root transform]) and lower ABR of spontaneous bleeds and trauma bleeds (2.6 vs 4.1, 2.1 vs 4.7; both P<0.05). BAY 81-8973 showed lower ABR of all bleeds and spontaneous bleeds vs turoctocog alfa (4.3 vs 6.5, 2.8 vs 4.3; both P<0.05) and similar ABR of trauma bleeds (1.5 vs 1.6). In subgroup analysis, twice-weekly BAY 81-8973 had similar ABRs of all bleeds, spontaneous bleeds, and trauma bleeds compared to rAHF-PFM and turoctocog alfa. Conclusion This indirect comparison found that prophylaxis with BAY 81-8973, even including the lower frequency of two times a week and lower factor VIII consumption, has efficacy comparable to r

  13. Alternative to Ph. Eur. pour-plate method for detection of microbial contamination in non-sterile pharmaceutical preparations.

    PubMed

    Palicz, A; Paul, A; Hofmann, A; Denzel, K

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  14. Updates from guardian™: a comprehensive registration programme.

    PubMed

    Ozelo, Margareth C

    2015-12-01

    Turoctocog alfa is an approved B-domain truncated recombinant factor VIII concentrate for adults and children with haemophilia A. Clinical data for turoctocog alfa have been reported from the guardian(™) 1, guardian(™) 2 and guardian(™) 3 phase III trials. guardian(™) 1 and guardian(™) 3 phase III trials enrolled 150 adolescents/adults (≥ 12 yr), and 63 children (<12 yr), respectively, with previously treated severe haemophilia A and no history of inhibitors; 188 of these patients continued into the ongoing guardian(™) 2 extension trial. In the three trials, patients have received prophylaxis with turoctocog alfa three times weekly or every second day, with breakthrough bleeds resolved to an expected postinjection level of ≥ 0.50 IU/mL. No safety concerns have arisen, and no patients have developed confirmed inhibitors (primary endpoint). Indeed, no confirmed inhibitors have been detected in >200 patients treated for a cumulative total of >54,000 exposure days in the phase III trials. Pooled efficacy data show a favourable long-term effect of turoctocog alfa on annualised bleeding rate and a success rate for haemostatic response of 86%; 90% of bleeds were resolved with 1-2 doses. This article reviews the clinical development of turoctocog alfa with reference to the guardian(™) clinical programme, describing results obtained to date and ongoing trials.

  15. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-05-01

    O(6)-Benzylguanine; (-)-Gossypol; Abatacept, AC-2592, Adalimumab, AIDSVAX gp120 B/E, Alemtuzumab, Aliskiren fumarate, ALVAC E120TMG, Ambrisentan, Amlodipine, Anakinra, Aripiprazole, Armodafinil, Atomoxetine hydrochloride, Avotermin; Bevacizumab, BIBW-2992, Bortezomib, Bosentan, Botulinum toxin type B; Canakinumab, CAT-354, Ciclesonide, CMV gB vaccine, Corifollitropin alfa, Daptomycin, Darbepoetin alfa, Dasatinib, Denosumab; EndoTAG-1, Eplerenone, Esomeprazole sodium, Eszopiclone, Etoricoxib, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; F-50040, Fesoterodine fumavate, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, Golimumab; Imatinib mesylate, Inhalable human insulin, Insulin glargine, Ivabradine hydrochloride; Lercanidipine hydrochloride/enalapril maleate, Levosimendan, Liposomal vincristine sulfate, Liraglutide; MDV-3100, Mometasone furoate/formoterol fumavate, Multiepitope CTL peptide vaccine, Mycophenolic acid sodium salt, Nabiximols, Natalizumab, Nesiritide; Obeticholic acid, Olmesartan medoxomil, Omalizumab, Omecamtiv mecarbil; Paclitaxel-eluting stent, Paliperidone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, Polymyxin B nonapeptide, PORxin-302, Prasugrel, Pregabalin, Pridopidine; Ranelic acid distrontium salt, Rasagiline mesilate, rDEN4delta30-4995, Recombinant human relaxin H2, rhFSH, Rilonacept, Rolofylline, Rosiglitazone maleate/metformin hydrochloride, Rosuvastatin calcium, Rotigotine; Salcaprozic acid sodium salt, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, Temsirolimus, Tenofovir, Tenofovir disoproxil fumarate, Teriparatide, Tiotropium bromide, Tocilizumab, Tolvaptan, Tozasertib, Treprostinil sodium; Ustekinumab; Vardenafil hydrochloride hydrate, Varenicline tartrate, Vatalanib succinate, Voriconazole, Vorinostat; Zotarolimus-eluting stent. PMID:20508873

  16. Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review.

    PubMed

    Toscano, Antonio; Schoser, Benedikt

    2013-04-01

    Glycogen storage disease type 2/Pompe disease is a progressive muscle disorder with a wide range of phenotypic presentations, caused by an inherited deficiency of acid alpha-glucosidase. Since 2004 only a limited number of patients have been treated with recombinant human alpha-glucosidase from rabbit milk whereas since 2006 enzyme replacement therapy (ERT) with alglucosidase alfa has been licensed for the treatment of Pompe disease. This systematic review evaluates the clinical efficacy and safety of alglucosidase alfa treatment of juvenile and adult patients with late-onset Pompe disease (LOPD). Studies of alglucosidase alfa treatment of LOPD patients-published up to January 2012-were identified by electronic searching of the EMBASE and MEDLINE databases, and manual searching of the reference lists. Data on ERT outcomes were extracted from selected papers and analyzed descriptively. No statistical analysis was performed owing to data heterogeneity. Twenty-one studies containing clinical data from 368 LOPD patients were analyzed. Overall, at least two-thirds of patients were stabilized or had improved creatine kinase levels and muscular and/or respiratory function following treatment with alglucosidase alfa. ERT was well tolerated; most adverse events were mild or moderate infusion-related reactions. In conclusion, alglucosidase alfa treatment is effective and well tolerated and attenuates progression of LOPD in most patients. Further research is required to investigate factors such as age at diagnosis, phenotypic presentation, and genotypic characteristics, identification of which may enable better clinical and therapeutic management of LOPD patients.

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  18. Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder.

    PubMed

    Chancellor, Michael B; Staskin, David R; Kay, Gary G; Sandage, Bobby W; Oefelein, Michael G; Tsao, Jack W

    2012-04-01

    Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain. Of note, permeability of the BBB increases with age and can also be affected by trauma, stress, and some diseases and medications. Passive crossing of a molecule across the BBB into the brain is dependent upon its physicochemical properties. Molecular characteristics that hinder passive BBB penetration include a large molecular size, positive or negative ionic charge at physiological pH, and a hydrophilic structure. Active transport across the BBB is dependent upon protein-mediated transporter systems, such as that of permeability-glycoprotein (P-gp), which occurs only for P-gp substrates, such as trospium chloride, darifenacin and fesoterodine. Reliance on active transport can be problematic since genetic polymorphisms of P-gp exist, and many commonly used drugs and even some foods are P-gp inhibitors or are substrates themselves and, due to competition, can reduce the amount of the drug that is actively transported out of the CNS. Therefore, for drugs that are preferred not to cross into the CNS, such as potent anticholinergics intended for the bladder, it is optimal to have minimal passive crossing of the BBB, although it may also be beneficial for the drug to be a substrate for an active efflux transport system. Anticholinergics demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine and trospium chloride are substrates for P-gp and, therefore, are actively transported away from the brain. In addition, trospium chloride has not been detected in cerebrospinal

  19. Adolescent abuse of dextromethorphan.

    PubMed

    Schwartz, Richard H

    2005-09-01

    Dextromethorphan hydrobromide (DXM), a constituent of more than 125 patent cough/cold remedies, is the most popular antitussive medication in the United States. Cough syrups or capsules also contain additional ingredients such as acetaminophen, chlorpheniramine maleate, guaifenesin, and/or pseudoephedrine, and toxicity with overdosage is additive to that of dextromethorphan alone. An unknown number of adolescents in the United States and Europe intoxicate themselves with acute megadoses of dextromethorphan. A megadose of DXM is defined as 5 to 10 times the dose recommended for control of annoying nonproductive coughs. Although a moderate overdose of pure DXM hydrobromide is free of serious adverse effects, approximately 5% of persons of European ethnicity lack the ability to metabolize the drug normally, leading to rapid acute toxic levels. Variable quantities of pure dextromethorphan powder in multiples of 1 gram are easily available from the worldwide web, including e-Bay. Recipe-like extraction procedures are quickly available on the Internet for seemingly simple and inexpensive home manufacture of concentrated dextromethorphan powder from Coricidin HBP Cough & Cold tablets (street name triple C). Adolescents intoxicate themselves at parties and even before or after school since the drug is legal, relatively inexpensive, and easily purchased or shoplifted at drug or convenient stores. Acute megadoses of the drug have profound psychological and physiological effects similar to those of phencyclidine (PCP). Megadoses of dextromethorphan used to self-intoxicate, can produce a false-positive screening test for phencyclidine in a urine specimen.

  20. The Styx field trial

    PubMed Central

    Gemmell, M. A.

    1968-01-01

    An assessment was made of the effectiveness of the generally accepted methods recommended for controlling hydatid disease during the course of a field-trial, initiated in 1943 in an isolated region of New Zealand. The results obtained during the first 21 years are described. Basically, the trial was an attempt to compare the effectiveness of a general public health educational programme and an anthelmintic programme using arecoline hydrobromide for treatment of dogs with that of a specific educational programme using this compound as a diagnostic agent. Arecoline hydrobromide was found to be too uncertain in its action to be of practical value as an anthelmintic. The development of diagnostic techniques, described in this paper, made it possible to use the compound for diagnostic purposes and thus for educational purposes, since each dog could be examined for tapeworms in the presence of the owner. Using changes in the annual prevalence rate in sheep of the cysts of E. granulosus and those of T. hydatigena as the principal indicators, the conclusion has been reached that the specific diagnostic approach achieved more success than the general educational and treatment programme. The principal reason for this appears to be that the former approach induced a greater awareness in owners of the need for strict management to prevent dogs gaining access to infective raw offal than that stimulated in the community when the dogs were dosed but not examined. ImagesFIG. 2FIG. 4FIG. 5 PMID:5303843

  1. High-performance liquid chromatographic assay for the simultaneous determination of ipratropium bromide, fenoterol, salbutamol and terbutaline in nebulizer solution.

    PubMed

    Jacobson, G A; Peterson, G M

    1994-06-01

    A reversed-phase ion-pair high-performance liquid chromatography assay was developed for the simultaneous determination of ipratropium bromide, fenoterol hydrobromide, salbutamol sulphate and terbutaline sulphate in nebulizer solution. Chromatographic separation was achieved with a Nova-Pak C18 4 microns 10 cm x 8 mm i.d. Radial-pak cartridge inside a Waters RCM 8 x 10 compression module using ternary gradient analysis. Detection was performed using UV detection at 220 nm. The standard curves were linear over the following ranges: ipratropium bromide 20.8-250.0 micrograms ml-1, fenoterol hydrobromide 27.8-500.0 micrograms ml-1, salbutamol sulphate 34.7-2500.0 micrograms ml-1 and terbutaline sulphate 69.5-2500 micrograms ml-1. Inter-day and intra-day relative standard deviations for each compound ranged from 4.5-5.2% and 3.5-3.9%, respectively. The assay procedure was developed to allow the accurate determination of constituents in various combinations of nebulizer solution, as well as for stability indicating purposes. This provides a convenient means of testing long-term compatibility and stability following the post-manufacture mixing of commonly used nebulized preparations. PMID:7918785

  2. Involvement of the serotonergic type 1A (5-HT1A) receptor in the agranular insular cortex in the consolidation of memory for inhibitory avoidance in rats.

    PubMed

    Mello e Souza, T; Rodrigues, C; Souza, M M; Vinadé, E; Coitinho, A; Choi, H; Izquierdo, I

    2001-09-01

    Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the agranular insular cortex of the prefrontal cortex. After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA footshock) and received, immediately after training, a 0.5-microl infusion of the serotonergic type 1A (5-HT1A) receptor agonist dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) or of the 5- HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190), or of vehicle alone (20% DMSO). Retention testing was carried out 24 h after training. 8-OH-DPAT (1.25 and 6.25 microg but not 0.0125 or 0.125 microg) was amnesic. NAN-190 was not effective at 0.125 or 1.25 microg any dose but reversed amnesia when given at 1.250 microg simultaneously with both effective doses of 8-OH-DPAT. These results show that an overactivation of 5-HT1A receptors in the agranular insular cortex impairs memory consolidation of inhibitory avoidance, in rats, immediately after training. This suggests that these receptors of the insular cortex may modulate memory consolidation.

  3. [Alpha-lipoic acid triggers elimination of cells with abnormal nuclei in human carcinoma epidermoid cell line].

    PubMed

    Kisurina-Evgen'eva, O P; Onishchenko, G E

    2010-01-01

    The skin is usually exposed to adverse environmental conditions that may cause pathological cell proliferation and cellular transformations leading to the formation of malignant cells. Antioxidants may affect these processes and induce the elimination of transformed cell. The purpose of this work was to investigate the effect of alfa-lipoic acid on human carcinoma epidermoid cell line A431. Our results showed that alfa-lipoic acid induced inhibition of cell proliferation or stimulated apoptotic cell death. Cells with abnormal nuclei were eliminated by apoptosis. Electron microscopy showed that survived cells had typical for control cells shape and organization of the nuclei, organization of the cytoplasm and organelles. Thus, alfa-lipoic acid not only triggered apoptosis of carcinoma cells, but it may also activate the mechanism of elimination of cells with abnormal chromosome number.

  4. [Busulfan versus busulfan-interferon as maintenance therapy in chronic myeloid leukemia].

    PubMed

    López Hernández, M A; Flores-Chapa, J D; Trueba Christy, E; Borbolla Escoboza, J R; Carrillo Rosales, T

    1996-01-01

    We studied 30 patients in order to evaluate the therapeutic efficacy and toxicity of alfa interferon associated with busulfan as maintenance treatment in de novo chronic granulocytic leukemia. Patients received 0.2 mg/kg of busulfan and reached complete hematological remission (CHR). Patients were then randomized in two groups: one to receive busulfan to be administered when the leukocyte count was above 15 x 10(9)/L, and another to receive subcutaneously 5 million IU of alpha-interferon three times per week (plus busulfan if the leukocyte count went above 15 x 10(9)/L). The duration of CHR was longer in the alfa-interferon group: 31 vs 16 months (p = 0.03) but no cytogenetic remissions were observed. Alfa interferon was well tolerated: no patient was excluded from the study due to toxicity. PMID:8966391

  5. Adhesion analysis of non-woven natural fibres in unsaturated polyester resin

    NASA Astrophysics Data System (ADS)

    Omri, Med Amin; Triki, A.; Guicha, M.; Ben Hassen, Med; Arous, M.; Ahmed El Hamzaoui, H.; Bulou, A.

    2015-03-01

    The presence of wool fibres in non-woven Alfa fibres sheet was investigated as a mean of improving adhesion of Alfa fibre-reinforced unsaturated polyester composite. FT-IR and Raman spectroscopy results revealed that such improvement could occur by a decrease in the hydrophilic character of the Alfa fibres owing to the presence of wool fibres. Hence, physical and chemical interactions could happen between the reinforcement and the matrix as demonstrated by FT-IR and Raman spectroscopy results. Tensile testing performed on this composite confirmed that such adhesion could occur according to its excellent specific parameters despite of its low tensile strength attributed to a higher fibre to fibre contact of wool fibres.

  6. Impairment of Type I but Not Type III IFN Signaling by Hepatitis C Virus Infection Influences Antiviral Responses in Primary Human Hepatocytes

    PubMed Central

    Friborg, Jacques; Ross-Macdonald, Petra; Cao, Jian; Willard, Ryan; Lin, Baiqing; Eggers, Betsy; McPhee, Fiona

    2015-01-01

    Peginterferon lambda-1a (Lambda), a type III interferon (IFN), acts through a unique receptor complex with limited cellular expression outside the liver which may result in a differentiated tolerability profile compared to peginterferon alfa (alfa). In Phase 2b clinical studies, Lambda administered in combination with ribavirin (RBV) was efficacious in patients with hepatitis C virus (HCV) infection representing genotypes 1 through 4, and was associated with more rapid declines in HCV RNA compared to alfa plus RBV. To gain insights into potential mechanisms for this finding, we investigated the effects of HCV replication on IFN signaling in primary human hepatocytes (PHH) and in induced hepatocyte-like cells (iHLCs). HCV infection resulted in rapid down-regulation of the type I IFN-α receptor subunit 1 (IFNAR1) transcript in hepatocytes while the transcriptional level of the unique IFN-λ receptor subunit IL28RA was transiently increased. In line with this observation, IFN signaling was selectively impaired in infected cells upon stimulation with alfa but not in response to Lambda. Importantly, in contrast to alfa, Lambda was able to induce IFN-stimulated gene (ISG) expression in HCV-infected hepatocytes, reflecting the onset of innate responses. Moreover, global transcriptome analysis in hepatocytes indicated that Lambda stimulation prolonged the expression of various ISGs that are potentially beneficial to antiviral defense mechanisms. Collectively, these observed effects of HCV infection on IFN receptor expression and signaling within infected hepatocytes provide a possible explanation for the more pronounced early virologic responses observed in patients treated with Lambda compared to alfa. PMID:25826356

  7. Assessing the endosulfan contamination in an unconfined aquifer.

    PubMed

    Atasoy, Ayse Dilek; Mermut, Ahmet Ruhi; Yesilnacar, Mehmet Irfan

    2012-02-01

    Groundwater samples were analyzed in order to elucidate the fate of endosulfan in the soil and its release mechanism into water of an unconfined aquifer. Residual alfa endosulfan was determined in all the wells; however, beta endosulfan was below 0.001 μg/L. Maximum adsorption rates of alfa and beta endosulfan were 91%-86% on the topsoil; 87%-91% on the subsoil, respectively. About 13%-23% desorption rate on the topsoil and subsoil exhibited the probability of endosulfan movement in the soil. The study showed that a hydrophobic-moderately persistent pesticide can reach to groundwater despite the high clay content of soil.

  8. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors

    PubMed Central

    Vegesna, Anil K.; Braverman, Alan S.; Miller, Larry S.; Tallarida, Ronald J.; Tiwana, Mansoor I.; Khayyam, Umar

    2010-01-01

    To compare the gastroesophageal junction of the human with the pig, M2 and M3 receptor densities and the potencies of M2 and M3 muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M2 receptors are higher in pig than human clasp and sling fibers. M3 receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M3 receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M2 receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M3 receptors mediate contraction in pig sling fibers and that M2 and M3 receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M2 and M3 muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers. PMID:20133950

  9. Managing Urinary Incontinence in Patients with Dementia: Pharmacological Treatment Options and Considerations.

    PubMed

    Orme, Susie; Morris, Vikky; Gibson, William; Wagg, Adrian

    2015-07-01

    Urinary incontinence and lower urinary tract symptoms are highly prevalent in late life and are strongly associated with dementia and frailty. Incontinence is extremely common among those living in long-term care and is most commonly due to urgency incontinence. Although national and international guidelines for continence care exist, they often fail to consider the complex comorbidity found in patients with dementia and are often not followed; continence practices in long-term care may promote rather than prevent incontinence. The majority of those with dementia living in the community can be managed successfully with standard treatments, both pharmacological and non-pharmacological; the expectations and aims of treatment of both the patient and their caregivers should be considered. A dementia diagnosis does not preclude management of incontinence, but treatment options may be more limited in those with advanced dementia who are unable to retain information and modify behaviors. High-quality data to guide the choice of pharmacological agent in those with dementia are lacking. Oxybutynin has been shown to have significant adverse cognitive effects, but data to support the use of trospium, solifenacin, darifenacin, and fesoterodine are limited. No data are available for mirabegron. Neither age, frailty, nor dementia should be considered a barrier to pharmacological management, but consideration should be given to the total anticholinergic load. Evidence to guide the treatment of incontinence in this vulnerable patient group is scarce, and available guidelines adapted for each individual's situation should be applied. PMID:26169438

  10. Pharmacological approaches to targeting muscarinic acetylcholine receptors.

    PubMed

    Matera, Carlo; Tata, Ada M

    2014-01-01

    The presence of cholinergic system markers and muscarinic receptor subtypes in several tissues also of nonneuronal type has been largely demonstrated. Acetylcholine, synthesized in the nervous system, can locally contribute to modulate cell proliferation, survival and apoptosis. Considering that the cholinergic system functions are impaired in a number of disorders, the identification of new drugs regulating these functions appears of great clinical relevance. The possible involvement of muscarinic acetylcholine receptors in different pathologies has been proposed in recent years and is becoming an important area of study. However, the lack of selective muscarinic receptor ligands has for long time limited the therapeutic treatment based on muscarinic receptors as targets. To date, some muscarinic ligands such as xanomeline (patent, US5980933) or cevimeline (patents US4855290, US5571918) have been developed for the treatment of several pathologies (Alzheimer's and Sjogren's diseases). The present review will be focused on the potential effects produced by muscarinic receptor activation in different pathologies, including tumors. In fact, the potential use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that several muscarinic antagonists, already used in the treatment of genitourinary diseases (e.g. darifenacin, patent, US5096890, US6106864), have also been demonstrated to arrest the tumor growth in vivo. Moreover, the contribution of muscarinic receptors to analgesia is also reviewed. Finally, some of the most significant achievements in the field of bitopic/dualsteric ligands will be discussed and the molecules patented so far will be presented.

  11. Managing Urinary Incontinence in Patients with Dementia: Pharmacological Treatment Options and Considerations.

    PubMed

    Orme, Susie; Morris, Vikky; Gibson, William; Wagg, Adrian

    2015-07-01

    Urinary incontinence and lower urinary tract symptoms are highly prevalent in late life and are strongly associated with dementia and frailty. Incontinence is extremely common among those living in long-term care and is most commonly due to urgency incontinence. Although national and international guidelines for continence care exist, they often fail to consider the complex comorbidity found in patients with dementia and are often not followed; continence practices in long-term care may promote rather than prevent incontinence. The majority of those with dementia living in the community can be managed successfully with standard treatments, both pharmacological and non-pharmacological; the expectations and aims of treatment of both the patient and their caregivers should be considered. A dementia diagnosis does not preclude management of incontinence, but treatment options may be more limited in those with advanced dementia who are unable to retain information and modify behaviors. High-quality data to guide the choice of pharmacological agent in those with dementia are lacking. Oxybutynin has been shown to have significant adverse cognitive effects, but data to support the use of trospium, solifenacin, darifenacin, and fesoterodine are limited. No data are available for mirabegron. Neither age, frailty, nor dementia should be considered a barrier to pharmacological management, but consideration should be given to the total anticholinergic load. Evidence to guide the treatment of incontinence in this vulnerable patient group is scarce, and available guidelines adapted for each individual's situation should be applied.

  12. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.

  13. Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes.

    PubMed

    van Dussen, Laura; Cox, Timothy M; Hendriks, Erik J; Morris, Elizabeth; Akkerman, Erik M; Maas, Mario; Groener, Johanna E M; Aerts, Johannes M F G; Deegan, Patrick B; Hollak, Carla E M

    2012-12-01

    This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched to treatment with velaglucerase alfa after 1-8.5 months of dose reduction. The course of important Gaucher disease parameters was studied at four time points: one year before the shortage, just before the shortage, before a switch to velaglucerase and after up to one year of treatment with velaglucerase. These parameters included hemoglobin concentration, platelet count, plasma chitotriosidase activity in all patients, and spleen and liver volumes (as well as bone marrow fat fraction images) in 10 patients. Decreases in platelet counts as a result of reduced treatment with imiglucerase were quickly restored on treatment with velaglucerase alfa. Chitotriosidase activity declined overall after switching. Five out of 10 patients had an increase in liver volume of at least 10% after six months of velaglucerase treatment, which was reversible in 3. Most patients received infusions at home and no important side effects were observed. Velaglucerase alfa appears to be a safe and effective alternative for imiglucerase. PMID:22773601

  14. 77 FR 14593 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to Executive Order 12978

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... (Colombia) (individual) 3. CASQUETE VARGAS, Orlando, c/o ALFA PHARMA S.A., Bogota, Colombia; c/o...) (``IEEPA''), issued Executive Order 12978 (60 FR 54579, October 24, 1995) (the ``Order''). In the Order... 1962; Cedula No. 79261845 (Colombia) (individual) 18. VARGAS VASQUEZ, Jorge Alberto, c/o AMERICANA...

  15. 77 FR 43429 - Unblocking of 1 Individual and 2 Entities Designated Pursuant to Executive Order 13315

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... TRADING AND MARKETING, P.O. Box 212953, Amman 11121, Jordan; c/o ALFA COMPANY LIMITED FOR INTERNATIONAL TRADING AND MARKETING, P.O. Box 910606, Amman 11191, Jordan; c/o TRADING AND TRANSPORT SERVICES, Al- Razi Medical Complex, Jabal Al-Hussein, Amman, Jordan; c/o TRADING AND TRANSPORT SERVICES, P.O. Box...

  16. The Training of Music Teachers in Colombia: A Descriptive Analysis

    ERIC Educational Resources Information Center

    Nayibe Cárdenas Soler, Ruth; Lorenzo Quiles, Oswaldo; Hargreaves, David J.

    2015-01-01

    This study is an evaluative analysis of 13 Music Education programs in Colombia that provide training for secondary school music teachers for 6th to 11th grade in the Colombian education system. The study utilized an analysis matrix from the International Research Project ALFA II-0448-A, which developed a similar study with Latin American and…

  17. 49 CFR Appendix A to Part 220 - Recommended Phonetic Alphabet

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... appendix A of part 220 does not exist in 49 CFR parts 200 to 399, revised as of Oct. 1, 1997. ...—Recommended Phonetic Alphabet A—ALFA B—BRAVO C—CHARLIE D—DELTA E—ECHO F—FOXTROT G—GOLF H—HOTEL I—INDIA...

  18. Design and rationale of the Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin After Large Myocardial Infarction (REVEAL) trial

    PubMed Central

    Melloni, Chiara; Rao, Sunil V.; Povsic, Thomas J.; Melton, Laura; Kim, Raymond J.; Kilaru, Rakhi; Patel, Manesh; Talan, Mark; Ferrucci, Luigi; Longo, Dan L.; Lakatta, Edward G.; Najjar, Samer S.; Harrington, Robert A.

    2010-01-01

    Background Acute myocardial infarction (MI) remains a leading cause of death despite advances in pharmacologic and percutaneous therapies. Animal models of ischemia/reperfusion have demonstrated that single-dose erythropoietin (EPO) may reduce infarct size, decrease apoptosis, and increase neovascularization, possibly through mobilization of endothelial progenitor cells (EPCs). Study Design REVEAL is a randomized, double-blind, placebo-controlled, multicenter trial evaluating the effects of epoetin alfa on infarct size and left ventricular (LV) remodeling in patients with large MIs. The trial comprises a dose-escalation safety phase and a single-dose efficacy phase using the highest acceptable epoetin alfa dose up to 60,000 units. Up to 250 STEMI patients undergoing primary or rescue percutaneous coronary intervention (PCI) will be randomized to intravenous epoetin alfa or placebo within 4 hours of successful reperfusion. The primary study endpoint is infarct size expressed as a percentage of LV mass, as measured by cardiac magnetic resonance imaging 2–6 days post study medication administration. Secondary endpoints will assess changes in EPC numbers and changes in indices of ventricular remodeling. Conclusion The REVEAL trial will evaluate the safety and efficacy of the highest tolerated single dose of epoetin alfa in patients who have undergone successful rescue or primary PCI for acute STEMI. PMID:21095264

  19. 49 CFR Appendix A to Part 220 - Recommended Phonetic Alphabet

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... appendix A of part 220 does not exist in 49 CFR parts 200 to 399, revised as of Oct. 1, 1997. ...—Recommended Phonetic Alphabet A—ALFA B—BRAVO C—CHARLIE D—DELTA E—ECHO F—FOXTROT G—GOLF H—HOTEL I—INDIA...

  20. Testing Adjuvant Ipilimumab in Advanced Melanoma

    Cancer.gov

    In this clinical trial, patients with stage III or stage IV melanoma that has been completely resected will be randomly assigned to receive post-surgical treatment with either ipilimumab or high-dose interferon alfa-2b, the current standard of care.

  1. Electronic Publishing in Librarianship and Information Science in Latin America--A Step towards Development?

    ERIC Educational Resources Information Center

    Johnson, Ian M.; Cano, Virginia

    2008-01-01

    Introduction: This paper draws on the results of studies undertaken between 2004 and 2007 as part of Project REVISTAS, supported by the European Commission's ALFA Programme. Method: A variety of methods was employed over the life of the project, including analysis of directories, a survey of universities in the region believed to be offering…

  2. African Americans Respond Poorly to Hepatitis C Treatment

    ERIC Educational Resources Information Center

    Black Issues in Higher Education, 2004

    2004-01-01

    African Americans have a significantly lower response rate to treatment for chronic hepatitis C than non-Hispanic Whites, according to a new study led by Duke University Medical Center researchers. Some African Americans--19 percent--did respond to the drug combination of peginterferon alfa-2b and ribavirin. But in non-Hispanic Whites with the…

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  4. 49 CFR Appendix A to Part 220 - Recommended Phonetic Alphabet

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... appendix A of part 220 does not exist in 49 CFR parts 200 to 399, revised as of Oct. 1, 1997. ...—Recommended Phonetic Alphabet A—ALFA B—BRAVO C—CHARLIE D—DELTA E—ECHO F—FOXTROT G—GOLF H—HOTEL I—INDIA...

  5. 49 CFR Appendix A to Part 220 - Recommended Phonetic Alphabet

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... appendix A of part 220 does not exist in 49 CFR parts 200 to 399, revised as of Oct. 1, 1997. ...—Recommended Phonetic Alphabet A—ALFA B—BRAVO C—CHARLIE D—DELTA E—ECHO F—FOXTROT G—GOLF H—HOTEL I—INDIA...

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. PMID:16082427

  10. Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

    PubMed Central

    McVicar, Carmel M.; Colhoun, Liza M.; Abrahams, Jodie L.; Kitson, Claire L.; Hamilton, Ross; Medina, Reinhold J.; Durga, Dash; Gardiner, Tom A.; Rudd, Pauline M.; Stitt, Alan W.

    2010-01-01

    Background Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. Methodology/Principal Findings The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1–20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFα and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). Conclusions This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs. PMID:20686695

  11. Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior

    PubMed Central

    King, Bryan H.; Hollander, Eric; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Bregman, Joel D.; Donnelly, Craig L.; Anagnostou, Evdokia; Dukes, Kimberly; Sullivan, Lisa; Hirtz, Deborah; Wagner, Ann; Ritz, Louise

    2014-01-01

    Context Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. Objectives To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. Design National Institutes of Health–sponsored randomized controlled trial. Setting Six academic centers, including Mount Sinai School of Medicine, North Shore–Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. Participants One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Interventions Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). Main Outcome Measures Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. Results There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95

  12. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

    PubMed Central

    Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek

    2016-01-01

    Background Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0–9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with

  13. Cost-effectiveness of Treatment for Hepatitis C in an Urban Cohort Co-infected with HIV

    PubMed Central

    Campos, Nicole G.; Salomon, Joshua A.; Servoss, Julie C.; Nunes, David P.; Samet, Jeffrey H.; Freedberg, Kenneth A.; Goldie, Sue J.

    2007-01-01

    PURPOSE Recent clinical trials have evaluated treatment strategies for chronic infection with hepatitis C virus (HCV) in patients co-infected with human immunodeficiency virus (HIV). Our objective was to use these data to examine the cost-effectiveness of treating HCV in an urban cohort of co-infected patients. METHODS A computer-based model, together with available published data, was used to estimate lifetime costs (2004 US dollars), life expectancy, and incremental cost per year of life saved (YLS) associated with 3 treatment strategies: (1) interferon-alfa and ribavirin; (2) pegylated interferon-alfa; and (3) pegylated interferon-alfa and ribavirin. The target population included treatment-eligible patients, based on an actual urban cohort of HIV-HCV co-infected subjects, with a mean age of 44 years, of whom 66% had genotype 1 HCV, 16% had cirrhosis, and 98% had CD4 cell counts >200 cells/mm3. RESULTS Pegylated interferon-alfa and ribavirin was consistently more effective and cost-effective than other treatment strategies, particularly in patients with non-genotype 1 HCV. For patients with CD4 counts between 200 and 500 cells/mm3, survival benefits ranged from 5 to 11 months, and incremental cost-effectiveness ratios were consistently less than $75,000 per YLS for men and women of both genotypes. Due to better treatment efficacy in non-genotype 1 HCV patients, this group experienced greater life expectancy gains and lower incremental cost-effectiveness ratios. CONCLUSIONS Combination therapy with pegylated interferon-alfa and ribavirin for HCV in eligible co-infected patients with stable HIV disease provides substantial life-expectancy benefits and appears to be cost-effective. Overcoming barriers to HCV treatment eligibility among urban co-infected patients remains a critical priority. PMID:17349451

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

    (+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride, Ambrisentan, Amsilarotene, Anacetrapib, Anakinra, Apricitabine, Aripiprazole, Arsenic trioxide, Atazanavir sulfate, Atazanavir/ritonavir, Atrasentan, Azacitidine; Banoxantrone, Bazedoxifene acetate, Bevacizumab, Bexarotene, Biphasic insulin aspart, Bortezomib, Bosentan, Bromfenac; Cachectin, Calcipotriol/betamethasone dipropionate, Canakinumab, Carfilzomib, CAT-354, CCX-282, Certolizumab pegol, Cetuximab, Choline fenofibrate, Clevudine, Clofarabine, CNTO-328, Corifollitropin alfa, Crofelemer; Daptomycin, Darbepoetin alfa, Darunavir, Dasatinib, Decitabine, Deferasirox, Denosumab, Duloxetine hydrochloride, Dutasteride; Emtricitabine, Enfuvirtide, Entecavir, Epoetin zeta, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Farglitazar, Febuxostat, Fosamprenavir calcium, FX-06; Gabapentin enacarbil, Gefitinib; HIVIS DNA; Imatinib mesylate, INCB- 18424, Indacaterol, Inotuzumab ozogamicin, Insulin detemir; JNJ-26854165; Lacosamide, Landiolol, Laromustine, Lenalidomide, Liposomal doxorubicin, L-NAME, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Maraviroc, Mepolizumab, Methoxy polyethylene glycol- epoetin-beta, Miglustat, MK-0493, MVA-CMDR, Mycophenolic acid sodium salt; Natalizumab, Nepafenac, Neratinib, Neridronic acid, Nesiritide, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate, Omalizumab; Paclitaxel poliglumex, Palifermin, Patupilone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, PHA-848125, Pitavastatin calcium, Posaconazole, Povidone-iodine liposome complex, Prasugrel, Pregabalin, Prucalopride; Raltegravir potassium, Retigabine, Revaprazan hydrochloride, rhFSH, Rilpivirine, Rivaroxaban, Romidepsin

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  16. Effect of age on upregulation of the cardiac adrenergic beta receptors

    SciTech Connect

    Tumer, N.; Houck, W.T.; Roberts, J.

    1990-03-01

    Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors.

  17. Neuroleptic Malignant syndrome (NMS): a rare presentation induced by an antiemetic - case report.

    PubMed

    Kashyap, Gursharan Lal; Patel, Ashok G

    2011-09-01

    Neuroleptic Malignant Syndrome is one of the life threatening complications of antipsychotic psychotropic medication. We here report a case of a 39 years old male who has had a diagnosis of paranoid schizophrenia since the age of 18. He had been on antipsychotic therapy since then. He was stable on a combination of antipsychotics. He had mild hyper-salivation for a long time but was not very concerned about it. He requested and was prescribed Hyoscine Hydrobromide 300 mcg BD for hyper-salivation. There was no other medication change. After 5 days of starting Kwells, the patient presented with Neuroleptic Malignant syndrome. One has to watch for NMS while starting Hyoscine Hydrbromide for someone on antispychotics.

  18. [Isolation and structure identification of chemical constituents from the skin of Bufo bufo gargarizans].

    PubMed

    Dai, Li-Ping; Gao, Hui-Min; Wang, Zhi-Min; Wang, Wei-Hao

    2007-08-01

    The skin of Bufo bufo gargarizans, originated from Bufo bufo gargarizans Cantor (Bufonidae), is widely used in traditional Chinese medicine for the treatment of hepatoma, lung cancer and etc. The preparation of the aqueous components has significant therapeutic effect against the digestive tract cancer. The water-soluble chemical constituents in the skin of Bufo bufo gargarizans were then investigated to make clear the active compounds. Six compounds were isolated and purified by recrystallization and column chromatography on silica gel and ODS, their structures were elucidated as 4-amido-3-hydroxymethyl-cyclooctylamidezotetra-alpha-furanone (I), bufogargarizanine C (II), bufothionine (III), dehydrobufotenine hydrobromide (IV), suberic acid (V) and succinic acid (VI) on the basis of physicochemical properties and spectral data (UV, IR, 1H NMR, 13C NMR and MS). Of the above compounds, compounds I and II are new compounds and named bufogargarizanine B and C, respectively. PMID:17944235

  19. Multivariate optimization and validation of a capillary electrophoresis method for the simultaneous determination of dextromethorphan hydrobromur, phenylephrine hydrochloride, paracetamol and chlorpheniramine maleate in a pharmaceutical preparation using response surface methodology.

    PubMed

    Palabiyik, I Murat; Onur, Feyyaz

    2010-01-01

    A fast, accurate, precise and sensitive capillary electrophoresis method for the simultaneous determination of dextromethorphan hydrobromide, phenylephrine hydrochloride, paracetamol and chlorpheniramine maleate has been developed. Response surface methodology with a central composite design was used for optimization of the concentration of the buffer, pH of the buffer and applied voltage. Therefore, working with Na(2)HPO(4) buffer (pH 8.00, 0.01 M) at 20 kV as an applied voltage in the capillary electrophoresis method were found to be suitable; under these optimal conditions, these four active ingredients were separated in about 7 min. This developed method was validated and successfully applied to a pharmaceutical preparation, sugar-coated tablet, and the results were compared with a high-performance liquid chromatographic method developed by us.

  20. [Long-term treatment with psychoverlan in children and adolescents with behavior disorders].

    PubMed

    Heinze, H

    1978-08-24

    Numerous pharmacological and clinical long-term studies on mono-magnesium-L-glutamate-hydrobromide. H2O were reason to undertake another trial in adolescents with reactive behavioral abnormalities. The aim of the study was to assess the effecacy of Psychoverlan in abolishing or improving these symptoms and to reveal any possible drug-induced side effects. In a long-term study 19 young females were treated with Psychoverlan capsules or syrup for an average of 11.4 months. Intolerance phenomena and side-effects were not seen. It was even decided to increase the standard dose. None of the patients developed brominism or bromine intoxication. The general state of health of 13 of the 19 subjects was improved by the harmonizing effect of the drug on psychic and vegetative functions. Tiredness and somnolence were not observed. PMID:680616

  1. Inhibition of artificially induced cough in man by bronchodilators.

    PubMed Central

    Lowry, R; Higenbottam, T; Johnson, T; Godden, D

    1987-01-01

    1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 micrograms; 14 volunteers) both significantly reduced couch compared with placebo (P less than 0.01). Oral salbutamol sulphate (4 mg; 11 volunteers) and oral pirenzepine hydrochloride (50 mg; 14 volunteers) had lesser effects. 4. Cough inhibition correlated with a small but statistically significant degree of bronchodilatation as measured by specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) in six normal subjects studied with each treatment in a placebo controlled, double blind study (r = 0.67, P less than 0.001). 5. Small reductions in airway tone are associated with a reduced cough response elicited by inhaled ultrasonically nebulized distilled water. PMID:3689630

  2. Pathways of the eye's response to topical nitrogen mustard.

    PubMed

    Jampol, L M; Axelrod, A; Tessler, H

    1976-06-01

    We studied the effect of prior corneal herpes simplex infection with its resultant corneal hypesthesia on the irritative response of the rabbit eye to topical nitrogen mustard. Both the miosis and the breakdown of the blood-aqueous barrier that follow the application of topical nitrogen mustard were diminished in eyes infected three weeks previously with herpes simplex virus. Nonspecific corneal scarring did not affect the response. This suggests again that an axon reflex requiring intact sensory innervation mediates the response to nitrogen mustard. Pretreatment of normal (noninfected) rabbits with systemic H1 and H2 antihistamines, topical scopolamine hydrobromide, or topical and systemic corticosteroids was ineffective in blocking the miosis or increased protein in the aqueous humor following topical nitrogen mustard. PMID:6401

  3. Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and butyrylcholinesterase inhibitors.

    PubMed

    Granica, Sebastian; Kiss, Anna K; Jarończyk, Małgorzata; Maurin, Jan K; Mazurek, Aleksander P; Czarnocki, Zbigniew

    2013-11-01

    In this study, we synthesized several imperatorin analogs using imperatorin and xanthotoxin as substrates. The anti-cholinesterase activities of all compounds were evaluated in in vitro experiments according to the modified Ellman's method. For each synthesized compound, IC50 values for both enzymes were established. Galantamine hydrobromide was used as a positive control in the enzymatic experiments. All active compounds showed selectivity toward butyrylcholinesterase (BuChE) rather than acetylcholinesterase. The most active ones were 8-(3-methylbutoxy)-psoralen and 8-hexoxypsoralen with IC50 values for BuChE of around 16.5 and 16.4 µM, respectively. The results of our study may be considered as the beginning of a search for potential anti-Alzheimer's disease drugs based on the structure of natural furocoumarins. PMID:24123207

  4. Metronidazole-Induced Bullous Pemphigoid: A Case Report.

    PubMed

    Moitra, Saibal; Sen, Sukanta; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-12-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  5. Gypsogenin derivatives: an unexpected class of inhibitors of cholinesterases.

    PubMed

    Heller, Lucie; Schwarz, Stefan; Weber, Björn A; Csuk, René

    2014-10-01

    Gypsogenin (1) was obtained by acidic hydrolysis from its saponin. While the parent compound 1 acted as a selective inhibitor for butyrylcholinesterase (from equus) possessing a moderate mixed-type inhibition of the enzyme, Ki values as low as 2.67 ± 0.59 μM were determined for (3β,4α) 3-O-acetyl-olean-12-ene-23,28-dinitrile (11) and acetylcholinesterase (AChE, from electric eel). Thus, 11 possesses one-fifth of the inhibitory activity of the "gold standard" galantamine hydrobromide; this compound is one of the first pentacyclic triterpenoids described as a potent AChE-selective inhibitor. PMID:25042600

  6. Utility of polymer-supported reagents in the total synthesis of lamellarins.

    PubMed

    Ploypradith, Poonsakdi; Kagan, Rachel Kirk; Ruchirawat, Somsak

    2005-06-24

    Four solid-supported reagents have been utilized in the multistep synthesis of lamellarins. The use of Amberlyst A-26 Br(3)(-) and polymer bound pyridine hydrobromide perbromide (PVPHP) for keto alpha-bromination of the less studied ortho-substituted acetophenone derivatives selectively furnished the corresponding monobromination products (phenacyl bromide derivatives), which were used directly in condensation reactions with benzyldihydroisoquinoline mediated by Amberlyst A-26 NaCO(3)(-). The 2H-pyrrole carbonates subsequently underwent intramolecular Friedel-Crafts transacylation followed by lactonization to provide the lamellarin skeleton. Alternatively, Amberlyst A-26 NaCO(3)(-) effectively served as base in condensation reaction of benzyldihydroisoquinoline with alpha-nitrocinnamate derivatives to provide the corresponding 2-ethoxycarbonyl pyrroles, which smoothly underwent O-debenzylation reaction followed by lactonization to furnish the lamellarin skeleton. The novel Amberlyst-15 mediated lactonization reactions effectively combined the otherwise two separate steps into a single transformation.

  7. Therapeutic effectiveness of medications taken during spaceflight

    NASA Technical Reports Server (NTRS)

    Pool, Sam L.; Putcha, Lakshmi

    1992-01-01

    The therapeutic effectiveness of medications during spaceflight is considered in light of extensive anecdotal and experimental evidence. Attention is given to a range of medications for space motion sickness, sleeplessness, and physical discomfort. About 70 individual cases are reviewed in which crewmembers used such medications as: (1) scopolamine hydrobromide, dextroamphetamine sulfate, and promethazine hydrochloride for motion sickness; (2) metoclopramide hydrochloride and naloxone hydrochloride for bowel motility; and (3) aspirin and acetaminophen for headache and back pain. The effectiveness of orally ingested medications for space motion sickness is shown to be very low, while promethazine hydrochloride is effective when administered intramuscularly. The medications for pain are shown to be generally effective, and the use of sleep-inducing medications is limited by potentially detrimental performance effects.

  8. Identification and estimation of the levo isomer in raw materials and finished products containing atropine and/or hyoscyamine.

    PubMed

    Cieri, Ugo R

    2005-01-01

    The belladonna alkaloids atropine sulfate and hyoscyamine sulfate, occasionally used as anticholinergic and antimuscarinic agents, have identical molecular formulas but different stereo configurations. Hyoscyamine sulfate contains almost 100% of the levo isomer, whereas atropine sulfate is composed of equal parts of dextro and levo isomers. It is believed that the therapeutic properties of these alkaloids are due exclusively or primarily to the levo isomer. Currently available methods determine only the total amount of atropine (hyoscyamine) sulfate. A method has been developed and is reported for the identification and estimation of the levo and dextro isomers of atropine and hyoscyamine. Reference solutions are prepared in methanol at the following weights per 100 mL: 8.0 mg atropine sulfate; 4.0 mg hyoscyamine sulfate; 7.0 mg scopolamine hydrobromide; and 10.0 mg homatropine methylbromide. Samples of raw materials are similarly prepared in methanol, commercial products are also extracted or diluted with methanol, and solutions are filtered. Liquid chromatography is used for separations on a 25 cm Chirobiotic T2 column. The mobile phase is prepared by mixing 3.0 mL acetic acid and 2.0 mL triethylamine with 1000 mL methanol. The injection volume is 100 or 200 microL; the flow rate is about 0.35 mL/min. Fluorescence detection is at 255 nm excitation and 285 nm emission. Scopolamine hydrobromide and hyoscyamine eluted after 20 and 60 min, respectively. Atropine sulfate generated 2 peaks after 60 and 65 min. Homatropine methylbromide also produced 2 peaks after 70 and 85 min. Samples tested in this study included raw materials and commercial tablets or injections containing belladonna alkaloids. In all cases, the percentage calculated was that of the levo isomer relative to the total amount of atropine (hyoscyamine) present.

  9. Potential inhibitors of L-asparagine biosynthesis. 5. Electrophilic amide analogues of (S)-2,3-diaminopropionic acid.

    PubMed

    Mokotoff, M; Logue, L W

    1981-05-01

    Three electrophilic amide analogues of (S)-2,3-diaminopropionic acid (1, DAP) have been prepared as potential inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma, EC 6.3.5.4). DAP was selectively blocked by the carbobenzoxy (Cbz) group to give 3-N-Cbz-DAP (2a). Esterification of 2a with isobutylene afforded tert-butyl 3-N-carbobenzoxy-(S)-2,3-diaminopropionate (3a), which was then blocked at the 2 position with the tert-butoxycarbonyl (Boc) group to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-[(carbobenzoxy)amino]propionate (4). Selective cleavage of the Cbz group by H2/Pd gave the key intermediate tert-butyl 2-N-(tert-butoxycarbonyl)-(S)-2,3-diaminopropionate (5), which was acylated, via the N-hydroxysuccinimide esters, with bromoacetic acid, dichloroacetic acid, and fumaric acid monoethyl ester to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)-amino]-3-(2-bromoacetamido)propionate (6a), tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(2,2-dichloroacetamido)propionate (6b), and tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(ethoxycarbonyl)acrylamido]-propionate (6c), respectively. Deblocking of 6a-c gave the corresponding amino acids (S)-2-amino-3-(2-bromoacetamido)propionic acid hydrobromide (7a), (S)-2-amino-3-(2,2-dichloroacetamido)propionic acid (7b), and ethyl N-[(S)-2-amino-2-carboxyethyl]fumarate (7c). By a slightly different procedure, 5 was converted in two steps to (S)-2-amino-3-acetamidopropionic acid hydrobromide (7d). The inhibition of ASase by 7a-c at 1 mM was 93, 19, and 37%, respectively, while 7d was without inhibition at 2 mM. Compounds 7a-c failed to increase the life span of mice infected with B16 melanoma.

  10. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014)

    PubMed Central

    Oelke, Matthias; Becher, Klaus; Castro-Diaz, David; Chartier-Kastler, Emmanuel; Kirby, Mike; Wagg, Adrian; Wehling, Martin

    2015-01-01

    Aim: we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. Methods: to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. Results: for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. Conclusions: dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). PMID:26104505

  11. A Novel Muscarinic Antagonist R2HBJJ Inhibits Non-Small Cell Lung Cancer Cell Growth and Arrests the Cell Cycle in G0/G1

    PubMed Central

    Liu, Xiaoyan; Ma, Xiaoyun; He, Xinhua; Zhuo, Rengong; Zhao, Zhe; Wang, Liyun; Yan, Haitao; Zhong, Bohua; Zheng, Jianquan

    2012-01-01

    Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs). In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC) cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC. PMID:23285263

  12. Contractions of the mouse prostate elicited by acetylcholine are mediated by M(3) muscarinic receptors.

    PubMed

    White, Carl W; Short, Jennifer L; Haynes, John M; Matsui, Minoru; Ventura, Sabatino

    2011-12-01

    Increased smooth muscle tone in the human prostate contributes to the symptoms associated with benign prostatic hyperplasia. In the mouse prostate gland, cholinergic innervation is responsible for a component of the nerve-mediated contractile response. This study investigates the muscarinic receptor subtype responsible for the cholinergic contractile response in the mouse prostate gland. To characterize the muscarinic receptor subtype, mouse prostates taken from wild-type or M(3) muscarinic receptor knockout mice were mounted in organ baths. The isometric force that tissues developed in response to electrical-field stimulation or exogenously applied cholinergic agonists in the presence or absence of a range of muscarinic receptor antagonists was evaluated. Carbachol elicited reproducible and concentration-dependent contractions of the isolated mouse prostate, which were antagonized by the presence of muscarinic receptor antagonists. Calculation of antagonist affinities (pA(2) values) indicated a rank order of antagonist potencies in the mouse prostate of: darifenacin (9.08) = atropine (9.07) = 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (9.02) > cyclohexyl-hydroxy-phenyl-(3-piperidin-1-ylpropyl)silane (7.85) > cyclohexyl-(4-fluorophenyl)-hydroxy-(3-piperidin-1-ylpropyl)silane (7.39) > himbacine (7.19) > pirenzipine (6.88) > methoctramine (6.20). Furthermore, genetic deletion of the M(3) muscarinic receptor inhibited prostatic contractions to electrical-field stimulation or exogenous administration of acetylcholine. In this study we identified that the cholinergic component of contraction in the mouse prostate is mediated by the M(3) muscarinic receptor subtype. Pharmacological antagonism of the M(3) muscarinic receptor may be a beneficial additional target for the treatment of benign prostatic hyperplasia in the human prostate gland.

  13. Role of Cholinergic Innervation and RGS2 in Atrial Arrhythmia

    PubMed Central

    Jones, Douglas L.; Tuomi, Jari M.; Chidiac, Peter

    2012-01-01

    The heart receives sympathetic and parasympathetic efferent innervation as well as the ability to process information internally via an intrinsic cardiac autonomic nervous system (ICANS). For over a century, the role of the parasympathetics via vagal acetylcholine release was related to controlling primarily heart rate. Although in the late 1800s shown to play a role in atrial arrhythmia, the myocardium took precedence from the mid-1950s until in the last decade a resurgence of interest in the autonomics along with signaling cascades, regulators, and ion channels. Originally ignored as being benign and thus untreated, recent emphasis has focused on atrial arrhythmia as atrial fibrillation (AF) is the most common arrhythmia seen by the general practitioner. It is now recognized to have significant mortality and morbidity due to resultant stroke and heart failure. With the aging population, there will be an unprecedented increased burden on health care resources. Although it has been known for more than half a century that cholinergic stimulation can initiate AF, the classical concept focused on the M2 receptor and its signaling cascade including RGS4, as these had been shown to have predominant effects on nodal function (heart rate and conduction block) as well as contractility. However, recent evidence suggests that the M3 receptor may also playa role in initiation and perpetuation of AF and thus RGS2, a putative regulator of the M3 receptor, may be a target for therapeutic intervention. Mice lacking RGS2 (RGS2−/−), were found to have significantly altered electrophysiological atrial responses and were more susceptible to electrically induced AF. Vagally induced or programmed stimulation-induced AF could be blocked by the selective M3R antagonist, darifenacin. These results suggest a potential surgical target (ICANS) and pharmacological targets (M3R, RGS2) for the management of AF. PMID:22754542

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-06-01

    [¹¹C]RAC; (18)F-Fluoromisonidazole; 89-12; 9-[¹⁸F]Fluoropropyl-(+)-dihydrotetrabenazine; Adalimumab, Adecatumumab, ADMVA, ADXS-11-001, Aflibercept, Agatolimod sodium, AGS-004, Alglucosidase alfa, Aliskiren fumarate, Alvocidib hydrochloride, AMG-108, AMG-853, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride; Bevacizumab, BioMatrix Flex drug eluting stent, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, Cediranib, Cetuximab, ChimeriVax-Dengue, Choriogonadotropin alfa, Cinacalcet hydrochloride, Cizolirtine citrate, Clofarabine, Cocaine conjugate vaccine, CX-717; Darbepoetin alfa, Dasatinib, Decitabine, Denosumab, Desvenlafaxine succinate, Dexamethasone sodium phosphate, Dienogest, Diphencyprone, Doripenem, DTaP-HepB-IPV, Dutasteride; E-7010, Ecallantide, Ecstasy, Eicosapentaenoic acid/docosahexaenoic acid, Emtricitabine, Enfuvirtide, Erlotinib hydrochloride, Eszopiclone, Etonogestrel/ethinyl estradiol, Etoricoxib, Everolimus, Everolimus-eluting coronary stent EVT-201, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumavate, Figitumumab, Filgrastim, Fingolimod hydrochloride, Fluticasone furoate, Fluval P, Fluzone, Fondaparinux sodium, Fulvestrant, Fungichromin; Gamma-hydroxybutyrate sodium, Gefitinib, GHB-01L1, GLY-230, GSK-1349572; Hib-MenCY-TT, Hib-TT, HPV-6/11/16/18, Hydrocodone bitartrate; IC-51, Icatibant acetate, Imatinib mesylate, Immunoglobulin intravenous (human), Indetanib, Influenza A (H1N1) 2009 Monovalent Vaccine, Inhalable human insulin, Insulin glargine, Insulin glulisine, Interferon-beta, Ispinesib mesylate, Ixabepilone; Laromustine, Latanoprost/timolol maleate, L-Citrulline, Lenalidomide, Lexatumumab, Linezolid, Lopinavir/ritonavir, Lutropin alfa; Mapatumumab, MDX-066, MDX-1388, Mepolizumab, Methoxy polyethylene glycol-epoetin-beta, Metreleptin, Micafungin sodium, Mometasone furoate/oxymetazoline hydrochloride, Mx-dnG1, Mycophenolic acid sodium salt; Nabiximols, Natalizumab

  15. Clinical Effect and Safety Profile of Recombinant Human Lysosomal Acid Lipase in Patients with Cholesteryl Ester Storage Disease

    PubMed Central

    Balwani, Manisha; Breen, Catherine; Enns, Gregory M; Deegan, Patrick B; Honzík, Tomas; Jones, Simon; Kane, John P; Malinova, Vera; Sharma, Reena; Stock, Eveline O; Valayannopoulos, Vassili; Wraith, J Edmond; Burg, Jennifer; Eckert, Stephen; Schneider, Eugene; Quinn, Anthony G

    2013-01-01

    Background & Aims Cholesteryl Ester Storage Disease, an inherited deficiency of lysosomal acid lipase, is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. Methods To assess the clinical effects and safety of the recombinant human lysosomal acid lipase, sebelipase alfa, 9 patients received 4 once-weekly infusions (0.35, 1, or 3 mg·kg−1) in LAL-CL01 which is the first human study of this investigational agent. Patients completing LAL-CL01 were eligible to enroll in the extension study (LAL-CL04) in which they again received 4 once-weekly infusions of sebelipase alfa (0.35, 1, or 3 mg·kg−1) before transitioning to long term every other week infusions (1 or 3 mg·kg−1). Results Sebelipase alfa was well-tolerated with mostly mild adverse events unrelated sebelipase alfa. No anti-drug antibodies were detected. Transaminases decreased in patients in LAL-CL01 and increased between studies. In 7 patients receiving ongoing sebelipase alfa treatment in LAL-CL04, mean±SD decreases for alanine transaminase and aspartate aminotransferase at week 12 compared to the baseline values in LAL-CL01 were 46±21U/L (-52%) and 21±14U/L (-36%), respectively (p<0.05). Through week 12 of LAL-CL04, these 7 patients also showed mean decreases from baseline in total cholesterol of 44±41mg/dL (-22%; p=0.047), low density lipoprotein-cholesterol of 29±31mg/dL (-27%; p=0.078), and triglycerides of 50±38mg/dL (-28%, p=0.016) and increases in high density lipoprotein-cholesterol of 5mg/dL (15%; p=0.016). Conclusions These data establish that sebelipase alfa, an investigational enzyme replacement, in patients with Cholesteryl Ester Storage Disease is well tolerated, rapidly decreases serum transaminases and that these improvements are sustained with long term dosing and are accompanied by improvements in serum lipid profile. PMID:23348766

  16. Intravenous Erythropoietin in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Najjar, Samer S.; Rao, Sunil V.; Melloni, Chiara; Raman, Subha V.; Povsic, Thomas J.; Melton, Laura; Barsness, Gregory W.; Prather, Kristi; Heitner, John F.; Kilaru, Rakhi; Gruberg, Luis; Hasselblad, Vic; Greenbaum, Adam B.; Patel, Manesh; Kim, Raymond J.; Talan, Mark; Ferrucci, Luigi; Longo, Dan L.; Lakatta, Edward G.; Harrington, Robert A.

    2012-01-01

    Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients Prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single-dose (60,000 units of epoetin alfa) efficacy phase involving 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Intervention Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. Main Outcome Measure Infarct size, expressed as a percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging 2–6 days after study medication administration. Results In the efficacy cohort (n=138), infarct size did not differ between groups at either 2–6 days (15.8±10.3 vs. 15.0±10.0, P=.666) or 12±2 weeks (10.6±8.6 vs. 10.4±7.6, P=.886). Left ventricular ejection fraction also did not differ between groups at either the early (48.2±9.1 vs. 48.9±8.7, P=.671) or late (52.5±9.3 vs. 52.0±8.8, P=.760) timepoints. In pre-specified analyses of patients aged ≥70 years (n=21), mean infarct size within the first week was larger in the epoetin alfa arm than in the placebo group (19.9±9.9 vs.11.7±7.2, P=.026). Patients who received epoetin alfa had a higher incidence of the composite endpoint of death, myocardial infarction, stroke, or stent thrombosis (4.0% vs. 0.0%, P=.042), and a higher incidence of serious adverse events (20.0% vs. 10.3%, P=.052). Conclusions In STEMI patients successfully reperfused with primary or rescue PCI, a single intravenous bolus of epoetin alfa did not reduce infarct size and was

  17. Half-life extended factor VIII for the treatment of hemophilia A.

    PubMed

    Tiede, A

    2015-06-01

    Prophylactic infusion of factor VIII (FVIII) prevents joint bleeding and other hemorrhages in patients with hemophilia A. Conventional FVIII concentrates have a short half-life, with an average of about 12 h in adults, ranging in individual patients between 6 and 24 h, and even shorter in younger children. Therefore, effective prophylaxis requires frequent intravenous injection, usually three times per week or every other day. Several technologies are currently under investigation to extend the half-life of FVIII, including Fc fusion (Eloctate, Elocta, efmoroctocog alfa), addition of polyethylene glycol (turoctocog alfa pegol [N8-GP], BAY 94-9027, BAX 855), and a single-chain construct (CSL627). This review summarizes characteristics of products in clinical development and discusses their potential benefits.

  18. Sofosbuvir for treatment of chronic hepatitis C.

    PubMed

    Kattakuzhy, Sarah; Levy, Rachel; Kottilil, Shyam

    2015-04-01

    Chronic hepatitis C is a leading cause of liver-related morbidity and mortality worldwide. If untreated, chronic hepatitis C can progress to advanced liver fibrosis, cirrhosis, liver failure, hepatocellular carcinoma and death. Until recently, treatment of hepatitis C predominantly constituted an immunomodulatory agent, peg-interferon-alfa and ribavirin. In 2011, the first class of directly acting antiviral agents, HCV NS3/4A serine protease inhibitors, was added to peg-interferon-alfa and ribavirin with increased efficacy. In the past year, an NS5B inhibitor, sofosbuvir, has emerged as a potent agent with pangenotypic efficacy, resulting in the first interferon-free regimen for the treatment of hepatitis C. This review summarizes the data that resulted in regulatory approval of sofosbuvir and highlights the future of hepatitis C therapy with sofosbuvir as the backbone of a highly effective antiviral regimen.

  19. Isoprenoids emission in Stipa tenacissima L.: Photosynthetic control and the effect of UV light.

    PubMed

    Guidolotti, Gabriele; Rey, Ana; Medori, Mauro; Calfapietra, Carlo

    2016-01-01

    Fluxes of CO2 and isoprenoids were measured for the first time in Stipa tenacissima L (alfa grass), a perennial tussock grass dominant in the driest areas of Europe. In addition, we studied how those fluxes were influenced by environmental conditions, leaf ontogeny and UV radiation and compared emission rates in two contrasting seasons: summer when plants are mostly inactive and autumn, the growing season in this region. Leaf ontogeny significantly affected both photosynthesis and isoprenoids emission. Isoprene emission was positively correlated with photosynthesis, although a low isoprene emission was detected in brown leaves with a net carbon loss. Moreover, leaves with a significant lower photosynthesis emitted only monoterpenes, while at higher photosynthetic rates also isoprene was produced. Ambient UV radiation uncoupled photosynthesis and isoprene emission. It is speculated that alfa grass represent an exception from the general rules governing plant isoprenoid emitters.

  20. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  1. Mechanism of action of guanfacine: a postsynaptic differential approach to the treatment of attention deficit hyperactivity disorder (adhd).

    PubMed

    Alamo, Cecilio; López-Muñoz, Francisco; Sánchez-García, Javier

    2016-05-01

    The treatment of ADHD has focused on the use of psychostimulants drugs such as methylphenidate or amphetamine and derivatives, or not stimulants agents, such as atomoxetine. These agents act mainly on catecholaminergic presynaptic mechanisms. Recently the European Medicines Agency (EMA) has approved another not psychostimulant drug, guanfacine extended release (ER), as a new option to the treatment of ADHD, which acts at postsynaptic level. Guanfacine stimulates postsynaptic alfa-2A adrenergic receptors so it inhibits the production of cAMP and closes HCN channels enhancing the effectiveness of the signal of the pyramidal neurons of the prefrontal cortex (PFC), thus improving working memory and attention. In addition, stimulation of the alpha-2A receptors promotes growth and maturation of the dendritic spines of pyramidal neurons of the medial PFc, that are associated with brain function such as learning and memory. In contrast with psychostimulants or atomoxetine, guanfacine mimics noradrenaline stimulation of postsynaptic receptors alfa-2A on the PFC. PMID:27254403

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-04-01

    Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, AMA1-C1/alhydrogel, Amlodipine besylate/atorvastatin calcium, Aripiprazole, Artesunate/amodiaquine, Asenapine maleate; Bosentan, Brivaracetam; Carisbamate, Clevudine, Clofarabine, Corticorelin acetate; Dasatinib; Elinogrel potassium, Entecavir, Erlotinib hydrochloride, Eslicarbazepine acetate, Etazolate; Fampridine, Fluarix, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, GDC-0941, GI-5005, Golimumab; Imatinib mesylate, Lacosamide, Lapatinib ditosylate, Levetiracetam, Liraglutide, LOLA; Mecasermin, Morphine hydrochloride; Natalizumab, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Poly I:CLC, Pralatrexate, Pregabalin; Ranolazine, Rasagiline mesilate, Retigabine hydrochloride, Rhenium Re-186 etidronate, Rosuvastatin calcium, Rotigotine, RTL-1000, Rufinamide; Sirolimus-eluting coronary stent, Sirolimus-eluting stent, Sorafenib, Stiripentol; Tiotropium bromide; Valsartan/amlodipine besylate, Varenicline tartrate; XL-184; Zoledronic acid monohydrate. PMID:20448862

  3. Results from the Arecibo Galactic HI Survey (GALFA-HI)

    NASA Astrophysics Data System (ADS)

    Begum, Ayesha; Ballering, N.; Stanimirovic, S.; Douglas, K.; Gibson, S. J.; Grcevich, J.; Heiles, C.; Korpela, E.; Lee, M.; Peek, J. E. G.; Putman, M. E.

    2009-12-01

    The consortium for Galactic studies with the Arecibo L-band Feed Array (ALFA) is conducting a neutral hydrogen survey of the whole Arecibo sky (declination range from -1 to 38 deg), over a velocity range of -700 to +700 km/s, with high angular (3.5 arcmin) and velocity resolution (0.2 km/s). We present highlights from TOGS (Turn On GALFA Survey), the largest portion of GALFA-HI, which is covering thousands of square degrees in commensal drift scan observations with the ALFALFA and AGES extragalactic ALFA surveys. The unprecedented resolution and sensitivity of our survey resulted in the detection of numerous isolated, ultra-compact HI clouds at low Galactic velocities, which are distinctly separated from the HI disk emission. We will discuss properties of this population, and their role in the interplay between the Galactic disk and halo.

  4. Hematopoietic management in oncology practice. Part 2. Erythropoietic factors.

    PubMed

    Glaspy, John A

    2003-12-01

    As the major regulator of erythropoiesis in man, erythropoietin inhibits the programmed cell death of committed erythroid precursors. In cancer patients, a relative erythropoietin deficiency is coupled with a decreased responsiveness to the substance mediated by the effects of inflammatory cytokines on the marrow and on ferrokinetics, leading to a high incidence of anemia. Two recombinant human erythropoietin (rhEPO) preparations--epoetin alfa (Epogen, Procrit) and epoetin beta (Marogen)--as well as a modified erythropoietic compound (darbepoetin alfa [Aranesp]) are in clinical use. Part 2 of this two-part series on hematopoietic agents reviews the use of these erythropoietic factors and their effect on the anemia that develops in cancer patients. Thrombopoietic factors and progenitor cell-mobilizing factors are also briefly addressed. PMID:14723012

  5. 21 Cm Tomography With the Alfalfa Survey

    NASA Astrophysics Data System (ADS)

    Fry, Alexander B.; Boutan, C.; Carroll, P. A.; Hazelton, B.; Morales, M. F.

    2011-01-01

    Neutral hydrogen (HI) 21cm intensity mapping, or HI tomography is a promising technique being utilized by several upcoming experiments (LOFAR, MWA, SKA). The measurement of volume averaged neutral hydrogen mass density in synoptic sky surveys can be applied to the study of the HI mass function, the distribution of large scale structure, the reionization of the universe, and the expansion history of the universe through such standard rulers as baryonic acoustic oscillations. In order to prepare for future experiments, in particular the Murchison Widefield Array (MWA), we analyze the Arecbo Legacy Fast ALFA (Arecibo L-Band Feed Array) Feed Array (ALFALFA) survey data to probe the spatial density variations of HI in our local universe (z <0.06) where data is currently available. We address challenges unique to data of this kind, such as identifying and subtracting out signal from RFI and local galactic sources, and characterizing the ALFA array beam pattern which dictates sensitivity and resolution.

  6. Effect of pressure upon wall-to-wall polymerization contraction of a chemically-cured resin.

    PubMed

    Hansen, E K

    1983-02-01

    The marginal gaps of 105 Silar fillings were measured after application of a load between zero and 100 N on the matrix during the initial polymerization. The fillings were placed in non-etched dentin cavities in extracted human teeth. The dentin surrounding the cavities was either roughened with carborundum paper No. 220 or polished with Alfa Micropolish 1 micron before the cavities were filled. When load was applied to the matrix, no effect was found of the roughness surrounding the cavities, but without load the wall-to-wall contraction was significantly greater in cavities where the surrounding dentin surfaces had been polished with Alfa Micropolish. Apparently the effect of load was related to friction during the polymerization between filling surplus and the dentin surrounding the cavities and not to load per se.

  7. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome.

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  9. Cellulose fibers obtained by organosolv process from date palm rachis (Phoenix dactylifera L.)

    NASA Astrophysics Data System (ADS)

    Ammar, H.; Abid, M.; Abid, S.

    2012-02-01

    In this preliminary study, the chemical composition of Tunisian DPR was established and discussed. The main characteristic of this agri-residue was its high lignin content in comparison with that of alfa plant. CIMV process was used to selectively separate cellulose fibres, hemicelluloses and lignin at atmospheric pressure. The obtained unbleached pulp was analysed in accordance with Kappa index and degree of polymerisation and then bleached by treating successively with peroxyacids and hydrogen peroxide in basic media.

  10. High magnetic field facilities in Latin America

    NASA Astrophysics Data System (ADS)

    Sato, R.; Grössinger, R.; Bertorello, H.; Broto, J. M.; Davies, H. A.; Estevez-Rams, E.; Gonzalez, J.; Matutes, J.; Sinnecker, J. P.; Sagredo, V.

    2006-11-01

    The EC supported a network (under the Framework 5 ALFA Programme) designated HIFIELD (Project number II0147FI) and entitled: "Measurement methods involving high magnetic fields for advanced and novel materials". As a result, high field facilities were initiated, constructed or extended at the following laboratories in Latin America: University Cordoba (Argentina), CES, Merida (Venezuela), CIMAV, Chihuahua (Mexico), University Federal de Rio de Janeiro (Brazil).

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  13. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-09-01

    12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles

  14. Rapid progression of antiviral treatments of chronic hepatitis C virus infection.

    PubMed

    Pol, S; Corouge, M; Mallet, V; Sogni, P

    2013-06-01

    The treatment of hepatitis C virus (HCV) infection with pegylated interferon alfa and ribavirin leads to a sustained virologic response in around 50% of patients with HCV genotype 1, 65% with HCV genotype 4, 75% with HCV genotype 3 and around 80% with HCV genotype 2. A better understanding of the HCV life-cycle recently resulted in the development of several potential direct-acting antiviral drugs (DAAs) targeting viral proteins (NS3/4A protease inhibitors, NS5B nucleos(t)idic and non nucleos(t)idic polymerase inhibitors, NS5A replication complex inhibitors). A lot of data have been reported with the combinations of pegylated interferon-alfa/ribavirin and the first generation oral DAAs, Telaprevir and Boceprevir. These regimens have demonstrated a high level of antiviral efficacy and an acceptable safety profile in treatment-naïve patients and in prior non-responders to pegylated interferon-alfa/ribavirin. After this first major step, the combination of the second generation DAAs with pegylated interferon-alfa/ribavirin will impact antiviral potency and tolerance and will reduce the duration of therapies and the pill burden. The next step will be the oral combination of new DAAs which is likely to become the standard of care for chronic HCV after 2015. Most studies are conducted in small numbers of "easy-to-treat" patients with short post-treatment period for concluding to a sustained virologic response: extension of both the numbers of treated patients and post-treatment follow-up, inclusion of more difficult-to-treat patients (experienced genotype 3-infected or genotype 1-infected patients who failed to first generation protease inhibitors, cirrhotic, HIV co-infected patients, allograft recipients or candidates to transplantation) will probably reduce the overall rate of cure. PMID:23831907

  15. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome. PMID:26433845

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  18. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  1. Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

    PubMed

    Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

    2016-01-01

    We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta.

  2. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented. PMID:25648140

  3. Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

    PubMed Central

    Tomatsu, Shunji; Sawamoto, Kazuki; Shimada, Tsutomu; Bober, Michael B.; Kubaski, Francyne; Yasuda, Eriko; Mason, Robert W.; Khan, Shaukat; Alméciga-Díaz, Carlos J.; Barrera, Luis A.; Mackenzie, William G.

    2015-01-01

    Introduction Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older. Areas covered Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT. Expert opinion We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues. PMID:26973801

  4. The modelling of symmetric airfoil vortex generators

    NASA Technical Reports Server (NTRS)

    Reichert, B. A.; Wendt, B. J.

    1996-01-01

    An experimental study is conducted to determine the dependence of vortex generator geometry and impinging flow conditions on shed vortex circulation and crossplane peak vorticity for one type of vortex generator. The vortex generator is a symmetric airfoil having a NACA 0012 cross-sectional profile. The geometry and flow parameters varied include angle-of-attack alfa, chordlength c, span h, and Mach number M. The vortex generators are mounted either in isolation or in a symmetric counter-rotating array configuration on the inside surface of a straight pipe. The turbulent boundary layer thickness to pipe radius ratio is delta/R = 0. 17. Circulation and peak vorticity data are derived from crossplane velocity measurements conducted at or about 1 chord downstream of the vortex generator trailing edge. Shed vortex circulation is observed to be proportional to M, alfa, and h/delta. With these parameters held constant, circulation is observed to fall off in monotonic fashion with increasing airfoil aspect ratio AR. Shed vortex peak vorticity is also observed to be proportional to M, alfa, and h/delta. Unlike circulation, however, peak vorticity is observed to increase with increasing aspect ratio, reaching a peak value at AR approx. 2.0 before falling off.

  5. Mechanical Properties of Aluminum Matrix Composite Reinforced by Carbothermally Reduced of Fly Ash

    SciTech Connect

    Jamasri; Wildan, M. W.; Sulardjaka; Kusnanto

    2011-01-17

    The addition of fly ash into aluminum as reinforcement can potentially reduce the production cost and density of aluminum. However, mechanical properties of aluminum matrix composite reinforced by fly ash (MMC ALFA) have some limitations due to the characteristic of fly ash. In this study, a carbothermal reduction process of fly ash and activated carbon powder with particle size <32 {mu}m was performed prior to produce MMC ALFA.The process was carried out in a furnace at 1300 deg. C in vacuum condition under argon flow. Synthesis product was analyzed by XRD with Cu-K{sub {alpha}} radiation. From XRD analysis, it shows that the synthesis process can produce SiC powder. The synthesis product was subsequently used as reinforcement particle. Aluminum powder was mixed with 5, 10 and 15% of the synthesized powder, and then uni-axially compacted at pressure of 300 MPa. The compacted product was sintered for 2 hours in argon atmosphere at temperature variation of 550 and 600 deg. C. Flexural strength, hardness and density of MMC ALFA's product were respectively evaluated using a four point bending test method based on ASTM C1161 standard, Brinell hardness scale and Archimedes method. The result of this study shows that the increase of weight of reinforcement can significantly increase the hardness and flexural strength of MMCs. The highest hardness and flexural strength of the MMC product are 300 kg/mm{sup 2} and 107.5 MPa, respectively.

  6. Erythropoiesis-stimulating agents in renal medicine.

    PubMed

    Locatelli, Francesco; Del Vecchio, Lucia

    2011-01-01

    The four currently available erythropoiesis-stimulating agents (ESAs), the main drugs for correcting anemia in patients with chronic kidney disease (CKD), are epoetin alfa, epoetin beta, darbepoetin alfa, and continuous erythropoietin receptor activator. The last two have much longer half-lives, which means they can be administered less frequently. The expiry of the patents for epoetin alfa and epoetin beta some years ago opened up the way for the production of a number of biosimilars that are now marketed in the European Union. Because biosimilars cannot be identical to their originator, a complex and still-evolving regulatory policy has been generated, but there are still a number of issues concerning international naming, automatic substitution, and safety. All ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. Following the publication of a number of trials indicating no benefit (and even possible harm) when ESAs are used to aim at near-normal hemoglobin levels in CKD patients, the hemoglobin target has become a major subject of discussion. According to the position statement of the Anemia Group of the European Renal Best Practice, it should generally be about 11-12 g/dL; however, a risk-benefit evaluation is warranted in individual patients, and high ESA doses driven by hyporesponsiveness should be avoided.

  7. Achieving therapeutic targets in renal anaemia: considering cost-efficacy.

    PubMed

    Deray, Gilbert

    2004-07-01

    Erythropoietin treatment for anaemia in chronic kidney disease (CKD) brings important clinical benefits, but restricted healthcare budgets necessitate value-for-money therapies, requiring economic considerations also to be taken into account when selecting a treatment regimen. Subcutaneous (s.c.) administration of epoetin is effective at a lower dose than intravenous (i.v.) administration, offering the potential for substantial reductions in costs of treatment. Unlike epoetin alfa, which is contra-indicated by the s.c. route in Europe in patients with CKD, epoetin beta (NeoRecormon) can be safely and effectively given by either route. The multidose presentations of epoetin beta (Reco-Pen, multidose vials) may provide further opportunity for dose reduction. The tolerability of s.c. epoetin beta is excellent and superior compared with epoetin alfa or darbepoetin alfa. Epoetin beta given once weekly is as effective as two- or three-times weekly, and the dosing frequency can be further reduced to once every 2 weeks in patients who are stable on once-weekly dosing. Reduced dosing frequency is more convenient for the patient and may save nursing time in dialysis units. Overall, s.c. epoetin beta, compared with alternative treatments, may represent a cost-effective treatment option for anaemia management as it combines a well-established safety and efficacy record, favourable local tolerability, and the convenience of once-weekly dosing with the potential to reduce treatment costs by up to 30%. PMID:15265254

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

    (+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19649342

  9. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-09-01

    Aclidinium bromide, AE-37, Alemtuzumab, AMA1-C1/ISA 720, Amlodipine besylate/atorvastatin calcium, Arachidonic acid, Arbaclofen placarbil, Aripiprazole, ARQ-621, Azelnidipine, Azilsartan medoxomil potassium; Bevacizumab, Biphasic insulin aspart, Bortezomib; Choriogonadotropin alfa, CTS-1027; Dapagliflozin, Dasatinib, Deforolimus, Degarelix acetate, Denufosol tetrasodium, Desvenlafaxine succinate, Dronedarone hydrochloride, Duloxetine hydrochloride, Dutasteride; Enfuvirtide, Entecavir, Etaracizumab, Everolimus, Exenatide, Ezetimibe; Ferric carboxymaltose, Fludarabine, Foretinib; Gefitinib, GFT-505, GSK-256066; HPV-6/11/16/18, HuM195/rGel, HyperAcute-Lung cancer vaccine; I5NP, Imatinib mesylate, Imexon, Insulin detemir, Insulin glargine, Ivabradine hydrochloride; L2G7, Lacosamide, Lapatinib ditosylate, Lenalidomide, Lidocaine/prilocaine, Liposomal vincristine, Liraglutide, Lixivaptan; Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine, Methoxy polyethylene glycol-epoetin-β, Mirabegron, Morphine/oxycodone, MR Vaccine, MSC-1936369B, Mycophenolic acid sodium salt; Narlaprevir, N-Desmethylclozapine; Ocriplasmin, Olaparib, Olmesartan medoxomil, Olmesartan medoxomil/azelnidipine, ONO-5334, ONO-8539; Palifermin, Panitumumab, Pardoprunox hydrochloride, PCV7, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pexelizumab, PF-337210, Pitavastatin calcium; Raltegravir potassium, Recombinant interleukin-7, Regadenoson, Reniale, Roflumilast, Rosuvastatin calcium; Safinamide mesilate, SB-1518, SCH-527123, Selumetinib, Sipuleucel-T, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talaporfin sodium, Tanespimycin, Technosphere/Insulin, Telaprevir, Telatinib, Telcagepant, Telmisartan/hydrochlorothiazide, Teriparatide, Testosterone transdermal gel, TH-302, Tiotropium bromide, Tocilizumab, Trabedersen, Tremelimumab; Valsartan/amlodipine besylate, Vernakalant hydrochloride, Visilizumab, Voreloxin, Vorinostat. PMID

  10. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients.

    PubMed

    Laguno, Montserrat; Martínez-Rebollar, Maria; Perez, Iñaki; Costa, Josep; Larrousse, Maria; Calvo, Marta; Loncá, Montse; Muñoz, Ana; González-Cordón, Ana; Blanco, José Luís; Martínez, Esteban; Gatell, Josep Maria; Mallolas, Josep

    2012-10-01

    Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results. PMID:22428909

  11. Mechanical Properties of Aluminum Matrix Composite Reinforced by Carbothermally Reduced of Fly Ash

    NASA Astrophysics Data System (ADS)

    Jamasri, Wildan, M. W.; Sulardjaka, Kusnanto

    2011-01-01

    The addition of fly ash into aluminum as reinforcement can potentially reduce the production cost and density of aluminum. However, mechanical properties of aluminum matrix composite reinforced by fly ash (MMC ALFA) have some limitations due to the characteristic of fly ash. In this study, a carbothermal reduction process of fly ash and activated carbon powder with particle size <32 μm was performed prior to produce MMC ALFA. The process was carried out in a furnace at 1300° C in vacuum condition under argon flow. Synthesis product was analyzed by XRD with Cu-Kα radiation. From XRD analysis, it shows that the synthesis process can produce SiC powder. The synthesis product was subsequently used as reinforcement particle. Aluminum powder was mixed with 5, 10 and 15% of the synthesized powder, and then uni-axially compacted at pressure of 300 MPa. The compacted product was sintered for 2 hours in argon atmosphere at temperature variation of 550 and 600° C. Flexural strength, hardness and density of MMC ALFA's product were respectively evaluated using a four point bending test method based on ASTM C1161 standard, Brinell hardness scale and Archimedes method. The result of this study shows that the increase of weight of reinforcement can significantly increase the hardness and flexural strength of MMCs. The highest hardness and flexural strength of the MMC product are 300 kg/mm2 and 107.5 MPa, respectively.

  12. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  13. Onset of Celiac Disease after Treatment of Chronic Hepatitis C with Interferon Based Triple Therapy

    PubMed Central

    Singh, Amandeep; Zaeri, Nayere; Ho, Immanuel K.

    2015-01-01

    Background. Patients treated with interferon (IFN) based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD) as a result of triple therapy (interferon, ribavirin, and boceprevir) for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy. PMID:26664772

  14. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  15. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  16. Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

    PubMed

    Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

    2001-02-01

    Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler. PMID:11334124

  17. Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V)

    NASA Astrophysics Data System (ADS)

    El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

    2007-04-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at λmax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 μg mL -1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method.

  18. Structure, conformation and hydrogen bonding of 4-( N-methylpiperidinium)-butyric acid bromide

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Z.; Dulewicz, E.; Szafran, M.; Thaimattam, R.; Jaskolski, M.

    2007-02-01

    A 1:1 complex between 4-( N-methylpiperidinium)-butyrate inner salt (betaine) and hydrobromide, MPBUH·Br, has been characterized by single crystal X-ray analysis. The crystals are monoclinic, space group P2 1/c, with a = 8.284(1), b = 10.369(1), c = 13.809(2) Å, β = 92.26(1)°. The piperidine ring adopts a chair conformation with the (CH 2) 3COOH substituent in the axial and the CH 3 group in the equatorial positions. In the crystal, the Br - anion is engaged in a medium-strong hydrogen bond with the COOH group (O sbnd H⋯Br - = 3.141(1) Å), N +⋯Br - electrostatic interactions and in several C sbnd H⋯Br - contacts with the aliphatic groups forming a cavity in which it is enclosed. Three conformers ( 2- 4) were optimized by the B3LYP/6-31G (d, p) level of theory. The most stable is conformer 4 with the (CH 2) 3COOH substituent in the equatorial position and the CH 3 group in the axial position. The stability of the investigated conformers is controlled by electrostatic interactions between the oppositely charged groups. The FTIR spectrum of MPBUH·Br shows a strong band at 2941 cm -1 due to νOH and the νC dbnd O band at 1712 cm -1.

  19. [Induction of rat hepatic CYP2E1 expression by arecoline in vivo].

    PubMed

    Huang, Xiang-tao; Xiao, Run-mei; Wang, Ming-feng; Wang, Jun-jun; Chen, Yong

    2016-01-01

    The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human. PMID:27405178

  20. Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.

    PubMed

    Boussès, Christine; Ferey, Ludivine; Vedrines, Elodie; Gaudin, Karen

    2015-11-10

    An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product. PMID:26183807

  1. The behaviour of trypsin towards alpha-N-methyl-alpha-N-toluene-p-sulfonyl-L-lysine beta-naphthyl ester. A new method for determining the absolute molarity of solutions of trypsin.

    PubMed

    Elmore, D T; Smyth, J J

    1968-03-01

    1. alpha-N-Methyl-alpha-N-toluene-p-sulphonyl-l-lysine beta-naphthyl ester (MTLNE) was synthesized as its hydrobromide and shown to be slowly hydrolysed by bovine pancreatic trypsin. The acylation step, however, is so much faster than deacylation of the acyl-enzyme that spectrophotometric measurement of the ;burst' of beta-naphthol provides a convenient method for determining the absolute molarity of trypsin solutions. 2. By using the same stock solution of trypsin, application of this method at pH4.0 and pH7.0 as well as that of Bender et al. (1966) at pH3.7 gave concordant results. 3. Provided that [S](0)>[E](0), the size of the ;burst' is independent of substrate concentration. 4. In the trypsin-catalysed hydrolysis of alpha-N-toluene-p-sulphonyl-l-arginine methyl ester, MTLNE functions as a powerful non-competitive inhibitor. 5. There is no detectable reaction between MTLNE and either bovine pancreatic alpha-chymotrypsin at pH4.0 or bovine thrombin at pH6.0.

  2. Preparation of a β-Cyclodextrin-Based Open-Tubular Capillary Electrochromatography Column and Application for Enantioseparations of Ten Basic Drugs.

    PubMed

    Fang, Linlin; Yu, Jia; Jiang, Zhen; Guo, Xingjie

    2016-01-01

    An open-tubular capillary electrochromatography column was prepared by chemically immobilized β-cyclodextrin modified gold nanoparticles onto new surface with the prederivatization of (3-mercaptopropyl)-trimethoxysilane. The synthesized nanoparticles and the prepared column were characterized by transmission electron microscopy, scanning electron microscopy, infrared spectroscopy and ultraviolet visible spectroscopy. When the column was employed as the chiral stationary phase, no enantioselectivity was observed for ten model basic drugs. So β-cyclodextrin was added to the background electrolyte as chiral additive to expect a possible synergistic effect occurring and resulting in a better separation. Fortunately, significant improvement in enantioselectivity was obtained for ten pairs of drug enantiomers. Then, the effects of β-cyclodextrin concentration and background electrolyte pH on the chiral separation were investigated. With the developed separation mode, all the enantiomers (except for venlafaxine) were baseline separated in resolutions of 4.49, 1.68, 1.88, 1.57, 2.52, 2.33, 3.24, 1.63 and 3.90 for zopiclone, chlorphenamine maleate, brompheniramine maleate, dioxopromethazine hydrochloride, carvedilol, homatropine hydrobromide, homatropine methylbromide, venlafaxine, sibutramine hydrochloride and terbutaline sulfate, respectively. Further, the possible separation mechanism involved was discussed. PMID:26771454

  3. [Rapid identification 15 effective components of anti common cold medicine with MRM by LC-MS/MS].

    PubMed

    Jiang, Jian-Guo; Zhang, Xi-Ru; Zhang, Yi-Hua; Song, Geng-Shen

    2013-01-01

    This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine. PMID:23600148

  4. Isolation and characterization of degradation products of citalopram and process-related impurities using RP-HPLC.

    PubMed

    Rao, Ramisetti Nageswara; Raju, Ale Narasa; Narsimha, Ramaram

    2008-06-01

    A reversed-phase high-performance liquid chromatographic method for simultaneous separation and determination of citalopram hydrobromide and its process impurities in bulk drugs and pharmaceutical formulations was developed. The separation was accomplished on an Inertsil ODS 3V (250x4.6 mm; particle size 5 mum) column using 0.3% diethylamine (pH = 4.70) and methanol/acetonitrile (55:45 v/v) as mobile phase in a gradient elution mode. The eluents were monitored by a photodiode array detector set at 225 nm. The chromatographic behavior of all the related substances was examined under variable conditions of different solvents, buffer concentrations, and pH. The method was validated in terms of accuracy, precision, and linearity. The method could be of use not only for rapid and routine evaluation of the quality of citalopram in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations. Three unknown impurities were consistently observed during the analysis of different batches of citalopram. Forced degradation of citalopram was carried out under thermal, photo, acidic, alkaline, and peroxide conditions. The degradation products and unknown impurities were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR spectroscopy.

  5. Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA

    SciTech Connect

    McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Schneider, R.D.; Lyons, B.; Roskopf, M.; Zapf-Longo, C.; Whaley, D.

    1986-04-01

    Dextrans with average molecular weights of 5000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected (/sup 99m/Tc)DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect.

  6. Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production.

    PubMed Central

    Larghi, O P; Nebel, A E

    1980-01-01

    The inactivation dynamics of rabies virus (PV strain) by binary ethylenimine, and the immunogenic properites and the stability of the vaccines prepared using this agent, were studied. Binary ethylenimine at a final concentration of 0.01 M was prepared wtih 2-bromoethylamine hydrobromide in alkaline solutions, either separately from or in suspensions of rabies virus propagated in BHK cells. The infectivity of virus suspensions containing more than 108 plaque-forming units per 0.1 ml was inactivated in 2 h when the inactivating agent was prepared before its addition to the suspensions, and in3 h when prepared directly in the suspensions. Liquid vaccines prepared in this manner and stored at different temperatures maintained potency for 1 month at 37 degrees C and for 6 months at 4 degrees C and 22 to 25 degrees C. Lyophilized vaccine maintained its potency for 6 months at the three temperatures. The inactivated vaccine mixed with aluminum or oil adjuvant at high dilutions protected guinea pigs against challenge. This safer procedure for rabies virus inactivation offers promise for the production of effective vaccines for the immunization of dogs and cattle. PMID:7358836

  7. Multi-residue method for detecting coccidiostats at carry-over level in feed by HPLC-MS/MS.

    PubMed

    Delahaut, Ph; Pierret, G; Ralet, N; Dubois, M; Gillard, N

    2010-06-01

    A multi-residue HPLC-ESI-MS/MS method has been developed for the simultaneous extraction, detection and confirmation of the 11 coccidiostats referenced by Regulation 2009/8/EC (lasalocid sodium, narasin, salinomycin sodium, monensin sodium, semduramicin sodium, maduramicin ammonium alpha, robenidine hydrochloride, decoquinate, halofuginone hydrobromide, nicarbazin, and diclazuril) in feedstuffs at carry-over level. The sensitivity of the method allows quantification and confirmation for all coccidiostats below target concentration. The method was in-house validated and meets all criteria of European legislation (2002/657/EC). The precision of the method was determined under repeatability and within-laboratory reproducibility conditions; RSD(r) and RSD(R) were below the maximum permitted values for every tested concentration. The specificity was checked by analysing representative blank samples and blank samples fortified with potentially interfering substances (benzimidazoles, corticosteroides, triphenylmethane dyes, quinolones, nitrofurans, nitroimidazoles, phenicols); no interference were found. Concerning quantification, a quadratic regression model was fitted to every calibration curve with a regression coefficient r2 above 0.99 on each data set. Finally, the expanded uncertainty U was calculated with data obtained within the laboratory while applying the method during validation and in routine tests.

  8. The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

    PubMed

    Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

    2015-08-21

    The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties.

  9. Isolation and characterization of degradation products of citalopram and process-related impurities using RP-HPLC.

    PubMed

    Rao, Ramisetti Nageswara; Raju, Ale Narasa; Narsimha, Ramaram

    2008-06-01

    A reversed-phase high-performance liquid chromatographic method for simultaneous separation and determination of citalopram hydrobromide and its process impurities in bulk drugs and pharmaceutical formulations was developed. The separation was accomplished on an Inertsil ODS 3V (250x4.6 mm; particle size 5 mum) column using 0.3% diethylamine (pH = 4.70) and methanol/acetonitrile (55:45 v/v) as mobile phase in a gradient elution mode. The eluents were monitored by a photodiode array detector set at 225 nm. The chromatographic behavior of all the related substances was examined under variable conditions of different solvents, buffer concentrations, and pH. The method was validated in terms of accuracy, precision, and linearity. The method could be of use not only for rapid and routine evaluation of the quality of citalopram in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations. Three unknown impurities were consistently observed during the analysis of different batches of citalopram. Forced degradation of citalopram was carried out under thermal, photo, acidic, alkaline, and peroxide conditions. The degradation products and unknown impurities were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR spectroscopy. PMID:18481321

  10. Determination and pharmacokinetic studies of arecoline in dog plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Bing; Zhou, Xu-Zheng; Li, Jian-Yong; Yang, Ya-Jun; Niu, Jian-Rong; Wei, Xiao-Juan; Liu, Xi-Wang; Li, Jin-Shan; Zhang, Ji-Yu

    2014-10-15

    A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arecoline concentration in dog plasma. Plasma sample was prepared by protein precipitation using n-hexane (containing 1% isoamyl alcohol) with β-pinene as an internal standard. Chromatographic separation was achieved on an Agilent C18 column (4.6×75mm, 3.5μm) using methanol: 5mM ammonium acetate as the mobile phase with isocratic elution. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve for arecoline was linear over a concentration range of 2-500ng/mL. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±10% at all concentrations. In summary, the LC-MS/MS method described herein was fully validated and successfully applied to the pharmacokinetic study of arecoline hydrobromide tablets in dogs after oral administration. PMID:25140901

  11. X-ray diffraction studies of intercalation compounds prepared from aniline salts and montmorillonite by a mechanochemical processing

    NASA Astrophysics Data System (ADS)

    Yoshimoto, Shoji; Ohashi, Fumihiko; Kameyama, Tetsuya

    2005-11-01

    Inorganic-organic intercalation compounds comprised of montmorillonite (MMT) and aniline salts with different counter anions were prepared by a mechanochemical processing. The intercalation process and the formed structure of intercalation compounds were investigated via X-ray diffraction analysis. The amounts of intercalated species were very likely dependent on the types of counter anions and increased with decreasing the size of counter anions during the mechanochemical processing. Very interestingly, much larger interlayer expansions of 1.51 nm was observed for aniline hydrofluoride AnF- and aniline hydrochloride AnCl-MMT systems in higher intercalates loading levels, suggesting that neutral guest molecules also introduce within the interlayer regions together with anilinium cations by van der Waals interactions. Judging from the larger interlayer expansions and the size of guest molecules, intercalated species are expected to prefer a tri-molecular layer arrangement with their aromatic rings perpendicular to the silicate sheets. In contrast, for aniline hydrobromide AnBr-MMT, the interlayer expansion was ca. 0.52 nm, which reveals that only anilinium cations are introduced by ion exchange and they probably adopt a vertical orientation in the interlayers. It is inferred that aniline hydroiodide AnI-MMT compounds have a heterogeneous structure containing both anilinium and sodium cations in the interlayers. Different intercalation behaviors during the mechanochemical processing strongly suggest the smaller the size of counter anions, the more guest molecules can be intercalated into the confined clay interlayers in highly ordered arrangements.

  12. Binding of benzo(a)pyrene to DNA by cytochrome P-450 catalyzed one-electron oxidation in rat liver microsomes and nuclei

    SciTech Connect

    Cavalieri, E.L.; Rogan, E.G.; Devanesan, P.D.; Cremonesi, P. ); Cerny, R.L.; Gross, M.L. ); Bodell, W.J. )

    1990-05-22

    To investigate whether cytochrome P-450 catalyzes the covalent binding of substrates to DNA by one-electron oxidation, the ability of both uninduced and 3-methylcholanthrene (MC) induced rat liver microsomes and nuclei to catalyze covalent binding of benzo(a)pyrene (BP) to DNA and formation of the labile adduct 7-(benzo(a)pyren-6-yl)guanine (BP-N7Gua) was investigated. In the various systems studied, 1-9 times more BP-N7Gua adduct was isolated than the total amount of stable BP adducts in the DNA. The specific cytochrome P-450 inhibitor 2-((4,6-dichloro-o-biphenyl)oxy)ethylamine hydrobromide (DPEA) reduced or eliminated BP metabolism, binding of BP to DNA, and formation of BP-N7Gua by cytochrome P-450 in both microsomes and nuclei. The effects of the antioxidants cysteine, glutathione, and p-methoxythiophenol were also investigated. This study represents the first demonstration of cytochrome P-450 mediating covalent binding of substrates to DNA via one-electron oxidation and suggests that this enzyme can catalyze peroxidase-type electron-transfer reactions.

  13. Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen

    PubMed Central

    Buffa, Francesca M.; Yu, Sheng; Ebner, Daniel V.; Howarth, Alison; Folkes, Lisa K.; Budwal, Balam; Chu, Kwun-Ye; Durrant, Lisa; Muschel, Ruth J.; McKenna, W. Gillies; Higgins, Geoff S.

    2015-01-01

    Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused significant radiosensitization in cancer but not normal tissue cell lines. Other means of blocking this pathway, knockdown of thiamine transporter-1 (THTR1) or treatment with the thiamine analogue pyrithiamine hydrobromide (PyrH) caused significant tumor specific radiosensitization. There was persistent DNA damage in cells irradiated after TPK1 and THTR1 knockdown or PyrH treatment. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitization target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumor specific radiosensitization. PMID:25788274

  14. In vitro Labeling of Neural Stem Cells with Poly-L-Lysine Coated Super Paramagnetic Nanoparticles for Green Fluorescent Protein Transfection

    PubMed Central

    Albukhaty, Salim; Naderi-Manesh, Hossein; Tiraihi, Taki

    2013-01-01

    Background: The magnetic nanoparticle-based transfection method is a relatively new technique for delivery of functional genes to target tissues. We aimed to evaluate the transfection efficiency of rat neural stem cell (NSC) using poly-L-lysine hydrobromide (PLL)-coated super paramagnetic iron oxide nanoparticles (SPION). Methods: The SPION was prepared and coated with PLL as transfection agent and the transfection efficiency was evaluated in rat NSC using enhanced green fluorescent protein-N1 plasmid containing GFP as a reporter gene. NSC was incubated for 24 h in cell culture media containing 25 µg/ml SPION and in different concentrations of PLL (0.25, 0.50, 0.75, 1 and 2 µg/ml). Cell viability was determined before and after transfection for every concentration using Trypan blue assay. Characterization of prepared uncoated (SPION) and coated (SPION-PLL) complexes were evaluated by a transmission electron microscope and the zeta potential. Results: PLL at 0.75 μg/ml showed optimal results with 25 μg/ml SPION concentration compared with other PLL concentrations (0.25, 0.50, 1 and 2 μg/ml). The 18% efficiency of the transfected cells showed green fluorescence. Conclusion: Transfection with SPION is an efficient, non-viral gene transfere method. PMID:23567848

  15. Sympathetic Nervous System Control of Carbon Tetrachloride-Induced Oxidative Stress in Liver through α-Adrenergic Signaling.

    PubMed

    Lin, Jung-Chun; Peng, Yi-Jen; Wang, Shih-Yu; Lai, Mei-Ju; Young, Ton-Ho; Salter, Donald M; Lee, Herng-Sheng

    2016-01-01

    In addition to being the primary organ involved in redox cycling, the liver is one of the most highly innervated tissues in mammals. The interaction between hepatocytes and sympathetic, parasympathetic, and peptidergic nerve fibers through a variety of neurotransmitters and signaling pathways is recognized as being important in the regulation of hepatocyte function, liver regeneration, and hepatic fibrosis. However, less is known regarding the role of the sympathetic nervous system (SNS) in modulating the hepatic response to oxidative stress. Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma. Mice treated with 6-hydroxydopamine hydrobromide were used to realize chemical sympathectomy. Carbon tetrachloride (CCl4) injection was used to induce oxidative liver injury. Sympathectomized animals were protected from CCl4 induced hepatic lipid peroxidation-mediated cytotoxicity and genotoxicity as assessed by 4-hydroxy-2-nonenal levels, morphological features of cell damage, and DNA oxidative damage. Furthermore, sympathectomy modulated hepatic inflammatory response induced by CCl4-mediated lipid peroxidation. CCl4 induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist. We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.

  16. Simultaneous determination of some active ingredients in cough and cold preparations by gas chromatography, and method validation.

    PubMed

    Harsono, Thresiana; Yuwono, Mochammad; Indrayanto, Gunawan

    2005-01-01

    A simple and rapid gas chromatographic (GC) method has been developed for the simultaneous determination of combinations of acetaminophen, phenylpropanolamine hydrochloride, guaifenesin, pseudoephedrine hydrochloride, caffeine, chlorpheniramine maleate, and dextromethorphan hydrobromide in cough and cold tablets and syrups. After extraction of the analyte with alkaline ethyl acetate, 2 microL extract was injected (splitting ratio of 50:1) into a gas chromatograph equipped with a CBP1-M25-025 fused silica capillary column (25 m x 0.22 mm; film thickness, 0.25 microm). The column temperature was held at 150 degrees C for 5 min, increased to 175 degrees C at 3 degrees C/min, and increased to 270 degreesC at 10 degrees C/min. The temperatures of the flame ionization detector and injector were maintained at 300 degrees C. The GC method is inexpensive, rapid, accurate, and precise, and thus it can be used for routine analysis of tablet and syrup preparations in quality control laboratories of pharmaceutical companies. PMID:16152925

  17. Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice

    PubMed Central

    Ueki, Toshiyuki; Mizoguchi, Kazushige; Yamaguchi, Takuji; Nishi, Akinori; Ikarashi, Yasushi; Hattori, Tomohisa; Kase, Yoshio

    2015-01-01

    The traditional Japanese medicine yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of yokukansan on a 5-HT1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with yokukansan. Thereafter, the density and affinity of 5-HT1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1A receptor density or affinity. However, yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that yokukansan increases 5-HT1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects. PMID:26681968

  18. Cholinergic system, rearing environment and trajectory learning during aging in mice.

    PubMed

    Thouvarecq, R; Caston, J; Protais, P

    2007-01-30

    Three, 12- and 20-month-old C57BL6/J mice, reared in standard conditions or in enriched environments, were administered subcutaneously either scopolamine hydrobromide, 0.6 or 1.2 mg kg(-1), or physiological saline (control mice) 15 min before testing their abilities to find an invisible platform in a modified version of the Morris water maze, the starting point being kept unchanged throughout the experiment to allow the aged animals to solve the task. The results demonstrated that: 1) All control mice, whatever their age, were able to learn the platform location, but the number of trials needed to reach the learning criterion (3 consecutive trials in less than 8 s) increased with age; 2) All the scopolamine-treated mice, whatever their age, were also able to learn the platform location. However, compared to age-matched controls, the number of trials needed to reach the learning criterion was greater; 3) Rearing the animals in an enriched environment antagonized the effect of scopolamine, but only in the youngest (3 month-old) mice. All control and scopolamine-treated mice, whatever their age and their rearing environment, remembered, 7 days later, the platform location.

  19. Development and validation of a generic high-performance liquid chromatography for the simultaneous separation and determination of six cough ingredients: Robustness study on core-shell particles.

    PubMed

    Yehia, Ali Mohamed; Essam, Hebatallah Mohamed

    2016-09-01

    A generally applicable high-performance liquid chromatographic method for the qualitative and quantitative determination of pharmaceutical preparations containing phenylephrine hydrochloride, paracetamol, ephedrine hydrochloride, guaifenesin, doxylamine succinate, and dextromethorphan hydrobromide is developed. Optimization of chromatographic conditions was performed for the gradient elution using different buffer pH values, flow rates and two C18 stationary phases. The method was developed using a Kinetex® C18 column as a core-shell stationary phase with a gradient profile using buffer pH 5.0 and acetonitrile at 2.0 mL/min flow rate. Detection was carried out at 220 nm and linear calibrations were obtained for all components within the studied ranges. The method was fully validated in agreement with ICH guidelines. The proposed method is specific, accurate and precise (RSD% < 3%). Limits of detection are lower than 2.0 μg/mL. Qualitative and quantitative responses were evaluated using experimental design to assist the method robustness. The method was proved to be highly robust against 10% change in buffer pH and flow rate (RSD% < 10%), however, the flow rate may significantly influence the quantitative responses of phenylephrine, paracetamol, and doxylamine (RSD% > 10%). Satisfactory results were obtained for commercial combinations analyses. Statistical comparison between the proposed chromatographic and official methods revealed no significant difference. PMID:27404374

  20. Determination of aflatoxin B1 in baby food (infant formula) by immunoaffinity column cleanup liquid chromatography with postcolumn bromination: collaborative study.

    PubMed

    Stroka, J; Anklam, E; Joerissen, U; Gilbert, J

    2001-01-01

    A collaborative study was conducted to evaluate the effectiveness of an immunoaffinity column cleanup liquid chromatography (LC) method for determination of aflatoxin B, in a milk powder based infant formula at a possible future European regulatory limit (0.1 ng/g). The test portion was extracted with methanol-water (8 + 2 [v + v]), filtered, diluted with water, and applied to an immunoaffinity column. The column was washed with water to remove interfering compounds, and the purified aflatoxin B1 was eluted with methanol. The separation and determination of the aflatoxin B1 was performed by reversed-phase LC and detected by fluorescence after postcolumn derivatization (PCD) involving bromination. PCD was achieved with either pyridinum hydrobromide perbromide (PBPB) or an electrochemical (Kobra) cell by addition of bromide to the mobile phase. The baby food (infant formula) test samples, both spiked and naturally contaminated with aflatoxin B1, were sent to 14 laboratories in 13 different European countries. Test portions were spiked at levels of 0.1 and 0.2 ng/g for aflatoxin B1. Recoveries ranged from 101 to 92%. Based on results for spiked test samples (blind pairs at 2 levels) and naturally contaminated test samples (blind pairs at 3 levels), the relative standard deviation for repeatability (RSDr) ranged from 3.5 to 14%. The relative standard deviation for reproducibility (RSDR) ranged from 9 to 23%. Nine participants used PBPB derivatization, and PMID:11501912

  1. Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen.

    PubMed

    Tiwana, Gaganpreet S; Prevo, Remko; Buffa, Francesca M; Yu, Sheng; Ebner, Daniel V; Howarth, Alison; Folkes, Lisa K; Budwal, Balam; Chu, Kwun-Ye; Durrant, Lisa; Muschel, Ruth J; McKenna, W Gillies; Higgins, Geoff S

    2015-03-20

    Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused significant radiosensitization in cancer but not normal tissue cell lines. Other means of blocking this pathway, knockdown of thiamine transporter-1 (THTR1) or treatment with the thiamine analogue pyrithiamine hydrobromide (PyrH) caused significant tumor specific radiosensitization. There was persistent DNA damage in cells irradiated after TPK1 and THTR1 knockdown or PyrH treatment. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitization target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumor specific radiosensitization.

  2. The GABAA antagonist DPP-4-PIOL selectively antagonises tonic over phasic GABAergic currents in dentate gyrus granule cells.

    PubMed

    Boddum, Kim; Frølund, Bente; Kristiansen, Uffe

    2014-11-01

    GABAA receptors mediate two different types of inhibitory currents: phasic inhibitory currents when rapid and brief presynaptic GABA release activates postsynaptic GABAA receptors and tonic inhibitory currents generated by low extrasynaptic GABA levels, persistently activating extrasynaptic GABAA receptors. The two inhibitory current types are mediated by different subpopulations of GABAA receptors with diverse pharmacological profiles. Selective antagonism of tonic currents is of special interest as excessive tonic inhibition post-stroke has severe pathological consequences. Here we demonstrate that phasic and tonic GABAA receptor currents can be selectively inhibited by the antagonists SR 95531 and the 4-PIOL derivative, 4-(3,3-diphenylpropyl)-5-(4-piperidyl)-3-isoxazolol hydrobromide (DPP-4-PIOL), respectively. In dentate gyrus granule cells, SR 95531 was found approximately 4 times as potent inhibiting phasic currents compared to tonic currents (IC50 values: 101 vs. 427 nM). Conversely, DPP-4-PIOL was estimated to be more than 20 times as potent inhibiting tonic current compared to phasic current (IC50 values: 0.87 vs. 21.3 nM). Consequently, we were able to impose a pronounced reduction in tonic GABA mediated current (>70 %) by concentrations of DPP-4-PIOL, at which no significant effect on the phasic current was seen. Our findings demonstrate that selective inhibition of GABA mediated tonic current is possible, when targeting a subpopulation of GABAA receptors located extrasynaptically using the antagonist, DPP-4-PIOL. PMID:25103229

  3. Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.

    PubMed

    Boussès, Christine; Ferey, Ludivine; Vedrines, Elodie; Gaudin, Karen

    2015-11-10

    An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product.

  4. The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

    PubMed

    Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

    2015-08-21

    The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties. PMID:26159785

  5. Liquid chromatography and chemometric-assisted spectrophotometric methods for the analysis of two multicomponent mixtures containing cough suppressant drugs.

    PubMed

    El-Gindy, Alaa; Emara, Samy; Mesbah, Mostafa K; Hadad, Ghada M

    2005-01-01

    Three methods were applied for the analysis of 2 multicomponent mixtures containing dextromethorphan hydrobromide, phenylephrine hydrochloride, chlorpheniramine maleate, methylparaben, and propylparaben, together with either sodium benzoate (Mix 1) or ephedrine hydrochloride and benzoic acid (Mix 2). In the first method, liquid chromatography was used for their simultaneous determination using an ODS column with a mobile phase consisting of acetonitrile-phosphate buffer, pH 2.7 (40 + 60, v/v), containing 5mM heptanesulfonic acid sodium salt and ultraviolet (UV) detection at 214 nm. Also, 2 chemometric methods, principal component regression, and partial least squares were used. For both chemometric calibrations, a concentration set of the mixture consisting of each compound in each mixture was prepared in distilled water. The absorbance data in the UV spectra were measured for the 76 or 71 wavelength points in the spectral region 210-240 or 210-224 nm considering the intervals of deltagamma = 0.4 or 0.2 nm for Mix 1 and Mix 2, respectively. The 2 chemometric methods did not require any separation step. These methods were successfully applied for the analysis of the 2 multicomponent combinations in synthetic mixtures and in commercial syrups, and the results were compared with each other. PMID:16152922

  6. Pharmacological and signalling properties of a D2-like dopamine receptor (Dop3) in Tribolium castaneum.

    PubMed

    Verlinden, Heleen; Vleugels, Rut; Verdonck, Rik; Urlacher, Elodie; Vanden Broeck, Jozef; Mercer, Alison

    2015-01-01

    Dopamine is an important neurotransmitter in the central nervous system of vertebrates and invertebrates. Despite their evolutionary distance, striking parallels exist between deuterostomian and protostomian dopaminergic systems. In both, signalling is achieved via a complement of functionally distinct dopamine receptors. In this study, we investigated the sequence, pharmacology and tissue distribution of a D2-like dopamine receptor from the red flour beetle Tribolium castaneum (TricaDop3) and compared it with related G protein-coupled receptors in other invertebrate species. The TricaDop3 receptor-encoding cDNA shows considerable sequence similarity with members of the Dop3 receptor class. Real time qRT-PCR showed high expression in both the central brain and the optic lobes, consistent with the role of dopamine as neurotransmitter. Activation of TricaDop3 expressed in mammalian cells increased intracellular Ca(2+) signalling and decreased NKH-477 (a forskolin analogue)-stimulated cyclic AMP levels in a dose-dependent manner. We studied the pharmacological profile of the TricaDop3 receptor and demonstrated that the synthetic vertebrate dopamine receptor agonists, 2 - amino- 6,7 - dihydroxy - 1,2,3,4 - tetrahydronaphthalene hydrobromide (6,7-ADTN) and bromocriptine acted as agonists. Methysergide was the most potent of the antagonists tested and showed competitive inhibition in the presence of dopamine. This study offers important information on the Dop3 receptor from Tribolium castaneum that will facilitate functional analyses of dopamine receptors in insects and other invertebrates.

  7. Spectrophotometric determination of pipazethate HCl, dextromethorphan HBr and drotaverine HCl in their pharmaceutical preparations.

    PubMed

    Amin, Alaa S; El-Sheikh, Ragaa; Zahran, Faten; Gouda, Ayman Abou El-fetouh

    2007-07-01

    A simple, accurate and highly sensitive spectrophotometric method is proposed for the rapid determination of pipazethate hydrochloride, dextromethorphan hydrobromide and drotaverine hydrochloride using chromotrope 2B (C2B) and chromotrope 2R (C2R). The method consists of extracting the formed ion-associates into chloroform in the case of pipazethate HCl and dextromethorphan HBr or into methylene chloride in the case of drotaverine HCl. The ion-associates exhibit absorption maxima at 528, 540 and 532 nm with C2B and at 526, 517 and 522 nm with C2R for pipazethate HCl, dextromethorphan HBr and drotaverine HCl, respectively. The calibration curves resulting from the measurements of absorbance-concentration relations (at the optimum reaction conditions) of the extracted ion-pairs are linear over the concentration range 4.36-52.32 microg mL(-1) for pipazethate, 3.7-48.15 microg mL(-1) for dextromethorphan and 4.34-60.76 microg mL(-1) for drotaverine, respectively. The effect of acidity, reagent concentration, time, solvent and stoichiometric ratio of the ion-associates were estimated. The molar absorptivity and Sandell sensitivity of the reaction products were calculated. Statistical treatment of the results reflects that the procedure is precise, accurate and easily applied for the determination of the drugs under investigation in pure form and in their pharmaceutical preparations.

  8. Scopolamine induced deficits in a battery of rat cognitive tests: comparisons of sensitivity and specificity.

    PubMed

    Hodges, Donald Bartholomew; Lindner, Mark D; Hogan, John B; Jones, Kelly M; Markus, Etan J

    2009-05-01

    Despite much research, the cognitive effects of scopolamine hydrobromide, a cholinergic antagonist, remain controversial. Scopolamine affects multiple systems each of which can impact behavior. One way to tease apart the effects of the drug is to determine the effects of low scopolamine doses on different abilities. The present experiments compared the effects of low doses of scopolamine on a single group of rats conducting a battery of behavioral tasks: Morris water maze, radial arm maze, delayed non-matching to position tasks, and fixed ratio 5 bar pressing. The behavioral battery ranged from tasks having little cognitive demand to those thought to be based more on attention and spatial-working memory. Control experiments using additional groups of rats assessing peripheral versus central effects were conducted with both liquid and dry reinforcement and with methyl scopolamine. Furthermore, the 5-choice serial reaction time test assessed scopolamine effects on attention. The data show a wide spectrum of central and peripheral cholinergic involvement. The central effects include attention and motor initiation, both of which impact and interact with the mnemonic function of acetylcholine. These results show that a limited disruption of the central cholinergic system can have profound effects on attention and/or psychomotor control before any measurable mnemonic disruption.

  9. The synthesis of desired functional groups on PEI microgel particles for biomedical and environmental applications

    NASA Astrophysics Data System (ADS)

    Sahiner, Nurettin; Demirci, Sahin; Sahiner, Mehtap; Al-Lohedan, Hamad

    2015-11-01

    Polyethyleneimine (PEI) microgels were synthesized by micro emulsion polymerization technique and converted to positively charged forms by chemical treatments with various modifying agents with different functional groups, such as 2-bromoethanol (-OH), 4-bromobutyronitrile (-CN), 2-bromoethylamine hydrobromide (-NH2), and glycidol (-OH). The functionalization of PEI microgels was confirmed by FT-IR, TGA and zeta potential measurements. Furthermore, a second modification of the modified PEI microgels was induced on 4-bromo butyronitrile-modified PEI microgels (PEI-CN) by amidoximation, to generate new functional groups on the modified PEI microgels. The PEI and modified PEI microgels were also tested for their antimicrobial effects against various bacteria such as Bacillus subtilis ATCC 6633, Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25323. Moreover, the PEI-based particles were used for removal of organic dyes such as methyl orange (MO) and congo red (CR). The absorption capacity of PEI-based microgels increased with modification from 101.8 mg/g to 218.8 mg/g with 2-bromoethylamine, 216.2 m/g with 1-bromoethanol, and 224.5 mg/g with 4-bromobutyronitrile for MO. The increase in absorption for CR dyes was from 347.3 mg/g to 390.4 mg/g with 1-bromoethanol, 399.6 mg/g with glycidol, and 349.9 mg/g with 4-bromobutyronitrile.

  10. Signalling pathways involved in antitumoral effects of VIP in human renal cell carcinoma A498 cells: VIP induction of p53 expression.

    PubMed

    Vacas, Eva; Muñoz-Moreno, Laura; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2014-08-01

    Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K signalling and prevents tumour progression in clear renal cell carcinoma (RCC). Here we analyzed the signalling pathways that mediate such VIP effects by using human RCC A498 cells. The effects of treatment with 1 μM VIP and/or specific protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by cell adhesion assay, ELISA of VEGF165 and ROS production assays. Semiquantitative RT-PCR and western blot were performed to study p53 expression. VIP increased cell adhesion and ROS production, and decreased VEGF165 secretion through PI3K signalling. Moreover, VIP increased nuclear expression of tumour suppressor p53. VIP effects could be blocked by cell incubation with a specific p53 inhibitor, cyclin pifithrin-α hydrobromide (CPFT-αH). In conclusion, this study provides a p53-dependent mechanism by which VIP regulates cell proliferation in RCC development. It supports a potential usefulness of VIP in new therapies of RCC.

  11. Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V).

    PubMed

    El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

    2007-04-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at lambdamax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 microg mL-1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method. PMID:17142094

  12. Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.

    PubMed

    Tominaga, Takahiro; Ito, Hiroaki; Ishikawa, Yoichi; Iwata, Ren; Ishiwata, Kiichi; Furumoto, Shozo

    2016-03-01

    Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. PMID:26861736

  13. Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats.

    PubMed

    Heo, Yu-Mi; Shin, Mal-Soon; Kim, Su-Hyun; Kim, Tae-Wook; Baek, Sang-Bin; Baek, Seung-Soo

    2014-06-01

    Alzheimer's disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer's disease.

  14. The effects of different types of pre-training on the rat's retention performance in a swim-to-platform task following administration of scopolamine.

    PubMed

    Caldji, C; Vanderwolf, C H

    1996-10-01

    Previous research has found that centrally acting antimuscarinic drugs strongly impair the acquisition of a variety of learned behaviors in rats but have little effect on these same behaviors if training is given prior to drug treatment. We gave groups of rats different types of pre-training followed by treatment with scopolamine hydrobromide and subsequent testing on a simple swim-to-platform test. Factors such as practice in swimming without a platform to escape to, or learning to swim to a platform in a different apparatus or even to the test platform located in a different place did not protect the rats from the behavioral disruption produced by scopolamine. However, five training trials on the specific swim-to-platform task used in the retention test afforded almost complete protection against the effect of scopolamine. It appears that the protective effect of pre-training is highly specific and does not involve acquisition of some type of general rule which might survive antimuscarinic blockade.

  15. Polythiophene derivative on quartz resonators for miRNA capture and assay.

    PubMed

    Palaniappan, Al; Cheema, Jamal Ahmed; Rajwar, Deepa; Ammanath, Gopal; Xiaohu, Liu; Koon, Lim Seng; Yi, Wang; Yildiz, Umit Hakan; Liedberg, Bo

    2015-12-01

    A novel approach for miRNA assay using a cationic polythiophene derivative, poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrobromide] (PT), immobilized on a quartz resonator is proposed. The cationic PT enables capturing of all RNA sequences in the sample matrix via electrostatic interactions, resulting in the formation of PT-RNA duplex structures on quartz resonators. Biotinylated peptide nucleic acid (b-PNA) sequences are subsequently utilized for the RNA assay, upon monitoring the PT-RNA-b-PNA triplex formation. Signal amplification is achieved by anchoring avidin coated nanoparticles to b-PNA in order to yield responses at clinically relevant concentration regimes. Unlike conventional nucleic acid assay methodologies that usually quantify a specific sequence of RNA, the proposed approach enables the assay of any RNA sequence in the sample matrix upon hybridization with a PNA sequence complementary to the RNA of interest. As an illustration, successful detection of mir21, (a miRNA sequence associated with lung cancer) is demonstrated with a limit of detection of 400 pM. Furthermore, precise quantification of mir21 in plasma samples is demonstrated without requiring PCR and sophisticated instrumentation.

  16. Ritanserin-sensitive receptors modulate the prosocial and the anxiolytic effect of MDMA derivatives, DOB and PMA, in zebrafish.

    PubMed

    Ponzoni, Luisa; Sala, Mariaelvina; Braida, Daniela

    2016-11-01

    Little is known about the pharmacological effects of amphetamine derivatives. In the present study, the effect on social preference and anxiety-like behavior of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), in comparison with 3,4 methylenedioxymethamphetamine (MDMA) was investigated in zebrafish, an emerging model to study emotional behavior in an inexpensive and quick manner. DOB (0.05-2mg/kg), PMA (0.0005-2mg/kg) or MDMA (0.25-20mg/kg), given i.m. to adult zebrafish, progressively increased the time spent in the proximity of nacre fish picture in a social preference test. However, high doses were ineffective. Similarly, in the novel tank diving and light-dark tests the compounds elicited a progressive anxiolytic effect in terms of time spent in the upper half of the tank and in the light compartment, respectively. All the above effects were interpolated by symmetrical parabolas. The 5-HT2A/C antagonist ritanserin (0.025-2.5mg/kg) in association with the maximal effective dose of MDMA, DOB and PMA blocked both the social and anxiolytic effect. Taken together these findings demonstrate for the first time the prosocial and anxiolytic properties of DOB and PMA and focus on the mechanisms of their action through the serotonergic-like system suggesting a potential clinical application. PMID:27506653

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386

  18. Low-frequency assessment of airway and tissue mechanics in ventilated COPD patients.

    PubMed

    Lorx, András; Szabó, Barna; Hercsuth, Magdolna; Pénzes, István; Hantos, Zoltán

    2009-12-01

    Low-frequency forced oscillations have increasingly been employed to characterize airway and tissue mechanics separately in the normal respiratory system and animal models of lung disease; however, few data are available on the use of this method in chronic obstructive pulmonary disease (COPD). We studied 30 intubated and mechanically ventilated patients (COPD, n = 9; acute exacerbation of COPD, n = 21) during short apneic intervals at different levels of positive end-expiratory pressure (PEEP), with small-amplitude forced oscillations between 0.4 and 4.8 Hz. In 16 patients, measurements were made before and after inhalation of fenoterol hydrobromide plus ipratropium bromide (Berodual). Newtonian resistance and coefficients of tissue resistance (G) and elastance (H) were estimated from the respiratory system impedance (Zrs) data by model fitting. Apart from some extremely high Zrs data obtained primarily at relatively low PEEP levels, the model yielded a reasonable partitioning of the airway and tissue parameters, and the inclusion of further parameters did not improve the model performance. With increasing PEEP, Newtonian resistance and the ratio G/H decreased, reflecting the volume dependence of the airway caliber and the improved homogeneity of the lungs, respectively. Bronchodilation after the administration of Berodual was also associated with simultaneous decreases in G and H, indicating recruitment of lung units. In conclusion, the measurement of low-frequency Zrs can be accomplished in ventilated COPD patients during short apneic periods and offers valuable information on the mechanical status of the airways and tissues.

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, ABX-EGF, acetyldinaline, ACIDFORM, acyline, afeletecan hydrochloride, anecortave acetate, apolizumab, l-arginine hydrochloride, asimadoline, atazanavir sufate, atlizumab; BMS-181176, BMS-188667; CAB-175, carnosine, CDP-870, CEP-701, CEP-7055, CGC-1072, ChimeriVax-JE, ciclesonide, cilomilast, clofarabine, combretastatin A-4 phosphate, cryptophycin 52; Duloxetine hydrochloride; E-5564, eculizumab, elcometrine, emtricitabine, ENO, epratuzumab, eszopiclone, everolimus; Fampridine, flurbiprofen nitroxybutyl ester; Garenoxacin mesilate, gestodene, GI-181771, gimatecan, gomiliximab; Halofuginone hydrobromide, hGH, hLM609; ICA-17043, IL-1 receptor type II, IMC-1C11, iodine (I131) tositumomab, irofulven, ISAtx-247; J591; L-778123, lanthanum carbonate Lasofoxifene tartrate, LDP-02, LE-AON, leteprinim potassium, lintuzumab, liraglutide, lubiprostone, lumiracoxib, lurtotecan, LY-450108, LY-451395; MAb G250, magnesium sulfate, MDX-210, melatonin, 2-methoxy-estradiol, monophosphoryl lipid A; NM-3, nolpitantium besilate; Ocinaplon, olpadronic acid sodium salt, oral heparin; Palonosetron hydrochloride, pemetrexed disodium, PI-88, picoplatin, plevitrexed, polyphenon E, pramlintide acetate, pregabalin, prinomastat, pyrazoloacridine; Resiniferatoxin, rhEndostatin, roxifiban acetate; S-18886, siplizumab, sitaxsentan sodium, solifenacin succinate, SU-11248, SU-6668; Talampanel, TAPgen, testosterone transdermal gel, trabectedin; VEGF-2 gene therapy, visilizumab; ZD-6416, ZD-6474. PMID:12949633

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine. PMID:12224444

  1. Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats.

    PubMed

    Miczek, K A; Lau, P

    1975-06-19

    It has been postulated that behavioral inhibition due to punishment or extinction may be mediated by brain acetylcholine, and drugs which have disinhibitory action are thought to interact with this system. This notion was tested by comparing the effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption. Scopolamine hydrobromide (0.3, 0.5 mg/kg, i.p.), a centrally and peripherally acting antimuscarinic agent and physostigmine sulfate, (0.3 mg/kg, i.p.), a centrally and peripherally acting acetylcholinesterase inhibitor, lowered both non-punished and punishment suppressed water intake and lick rate, whereas their quaternary analogs which primarily act in the periphery, had no significant effect at comparable dose levels. Scopolamine and physostigmine suppressed punished water consumption at lower dose levels than nonpunished intake. In contrast, chlordiazepoxide (5.0, 10.0, 20.0 mg/kg, i.p.) enhanced punished as well as non-punished water intake. In a further experiment comparing punishment and extinction suppression, scopolamine and physostigmine did not affect punished or extinguished water intake; chlordiazepoxide (5.0, 10.0, 20.0 mg/kg) reliably increased punished, but not extinguished licking on the water nozzle. These results suggest (1) that scopolamine and chlordiazepoxide do not act via a common mechanism, and (2) that punishment and extinction suppression are not a pharmacological entity. PMID:1161984

  2. Preparation of a β-Cyclodextrin-Based Open-Tubular Capillary Electrochromatography Column and Application for Enantioseparations of Ten Basic Drugs

    PubMed Central

    Fang, Linlin; Yu, Jia; Jiang, Zhen; Guo, Xingjie

    2016-01-01

    An open-tubular capillary electrochromatography column was prepared by chemically immobilized β-cyclodextrin modified gold nanoparticles onto new surface with the prederivatization of (3-mercaptopropyl)-trimethoxysilane. The synthesized nanoparticles and the prepared column were characterized by transmission electron microscopy, scanning electron microscopy, infrared spectroscopy and ultraviolet visible spectroscopy. When the column was employed as the chiral stationary phase, no enantioselectivity was observed for ten model basic drugs. So β-cyclodextrin was added to the background electrolyte as chiral additive to expect a possible synergistic effect occurring and resulting in a better separation. Fortunately, significant improvement in enantioselectivity was obtained for ten pairs of drug enantiomers. Then, the effects of β-cyclodextrin concentration and background electrolyte pH on the chiral separation were investigated. With the developed separation mode, all the enantiomers (except for venlafaxine) were baseline separated in resolutions of 4.49, 1.68, 1.88, 1.57, 2.52, 2.33, 3.24, 1.63 and 3.90 for zopiclone, chlorphenamine maleate, brompheniramine maleate, dioxopromethazine hydrochloride, carvedilol, homatropine hydrobromide, homatropine methylbromide, venlafaxine, sibutramine hydrochloride and terbutaline sulfate, respectively. Further, the possible separation mechanism involved was discussed. PMID:26771454

  3. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    PubMed

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. PMID:27139517

  4. Effects of selected anticholinergics on acoustic startle response in rats.

    PubMed

    Sipos, M L; Burchnell, V; Galbicka, G

    2001-12-01

    The present study compared the effects of the anticholinergics aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide and trihexyphenidyl hydrochloride on acoustic startle response in rats. Peak startle amplitude, latency to peak startle amplitude and prepulse inhibition following 100- and 120-dB tones were recorded 15 min following drug administration in food-restricted rats. Aprophen, atropine, azaprophen, benactyzine, biperiden and scopolamine significantly increased peak startle amplitude and decreased latency to peak startle amplitude following 100-dB pulses. In contrast, only biperiden increased peak startle amplitude following 120-dB pulses, whereas atropine and trihexyphenidyl decreased latency to peak startle amplitude following 120-dB pulses. Benactyzine decreased prepulse inhibition following both 100- and 120-dB pulses, whereas both biperiden and scopolamine decreased prepulse inhibition following 120-dB pulses. Acoustic startle response measures were effective in differentiating the effects of anticholinergic compounds. The comparison of drug effects on the acoustic startle response may be useful in selecting efficacious anticholinergic drug therapies with a minimal range of side-effects. In addition, these data may be useful in down-selecting the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests. PMID:11920928

  5. Oxidation of pharmaceutically active compounds by a ligninolytic fungal peroxidase.

    PubMed

    Eibes, Gemma; Debernardi, Gianfranco; Feijoo, Gumersindo; Moreira, M Teresa; Lema, Juan M

    2011-06-01

    Pharmaceuticals are an important group of emerging pollutants with increasing interest due to their rising consumption and the evidence for ecotoxicological effects associated to trace amounts in aquatic environments. In this paper, we assessed the potential degradation of a series of pharmaceuticals: antibiotics (sulfamethoxazole), antidepressives (citalopram hydrobromide and fluoxetine hydrochloride), antiepileptics (carbamazepine), anti-inflammatory drugs (diclofenac and naproxen) and estrogen hormones (estrone, 17β-estradiol, 17α-ethinylestradiol) by means of a versatile peroxidase (VP) from the ligninolytic fungus Bjerkandera adusta. The effects of the reaction conditions: VP activity, organic acid concentration and H(2)O(2) addition rate, on the kinetics of the VP based oxidation system were evaluated. Diclofenac and estrogens were completely degraded after only 5-25 min even with a very low VP activity (10 U l(-1)). High degradation percentages (80%) were achieved for sulfamethoxazole and naproxen. Low or undetectable removal yields were observed for citalopram (up to 18%), fluoxetine (lower than 10%) and carbamazepine (not degraded). PMID:20972884

  6. Sofosbuvir (Sovaldi°). Active against hepatitis C virus, but evaluation is incomplete .

    PubMed

    2015-01-01

    About 50% of patients with chronic hepatitis C virus (HCV) genotype 1 infection have a sustained virological response to a 48-week course of the peginterferon alfa + ribavirin combination. Adding a viral protease inhibitor to this combination for 12 to 32 weeks enhances antiviral effects but increases the risk of serious adverse effects. Between 70% and 80% of patients with HCV genotype 2 or 3 infection have a sustained virological response to a 24-week course of the peginterferon alfa + ribavirin combination. Sofosbuvir, a nucleotide inhibitor of viral (or HCV) NS5B RNA polymerase,has been authorised in the European Union for the treatment of chronic hepatitis C, in combination with other drugs. Despite the inclusion of several clinical trials, initial evaluation of sofosbuvir provides only a minimal picture of the harm-benefit balance. Sofosbuvir has not been compared directly with viral protease inhibitors in randomised clinical trials. In a trial involving 121 patients with HCV genotype 1 infection, the sustained viral response rate was 90% when sofosbuvir was added to the peginterferon alfa + ribavirin combination for 12 weeks, versus about 60% with peginterferon alfa + ribavirin alone. In a randomised, unblinded, noninferiority trial in 527 previously untreated patients with HCV genotype 2 or 3 infection, sofosbuvir + ribavirin combination therapy given for 12 weeks had virological efficacy similar to peginterferon alfa-2a + ribavirin combination therapy given for 24 weeks. However, there were signs that sofosbuvir might be less effective against HCV genotype 3. In an uncontrolled study of 114 patients with HCV genotype 1 infection who could not receive peginterferon alfa, the sofosbuvir + ribavirin combination yielded sustained virological responses in about 75% of cases. Similar results were obtained in a double-blind, placebo-controlled trial in 280 patients with HCV genotype 2 or 3 infection. Too few cases of HCV genotype 4, 5 or 6 infection were included

  7. Comparative efficacy, pharmacokinetic, pharmacodynamic activity, and interferon stimulated gene expression of different interferon formulations in HIV/HCV genotype-1 infected patients.

    PubMed

    Osinusi, Anu; Bon, Dimitra; Nelson, Amy; Lee, Yu-Jin; Poonia, Seerat; Shivakumar, Bhavana; Cai, Shu Yi; Wood, Brad; Haagmans, Bart; Lempicki, Richard; Herrmann, Eva; Sneller, Michael; Polis, Michael; Masur, Henry; Kottilil, Shyam

    2014-02-01

    The effect of different formulations of interferon on therapeutic response in patients coinfected with HIV and HCV is unclear. In this study, the safety, tolerability, viral kinetics (VK) modeling and host responses among HIV/HCV coinfected patients treated with pegylated-IFN or albinterferon alfa-2b (AlbIFN) with weight-based ribavirin were compared. Three trials treated 57 HIV/HCV coinfected genotype-1 patients with PegIFN alfa-2b (1.5 µg/kg/week) (n = 30), PegIFN alfa-2a (180 µg/week) (n = 10), and AlbIFN (900 µg/q2week) (n = 17) in combination with weight-based ribavirin (RBV). HCV RNA, safety labs, and interferon stimulated gene expression (ISG) was evaluated. Adverse events were documented at all study visits. HCV viral kinetics using a full pharmacokinetic/pharmacodynamic model was also evaluated. Baseline patient characteristics were similar across the three studies. All three formulations exhibited comparable safety and tolerability profiles and efficacy. VK/PK/PD parameters for all three studies as measured by mean efficiency and rate of infected cell loss were similar between the three groups. Host responses (ISG expression and immune activation markers) were similar among the three groups. All three regimens induced significant ISG at week 4 (P < 0.05) and ISG expression strongly correlated with therapeutic response (r = 0.65; P < 0.01). In summary, a comprehensive analysis of responses to three different interferon formulations in HIV/HCV coinfected patients demonstrated similar effects. Notably, interferon-based therapy results in a blunted host response followed by modest antiviral effect in HIV/HCV coinfected patients. This suggests that future treatment options that do not rely on host immune responses such as direct antiviral agents would be particularly beneficial in these difficult to treat patients. PMID:24166150

  8. [Aicardi-Goutieres syndrome due to mutation of the IFIH1 gene with pontine involvement. A case report].

    PubMed

    Florido-Rodriguez, A; Eiris-Punal, J; Barros-Angueira, F; Toledo-Bravo de Laguna, L; Santana-Artiles, A; Sebastian-Garcia, I; Santana-Rodriguez, A; Cabrera-Lopez, J C

    2016-10-01

    Introduccion. El sindrome de Aicardi-Goutieres es una rara encefalopatia subaguda progresiva de inicio precoz –generalmente en el primer año de vida– caracterizada por retraso psicomotor, microcefalia, alteraciones en la sustancia blanca cerebral, calcificaciones intracraneales, pleocitosis y niveles elevados de interferon alfa en el liquido cefalorraquideo. Asocia un incremento en la expresion de los genes estimulados por interferon en la sangre periferica, hecho conocido como interferon signature. Los niveles de genes estimulados por interferon se han postulado como un buen biomarcador, pues se mantienen elevados en la sangre periferica en el tiempo y son mas sensibles, en comparacion con las determinaciones de interferon alfa y neopterinas en el liquido cefalorraquideo, las cuales descienden a partir del año de vida. Hasta la fecha se han descrito mutaciones en siete genes que sobreestimulan la via del interferon alfa, y el ultimo en descubrirse ha sido el IFIH1 (interferon induced with helicase C domain 1), con un patron de herencia autosomico dominante. Caso clinico. Se presenta el primer caso descrito en la bibliografia hispana debido a mutacion de novo en el gen IFIH1. Se expone el cuadro clinico, los estudios realizados y la revision de los aspectos clinicos, neurorradiologicos y geneticos. Conclusiones. La herencia de las mutaciones descritas para el sindrome de Aicardi-Goutieres era clasicamente autosomica recesiva, pero estos hallazgos muestran que mutaciones autosomicas dominantes en el gen IFIH1 pueden causar la enfermedad. Como hallazgo de neuroimagen no descrito previamente, presenta una lesion de encefalomalacia quistica en la protuberancia.

  9. [Coagulation disorders in the intensive care unit - what is new?].

    PubMed

    Hart, Christina; Schmid, Stephan

    2016-06-01

    The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life-threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa-inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels. PMID:27254626

  10. Hypophosphatasia - pathophysiology and treatment

    PubMed Central

    Millán, José Luis; Plotkin, Horacio

    2013-01-01

    English Summary Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) in the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). The disease has been classified according to patient age when the first signs and symptoms manifest; i.e., perinatal, infantile, childhood, adult HPP. Other types include odonto HPP and perinatal benign. Babies with the perinatal/infantile forms of HPP often die with severe rickets and respiratory insufficiency and sometimes hypercalcemia and vitamin B6-responsive seizures. The primary biochemical defect in HPP is a deficiency of TNAP activity that leads to elevated circulating levels of substrates, in particular inorganic pyrophosphate (PPi), a potent calcification inhibitor. To-date, the management of HPP has been essentially symptomatic or orthopedic. However, enzyme replacement therapy with mineral-targeting TNAP (sALP-FcD10, also known as ENB-0040 or asfotase alfa) has shown promising results in a mouse model of HPP (Alpl−/− mice). Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acellular cementum, and enamel defects in this model of severe HPP. Clinical trials using mineral-targeting TNAP in children 3 years of age or younger with life-threatening HPP was associated with healing of the skeletal manifestations of HPP as well as improved respiratory and motor function. Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. Enzyme replacement therapy with asfotase alfa has to-date been successful in patients with life-threatening HPP. PMID:25254037

  11. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)

    PubMed Central

    Hoffmann, B; d Garcia; Mehta, A; Beck, M; Widmer, U; Ricci, R; on, b

    2005-01-01

    Background: Fabry disease is an X linked lysosomal storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A. This leads to accumulation of globotriaosylceramide in nearly all tissues, including the blood vessels, kidney, myocardium, and nervous system. Symptoms often begin in childhood and include acroparaesthesia, with burning or tingling pain that spreads from the extremities to more proximal sites. Aims: This study set out to evaluate pain and its influence on quality of life in patients with Fabry disease receiving enzyme replacement therapy (ERT) with agalsidase alfa. Methods: Data were obtained from the Fabry Outcome Survey. Pain was measured using the Brief Pain Inventory (BPI), and health-related quality of life (HRQoL) was documented with the European Quality of Life Questionnaire (EQ-5D). Results: The mean (SD) score for "pain at its worst" on the BPI prior to ERT was 5.1 (2.7). One year after commencement of ERT, this had improved by 0.5, and improved by a further 0.6 after 2 years (p<0.05). Similar statistically significant improvements were seen for "pain on average" and "pain now" after 2 years of ERT. The mean HRQoL utility score prior to ERT was 0.66 (0.32). After 12 months of treatment with agalsidase alfa, this had improved to 0.74 (0.26; p<0.05); this improvement was maintained after 2 years. Conclusions: ERT with agalsidase alfa significantly reduces pain and improves quality of life in patients with Fabry disease. PMID:15744039

  12. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  14. Experiments with a small behaviour controlled planetary rover

    NASA Technical Reports Server (NTRS)

    Miller, David P.; Desai, Rajiv S.; Gat, Erann; Ivlev, Robert; Loch, John

    1993-01-01

    A series of experiments that were performed on the Rocky 3 robot is described. Rocky 3 is a small autonomous rover capable of navigating through rough outdoor terrain to a predesignated area, searching that area for soft soil, acquiring a soil sample, and depositing the sample in a container at its home base. The robot is programmed according to a reactive behavior control paradigm using the ALFA programming language. This style of programming produces robust autonomous performance while requiring significantly less computational resources than more traditional mobile robot control systems. The code for Rocky 3 runs on an eight bit processor and uses about ten k of memory.

  15. Identification of recombinant human EPO variants in greyhound plasma and urine by ELISA, LC-MS/MS and western blotting: a comparative study.

    PubMed

    Timms, Mark; Steel, Rohan; Vine, John

    2016-02-01

    The recombinant human erythropoietins epoetin alfa (Eprex®), darbepoetin (Aranesp®) and methoxy polyethylene glycol-epoetin beta (Mircera®) were administered to greyhounds for 7, 10 and 14 days respectively. Blood and urine samples were collected and analysed for erythropoietin by ELISA, LC-MS/MS and western blotting. Limits of confirmation in plasma for western blotting and LC-MS/MS methods ranged from a low of 2.5mIU/mL, and closely matched the sensitivity of ELISA screening. PMID:26290355

  16. Biological agents: investigation into leprosy and other infectious diseases before indication*

    PubMed Central

    Antônio, João Roberto; Soubhia, Rosa Maria Cordeiro; Paschoal, Vania Del Arco; Amarante, Carolina Forte; Travolo, Ana Regina Franchi

    2013-01-01

    Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil. PMID:24346871

  17. Diffraction and forward physics results of the ATLAS experiment from the Run I

    SciTech Connect

    Taševský, Marek

    2015-04-10

    Various aspects of forward physics have been studied by the ATLAS collaboration using data from Run I at the LHC. In this text, main results of four published analyses are summarized, all based on data from proton-proton collisions at √(s)=7 TeV collected in 2010 or 2011. Two analyses deal with the diffractive signature, one based on single-sided events, the other on large rapidity gaps in soft events. In addition, a recent measurement of the total pp cross section using the ALFA subdetector and a recent study of higher-order QCD effects using a jet veto are discussed.

  18. Diffraction and Forward Physics in ATLAS: results and perspectives

    NASA Astrophysics Data System (ADS)

    Bruschi, M.

    2015-03-01

    The present and future potential of ATLAS for diffraction and forward physics is presented. As recent results the rapidity gap cross section and elastic and total pp cross sections are reported. The upgrade project AFP is presented and it is shown how it will complement the ALFA acceptance for diffractive physics in measurements taken with β*=90 m LHC beam optics. Moreover, the AFP detector will guarantee good acceptance on diffractive events also during normal running conditions allowing to improve the ATLAS detector performances. If in addition, a high luminosity program will be feasible, AFP might be fundamental for potential discoveries with extra dimensions being one example.

  19. Lube oil centrifuge saves Odeco $360,000/year

    SciTech Connect

    Closs, D.E.

    1983-05-01

    Purifying centrifuges were installed in the offshore drilling operation diesel engines of the Odeco Co. of New Orleans. The centrifuges extend filter life fourfold, eliminate the need to change oil at all, and defer the need for costly overhauls indefinitely. The Alfa-Laval built centrifuges were placed on 23 mobile rigs that Odeco has working in the Gulf of Mexico, and they paid for their cost twice over during the first year of operation. Originally, a lubricant centrifuge was tested aboard the Ocean Tempest. The results were so remarkable that similar installations were placed on all other vessels in the domestic drilling division.

  20. Noninvasive sensors in critical care medicine: near-infrared spectroscopy for the detection of altered microvascular blood flow in severe sepsis and septic shock

    NASA Astrophysics Data System (ADS)

    Walz, J. Matthias; Soller, Babs; Soyemi, Olusola; Yang, Ye; Landry, Michelle; Heard, Stephen O.

    2006-10-01

    It is estimated that 750,000 cases of severe sepsis occur in the United States annually, at least 225,000 of which are fatal, resulting in significant utilization of healthcare resources and expenses. Significant progress in the understanding of pathophysiology and treatment of this condition has been made lately. Among the newer treatment strategies for critically ill patients are the administration of early goal directed therapy, and Recombinant Human Activated Protein C (Drotrecogrin alfa (activated) [DTAA]) for severe sepsis. However, mortality remains unacceptably high.

  1. Infasurf and Curosurf: Theoretical and Practical Considerations with New Surfactants

    PubMed Central

    Nguyen, Thuy N.; Cunsolo, Stephanie M.; Gal, Peter; Ransom, J. Laurence

    2003-01-01

    Type II pneumocytes, normally responsible for surfactant production and release, are insufficiently formed and differentiated in the premature infant born before 34 weeks' gestation. Without an adequate amount of pulmonary surfactant, alveolar surface tension increases, leading to collapse and decreased lung compliance. Pulmonary surfactants are naturally occurring substances made of lipids and proteins. They lower surface tension at the interface between the air in the lungs, specifically at the alveoli, and the blood in the capillaries. This review examines the relative benefits of the two most recently marketed surfactants, calfactan (Infasurf) and poractant alfa (Curosurf). PMID:23300398

  2. Biological agents: investigation into leprosy and other infectious diseases before indication.

    PubMed

    Antônio, João Roberto; Soubhia, Rosa Maria Cordeiro; Paschoal, Vania Del Arco; Amarante, Carolina Forte; Travolo, Ana Regina Franchi

    2013-01-01

    Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil. PMID:24346871

  3. Evaluation of the metal binding sites in a recombinant coagulation factor VIII identifies two sites with unique metal binding properties.

    PubMed

    Svensson, Lars Anders; Thim, Lars; Olsen, Ole Hvilsted; Nicolaisen, Else Marie

    2013-06-01

    Coagulation factor VIII is a glycosylated, non-covalent heterodimer consisting of a heavy chain (A1-A2-B domains) and a light chain (A3-C1-C2 domains). The association of the chains, and the stability and function of the dimer depend on the presence of metal ions. We applied X-ray fluorescence, X-ray crystallographic structure determination with anomalous signals at different wavelengths, and colorimetric measurements to evaluate the metal binding sites in a recombinant factor VIII molecule, turoctocog alfa. We identified a metal binding site in domain A3 dominated by Cu(+) binding and a site in domain A1 dominated by Zn(2+) binding.

  4. Recent advances in the treatment of orthostatic hypotension

    NASA Technical Reports Server (NTRS)

    Robertson, D.; Davis, T. L.

    1995-01-01

    Orthostatic hypotension is a fall in blood pressure on standing that causes symptoms of dizziness, visual changes, and discomfort in the head and neck. The goal of treatment is the improvement of the patient's functional capacity, rather than a target blood pressure. For treatment to be successful, it must be individualized. Non-pharmalogic interventions include carefully managed exercise, scheduled activities, and monitoring of the environmental temperature. Agents such as fludrocortisone, midodrine, and epoetin alfa offer successful pharmacologic interventions. Although these measures ease the symptoms of orthostatic hypotension, current approaches neither reverse nor stabilize the disease process in autonomic disorders.

  5. Influence of thin porous Al{sub 2}O{sub 3} layer on aluminum cathode to the H{sub a}lpha line shape in glow discharge

    SciTech Connect

    Steflekova, V.; Sisovic, N. M.; Konjevic, N.

    2009-06-01

    The results of the Balmer alfa line shape study in a plane cathode-hollow anode Grimm discharge with aluminum (Al) cathode covered with thin layer of porous Al{sub 2}O{sub 3} are presented. The comparison with same line profile recorded with pure Al cathode shows lack of excessive Doppler broadened line wings, which are always detected in glow discharge with metal cathode. The effect is explained by the lack of strong electric field in the cathode sheath region, which is missing in the presence of thin oxide layer in, so called, spray discharge.

  6. Treating hepatitis C - what's new?

    PubMed

    Thompson, Alex J; Holmes, Jacinta A

    2015-12-01

    Chronic hepatitis C infection causes cirrhosis, liver failure and hepatocellular carcinoma, and is the most common indication for liver transplantation. Hepatitis C is curable and complications can be prevented. Until recently, treatment regimens involved peginterferon alfa. Although effective, their widespread use is limited by treatment-related toxicity. A number of direct-acting drugs for hepatitis C, such as sofosbuvir, have recently been developed and target multiple steps in the viral life cycle. These drugs are used in combination in interferon-free regimens. Short courses are highly effective with minimal toxicity. PMID:26843711

  7. VizieR Online Data Catalog: Dimethyl sulfide laboratory um, mm & FIR spectra (Jabri+, 2016)

    NASA Astrophysics Data System (ADS)

    Jabri, A.; Nguyen, H. V. L.; Mouhib, H.; Tchana, F. K.; Manceron, L.; Stahl, W.; Kleiner, I.

    2016-02-01

    DMS was purchased from Alfa Aesar GmbH & Co KG, Karlsruhe, Germany and used without further purification. The microwave spectrum was measured in the frequency range 2-40GHz using two Molecular Beam Fourier Transform MicroWave (MB-FTMW) spectrometers in Aachen, Germany. The millimeter spectrum was recorded in the 50-110GHz range. The FIR spectrum was measured for the first time at high resolution using the FT spectrometer and the newly built cryogenic cell at the French synchrotron SOLEIL. (3 data files).

  8. Advancing chronic kidney disease care: new imperatives for recognition and intervention.

    PubMed

    Szromba, Charlotte; Thies, Mary Ann; Ossman, Sherry Smith

    2002-12-01

    Chronic kidney disease (CKD) affects over 6.2 million people in the U.S. and most commonly results from diabetes and/or hypertension. Patients with CKD have an increased risk of anemia and hypertension. Anemia occurs early in CKD and can be effectively treated with epoetin alfa. Hypertension can be managed with lifestyle modifications and medications. Nurses play a vital role in managing these patients by providing early CKD/anemia screening and intervention, education, patient monitoring, and support for patients and caregivers. PMID:12596604

  9. Current Results at PALFA Pulsar Survey at Arecibo Observatory

    NASA Astrophysics Data System (ADS)

    Beroiz, Martin; Stovall, K.; Jenet, F.; Cordes, J.; Lorimer, D.; Backer, D.; PALFA Consortium

    2010-01-01

    We present the current progress on the PALFALFA (Pulsar-ALFALFA) survey recently started at the Arecibo Radio Observatory. PALFALFA enhances the ALFALFA (Arecibo Legacy Fast ALFA) extragalactic HI survey by adding a commensal real-time pulsar/radio transient search pipe-line. The current analysis pipe-line runs on an 8 core (2.3 GHz) G5 Macpro at the observatory. It incorporates the PRESTO periodicity search tools together with software developed at University of Texas at Brownsville for radio transient detection. In this poster we present results, statistics, and algorithms used in the survey.

  10. Anti-erythropoietin antibodies followed by endogenous erythropoietin production in a dialysis patient.

    PubMed

    Mattison, Parnell; Upadhyay, Kiran; Wilcox, Jennifer E; Moudgil, Asha; Silverstein, Douglas M

    2010-05-01

    We present a case of a young girl with end-stage renal disease secondary to anti-glomerular basement membrane disease who was receiving maintenance peritoneal dialysis and developed pure red cell aplasia secondary to anti-erythropoietin (EPO) antibodies. This occurred 13 months after the initiation of EPO alfa therapy for anemia. Initially, the patient required intermittent red blood cell transfusions. After immunosuppressive therapy had been initiated with corticosteroids and cyclosporine, the EPO antibody levels decreased precipitously, associated with an increased level of endogenous EPO production. For the following 6 months, the patient maintained adequate (>10 g/dL) hemoglobin levels and did not require red cell transfusions.

  11. The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy

    PubMed Central

    Varbobitis, Ioannis; Papatheodoridis, George V.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed. PMID:27729632

  12. New Az/El mount for Haystack Observatory's Small Radio Telescope kit

    NASA Astrophysics Data System (ADS)

    Cobb, M. L.

    2005-12-01

    The Small Radio Telescope (SRT) kit was designed by Haystack Observatory as part of their educational outreach effort. The SRT uses a custom designed FFT based radio spectrometer receiver with a controller to position a 2.3m dish to make various radio astronomy observations including the 21 cm spin flip line of atomic hydrogen. Because there is no sizable commercial market for a two dimensional mount for dishes of this size, finding an appropriate provider as been a recurring problem for the project. Originally, the kit used a modified motor mount from Kaultronics called the H180. Two of these motors were combined by a specially designed adaptor to allow motion in azimuth and elevation. When Kaultronics was bought out by California Amplifier they discontinued production of the H180. The next iteration used a compact unit called the alfa-spid which was made in Germany and imported through Canada. The alfa-spid was designed to point various ham radio antennas and proved problematic with 2.3m dishes. Most recently the CASSI (Custom Astronomical Support Services, Inc.) corporation has designed and certified a robust Az/El mount capable of supporting dishes up to 12 feet (3.6m) with 100 MPH wind loads. This paper presents the design and operating characteristics of the new CASSI mount. The CASSI mount is now shipped with the SRT kit and should serve the project well for the foreseeable future.

  13. Comparative study on mannose 6-phosphate residue contents of recombinant lysosomal enzymes.

    PubMed

    Togawa, Tadayasu; Takada, Masaru; Aizawa, Yoshiaki; Tsukimura, Takahiro; Chiba, Yasunori; Sakuraba, Hitoshi

    2014-03-01

    As most recombinant lysosomal enzymes are incorporated into cells via mannose 6-phosphate (M6P) receptors, the M6P content is important for effective enzyme replacement therapy (ERT) for lysosomal diseases. However, there have been no comprehensive reports of the M6P contents of lysosomal enzymes. We developed an M6P assay method comprising three steps, i.e., acid hydrolysis of glycoproteins, derivatization of M6P, and high-performance liquid chromatography, and determined the M6P contents of six recombinant lysosomal enzymes now available for ERT and one in the process of development. The assay is easy, specific, and reproducible. The results of the comparative study revealed that the M6P contents of agalsidase alfa, agalsidase beta, modified α-N-acetylgalactosaminidase, alglucosidase alfa, laronidase, idursulfase, and imiglucerase are 2.1, 2.9, 5.9, 0.7, 2.5, 3.2, and <0.3 mol/mol enzyme, respectively. The results were correlated with those of the biochemical analyses previously performed and that of the binding assay of exposed M6P of the enzymes with the domain 9 of the cation-independent M6P receptor. This assay method is useful for comparison of the M6P contents of recombinant lysosomal enzymes for ERT. PMID:24439675

  14. Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems.

    PubMed

    Tekoah, Yoram; Tzaban, Salit; Kizhner, Tali; Hainrichson, Mariana; Gantman, Anna; Golembo, Myriam; Aviezer, David; Shaaltiel, Yoseph

    2013-01-01

    The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution. PMID:23980545

  15. High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin.

    PubMed

    Waizmann, Michael; Ackermann, Grit

    2010-06-01

    This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon-induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once-daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting. PMID:20362408

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-12-01

    [Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib

  17. [Factors related to residual renal function loss in patients in peritoneal dialysis].

    PubMed

    Munguía-Miranda, Catarina; Ventura-García, María de Jesús; Ávila-Díaz, Marcela; Orihuela-Rodríguez, Oscar; Paniagua-Sierra, José Ramón

    2015-01-01

    Introducción: la conservación de la función renal residual (FRR) en los pacientes en diálisis peritoneal (DP) tiene una clara influencia sobre la calidad de vida, independientemente de que su preservación ha demostrado influir en la mayor supervivencia de los pacientes. El objetivo del presente estudio fue conocer los factores relacionados con pérdida de la FRR en un grupo de pacientes prevalentes en diálisis peritoneal continua ambulatoria (DPCA). Métodos: se trata de un estudio de análisis de resultados secundarios. Se incluyeron 43 adultos con diabetes tipo 2 (DT2), con FRR conservada, a quienes se les dio seguimiento durante un año. Resultados: los factores relacionados con la pérdida de la FRR fueron: género masculino (p = 0.042), presión arterial sistólica (p = 0.009) y diastólica (p = 0.006), hemoglobina (p = 0.008), aclaramiento peritoneal de creatinina (p = 0.014), ultrafiltración (p = 0.017), niveles de factor de necrosis tumoral alfa (FNT–alfa) en plasma (p = 0.022) y dializado (p = 0.008). Conclusiones: es importante conocer los factores relacionados con pérdida de la FRR en nuestros pacientes para evitar la pérdida gradual de la misma y sus implicaciones